ST elevation myocardial infarction glycoprotein IIbIIIa inhibition: Difference between revisions

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{{Infobox_Disease |
__NOTOC__
  Name          = Myocardial infarction|
{{ST elevation myocardial infarction}}
  Image          = |
{{CMG}}
  Caption        = |
 
  DiseasesDB    = 8664 |
==Overview==
  ICD10          = {{ICD10|I|21||i|20}}-{{ICD10|I|22||i|20}} |
===Other Antiplatelet Agents Including Aspirin and Thienopyridines===
  ICD9          = {{ICD9|410}} |
There is clear data demonstrating the benefits of the antiplatelets [[aspirin]]<ref name="pmid2899772">{{cite journal |author= |title=Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group |journal=[[Lancet]] |volume=2 |issue=8607 |pages=349–60 |year=1988 |month=August |pmid=2899772 |doi= |url= |issn= |accessdate=2010-06-30}}</ref> and thienopyridenes <ref name="pmid16271642">{{cite journal |author=Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, Collins R, Liu LS |title=Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial |journal=[[Lancet]] |volume=366 |issue=9497 |pages=1607–21 |year=2005 |month=November |pmid=16271642 |doi=10.1016/S0140-6736(05)67660-X |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(05)67660-X |issn= |accessdate=2010-06-30}}</ref> in the management of patients with ST elevation MI treated with [[fibrinolytic]] administration. The benefits of [[clopidogrel]] vs [[placebo]] in patients undergoing [[primary angioplasty]] have not been established in randomized trials, although non-randomized registry data is consistent with a benefit of clopidogrel in this setting.  The benefit of aspirin plus thienopyridine therapy versus aspirin monotherapy alone could be difficult to establish in randomized trials given that the majority of STEMI patients are treated with a stent which in turn obviates chronic thienopyridine treatment.  Despite the required chronic thienopyridine therapy following stent placement, the slower onset of action of oral thienopyridines relative to that of parenteral antiplatelet agents such as glycoprotein IIb/IIIa inhibitors raises important questions as to the acute / early benefits of glycoprotein IIb/IIIa inhibitors versus thienopyridines. Furthermore, the optimal timing of thienopyridine therapy in primary PCI is not well established. In so far a few patients undergo coronary artery bypass grafting (CABG) surgery urgently in the setting of STEMI, the need to define the anatomy prior to theinopyridine administration may not be as compelling as it is in the setting of stable angina, unstable angina and non-ST elevation MI.
  ICDO          = |
 
  OMIM          = |
Current guidelines recommend pre-loading with 300 to 600 mg of clopidogrel in the primary PCI setting. Again, it should be emphasized that this is not based upon randomized trial data enrolling STEMI patients undergoing primary PCI, but rather from data originating from non-randomized subgroup analyses and registries. One registry demonstrated that pre-loading with clopidogrel in the setting of STEMI was associated with a 2.2 fold improvement in normal [[TIMI myocardial perfusion grade]] 3 (O.R. 1.2-3.9, p=0.01) was well as a reduced risk of [[recurrent MI]] (0% vs 3.2%, respectively, p= 0.04) <ref>Lev EI, Kornowski R, Vaknin-Assa H, Brosh D, Fuchs S, Battler A, Assali A.. Effect of clopidogrel pretreatment on angiographic and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-elevation acute myocardial infarction. Am J Cardiol. 2008;101(4):435-9.</ref>.  In a subgroup of 2707 patients managed with primary [[PCI]] in the Acute Coronary Syndromes (ACOS) registry, 1 year mortality was significantly reduced among patients treated with aspirin plus clopidogrel versus aspirin alone (OR 0.38, 95% CI 0.23-0.62]. It should be noted that this data is limited by the fact that neither the loading dose nor timing of clopidogrel were reported <ref> Zeymer U, Gitt AK, Jünger C, Heer T, et al. Effect of clopidogrel on 1-year mortality in hospital survivors of acute ST-segment elevation myocardial infarction in clinical practice. Eur Heart J. 2006;27(22):2661-6.</ref>. It should also be realized that in registries, clopidogrel administration is often a surrogate or a marker of the use of a stent, and it is not clear whether the benefit was mediated by the stent or by the clopidogrel.  Finally, Gibson et al in a substudy from CLARITY have demonstrated that non-emergent PCI after [[fibrinolytic]] therapy was associated with improved [[mortality]] among patients randomized to clopidogrel (OR 0.34, 95% CI 0.13-0.92, P = .034) but not placebo (OR 1.41, 95% CI 0.63-3.19, P = .40, interaction P = .028)<ref name="pmid18082504">{{cite journal |author=Gibson CM, Murphy SA, Pride YB, Kirtane AJ, Aroesty JM, Stein EB, Ciaglo LN, Southard MC, Sabatine MS, Cannon CP, Braunwald E |title=Effects of pretreatment with clopidogrel on nonemergent percutaneous coronary intervention after fibrinolytic administration for ST-segment elevation myocardial infarction: a Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 study |journal=[[American Heart Journal]] |volume=155 |issue=1 |pages=133–9 |year=2008 |month=January |pmid=18082504 |doi=10.1016/j.ahj.2007.08.034 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-8703(07)00770-3 |issn= |accessdate=2010-06-30}}</ref>.
  MedlinePlus    = 000195 |
 
  eMedicineSubj  = med |
===Glycoprotein IIb/IIIa Inhibition===
  eMedicineTopic = 1567 |
Glycoprotein IIb/IIIa inhibitors are a third class of antiplatelet agents that have, in contrast to aspirin and clopidogrel, been studied extensively in the setting of STEMI treated with [[primary PCI]]. Meta analyses of randomized trial data do support a clinical event reduction (including a strong trend toward a mortality reduction) among STEMI patients treated with GPIIb/IIIa inhibitors <ref name="pmid15265852">{{cite journal |author=Montalescot G, Borentain M, Payot L, Collet JP, Thomas D |title=Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis |journal=[[JAMA : the Journal of the American Medical Association]] |volume=292 |issue=3 |pages=362–6 |year=2004 |month=July |pmid=15265852 |doi=10.1001/jama.292.3.362 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15265852 |issn= |accessdate=2010-06-30}}</ref><ref name="pmid17251257">{{cite journal |author=Montalescot G, Antoniucci D, Kastrati A, Neumann FJ, Borentain M, Migliorini A, Boutron C, Collet JP, Vicaut E |title=Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients' data with long-term follow-up |journal=[[European Heart Journal]] |volume=28 |issue=4 |pages=443–9 |year=2007 |month=February |pmid=17251257 |doi=10.1093/eurheartj/ehl472 |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=17251257 |issn= |accessdate=2010-06-30}}</ref>. In contrast to primary PCI, there is no clinical benefit of GPIIb/IIIa inhibition when added to the administration of a full dose of a fibrinolytic agent when co-administered at the time of presentation with STEMI.  This combination is clearly associated with increased [[bleeding]], particularly in the elderly <ref name="pmid11425410">{{cite journal |author=Topol EJ |title=Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial |journal=[[Lancet]] |volume=357 |issue=9272 |pages=1905–14 |year=2001 |month=June |pmid=11425410 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673600050595 |issn= |accessdate=2010-06-30}}</ref>.  The benefit of glycoprotein IIb/IIIa administration in the cardiac catheterization laboratory several hours after fibrinolytic administration is supported by non-randomized observational data <ref> Roe MT, Giugliano RP, Tuttle R, Hasselbad V, Murphy SA, Antman EM, Ohman EM, Harrington RA, Granger CB, Mahaffey KW, Cannon CP, Lincoff AM, Gibson CM, Armstrong PW, van de Werf FJ, Califf RM, Topol EJ, Braunwald E. Safety of Adjunctive Glycoprotein IIb/IIIa Blockade During Rescue/Early Percutaneous Coronary Intervention Following Full-Dose Fibrinolytic Therapy for Acute Myocardial Infarction. J Am Coll Cardiol 2003;41(6 Suppl A):332A.</ref><ref name="pmid16446517">{{cite journal |author=Gruberg L, Suleiman M, Kapeliovich M, Hammerman H, Grenadier E, Boulus M, Amikam S, Markiewicz W, Beyar R |title=Glycoprotein IIb/IIIa inhibitors during rescue percutaneous coronary intervention in acute myocardial infarction |journal=[[The Journal of Invasive Cardiology]] |volume=18 |issue=2 |pages=59–62 |year=2006 |month=February |pmid=16446517 |doi= |url= |issn= |accessdate=2010-06-30}}</ref>. 
  eMedicine_mult = {{eMedicine2|emerg|327}} {{eMedicine2|ped|2520}} |
  MeshID        = |
}}
{{SI}}
{{WikiDoc Cardiology Network Infobox}}


{{CMG}}
There are several clinical questions regarding GP IIb/IIIa inhibition in the setting of STEMI that have not been definitively resolved in randomized trials:
#What is the optimal timing of GP IIb/IIIa inhibitors in STEMI? Is it before cardiac catheterization which may improve patency on arrival to the cardiac catheterization laboratory or is at the time of percutaneous coronary intervention (PCI)?
#What is the optimal route of GP IIb/IIIa inhibitors in STEMI? Is it via the intravenous route early, or via the intracoronary route once the anatomy has been defined.
#What is the optimal duration of GP IIb/IIIa inhibition? Longer durations of infusion may be associated with greater efficacy but also with more bleeding.
#What is the role of GP IIb/IIIa inhibitors in STEMI in the context of [[bivalirudin]] therapy?
#What is the role of GP IIb/IIIa inhibitors in STEMI in the context of more potent antiplatelet agents that may become available.


'''Associate Editor-In-Chief:'''  {{CZ}}
==Mechanism of Benefit of Glycoprotein IIb/IIIa Inhibition==


{{Editor Join}}
Glycoprotein IIb/IIIa inhibition blocks the cross-linking of [[fibrin]] strands to the platelet at the [[glycoprotein IIb/IIIa receptor]].  GPIIb/IIIa inhibition blocks the formation of new thrombus in this fashion, but high levels of inhibition have been associated with disaggregation of pre-existing clot <ref name="pmid12083481">{{cite journal |author=Marciniak SJ, Mascelli MA, Furman MI, Michelson AD, Jakubowski JA, Jordan RE, Marchese PJ, Frelinger AL |title=An additional mechanism of action of abciximab: dispersal of newly formed platelet aggregates |journal=[[Thrombosis and Haemostasis]] |volume=87 |issue=6 |pages=1020–5 |year=2002 |month=June |pmid=12083481 |doi= |url= |issn= |accessdate=2010-06-30}}</ref><ref name="pmid19548907">{{cite journal |author=Speich HE, Earhart AD, Hill SN, Cholera S, Kueter TJ, Smith JN, White MM, Jennings LK |title=Variability of platelet aggregate dispersal with glycoprotein IIb-IIIa antagonists eptifibatide and abciximab |journal=[[Journal of Thrombosis and Haemostasis : JTH]] |volume=7 |issue=6 |pages=983–91 |year=2009 |month=June |pmid=19548907 |doi=10.1111/j.1538-7836.2009.03432.x |url=http://dx.doi.org/10.1111/j.1538-7836.2009.03432.x |issn= |accessdate=2010-06-30}}</ref><ref name="pmid12658060">{{cite journal |author=Moser M, Bertram U, Peter K, Bode C, Ruef J |title=Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates |journal=[[Journal of Cardiovascular Pharmacology]] |volume=41 |issue=4 |pages=586–92 |year=2003 |month=April |pmid=12658060 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0160-2446&volume=41&issue=4&spage=586 |issn= |accessdate=2010-06-30}}</ref><ref name="pmid17599433">{{cite journal |author=Gibson CM, Buros J, Ciaglo LN, Southard MC, Takao S, Harrigan C, Filopei J, Lew M, Marble SJ, Murphy SA, Cohen MG |title=Impact of iodinated contrast injections on percent diameter coronary arterial stenosis and implications for trials of intracoronary pharmacotherapies in patients with ST-elevation myocardial infarction |journal=[[The American Journal of Cardiology]] |volume=100 |issue=1 |pages=13–7 |year=2007 |month=July |pmid=17599433 |doi=10.1016/j.amjcard.2007.01.068 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(07)00563-2 |issn= |accessdate=2010-06-30}}</ref>.


==Mechanism of Benefit==
Among STEMI patients, Gibson et al have demonstrated that a greater number of glycoprotein IIb/IIIa receptors occupied is associated with improved [[myocardial perfusion]], ST segment resolution and [[coronary blood flow]] <ref name="pmid15262838">{{cite journal |author=Gibson CM, Jennings LK, Murphy SA, Lorenz DP, Giugliano RP, Harrington RA, Cholera S, Krishnan R, Califf RM, Braunwald E |title=Association between platelet receptor occupancy after eptifibatide (integrilin) therapy and patency, myocardial perfusion, and ST-segment resolution among patients with ST-segment-elevation myocardial infarction: an INTEGRITI (Integrilin and Tenecteplase in Acute Myocardial Infarction) substudy |journal=[[Circulation]] |volume=110 |issue=6 |pages=679–84 |year=2004 |month=August |pmid=15262838 |doi=10.1161/01.CIR.0000137912.11655.F6 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15262838 |issn= |accessdate=2010-06-30}}</ref><ref name="pmid20124127">{{cite journal |author=Deibele AJ, Jennings LK, Tcheng JE, Neva C, Earhart AD, Gibson CM |title=Intracoronary eptifibatide bolus administration during percutaneous coronary revascularization for acute coronary syndromes with evaluation of platelet glycoprotein IIb/IIIa receptor occupancy and platelet function: the Intracoronary Eptifibatide (ICE) Trial |journal=[[Circulation]] |volume=121 |issue=6 |pages=784–91 |year=2010 |month=February |pmid=20124127 |doi=10.1161/CIRCULATIONAHA.109.882746 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=20124127 |issn= |accessdate=2010-06-30}}</ref>.


Administration of glycoprotein IIb/IIIa inhibitors alone for reperfusion therapy (i.e., without combining a fibrinolytic or in conjunction with PCI) is not suggested. The isolated use of a GP IIb/IIIa inhibitor does not restore TIMI 3 flow in a sufficient proportion of patients to make it a viable pharmacologic strategy.<ref name="pmid10599535">{{cite journal |author=Holper EM, Giugliano RP, Antman EM |title=Glycoprotein IIb/IIIa inhibitors in acute ST segment elevation myocardial infarction |journal=Coron. Artery Dis. |volume=10 |issue=8 |pages=567–73 |year=1999 |month=December |pmid=10599535 |doi= |url=}}</ref> To improve rates of achieving TIMI 3 flow by applied pharmacological reperfusion therapy, GP IIb/IIIa antagonists have been combined with fibrinolytic agents to achieve both platelet disaggregation and fibrinolysis.<ref name="pmid10637197">{{cite journal |author=Gibson CM, Cannon CP, Murphy SA, ''et al'' |title=Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs |journal=Circulation |volume=101 |issue=2 |pages=125–30 |year=2000 |month=January |pmid=10637197 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10637197}}</ref><ref name="pmid10859283">{{cite journal |author= |title=Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group |journal=Circulation |volume=101 |issue=24 |pages=2788–94 |year=2000 |month=June |pmid=10859283 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10859283}}</ref>
Among patients with ST elevation myocardial infarction, treatment with GPIIb/IIIa inhibitors has been associated with improved epicardial patency ([[TIMI 3 flow]] improves from approximately 15% to 30%) and improved [[myocardial perfusion]] on arrival to the cardiac catheterization laboratory <ref name="pmid16996831">{{cite journal |author=Gibson CM, Kirtane AJ, Murphy SA, Rohrbeck S, Menon V, Lins J, Kazziha S, Rokos I, Shammas NW, Palabrica TM, Fish P, McCabe CH, Braunwald E |title=Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial |journal=[[American Heart Journal]] |volume=152 |issue=4 |pages=668–75 |year=2006 |month=October |pmid=16996831 |doi=10.1016/j.ahj.2006.06.003 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-8703(06)00521-7 |issn= |accessdate=2010-06-30}}</ref>. Despite these improved rates of flow and perfusion, the isolated use of a GP IIb/IIIa inhibitor does not restore TIMI 3 flow in a sufficient proportion of patients to make it a viable stand alone pharmacologic strategy in the absence of adjunctive PCI.  To improve the rate of normal TIMI grade 3 flow on arrival to the cardiac catheterization laboratory, GP IIb/IIIa antagonists have been combined with fibrinolytic agents.<ref name="pmid10351964">{{cite journal |author=Antman EM, Giugliano RP, Gibson CM, McCabe CH, Coussement P, Kleiman NS, Vahanian A, Adgey AA, Menown I, Rupprecht HJ, Van der Wieken R, Ducas J, Scherer J, Anderson K, Van de Werf F, Braunwald E |title=Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators |journal=[[Circulation]] |volume=99 |issue=21 |pages=2720–32 |year=1999 |month=June |pmid=10351964 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10351964 |issn= |accessdate=2010-06-30}}</ref><ref name="pmid10859283">{{cite journal |author= |title=Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group |journal=Circulation |volume=101 |issue=24 |pages=2788–94 |year=2000 |month=June |pmid=10859283 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10859283}}</ref> Despite the improvement in epicardial vessel patency with the combination of these agents, clinical outcomes were not meaningfully improved <ref name="pmid11425410">{{cite journal |author=Topol EJ |title=Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial |journal=[[Lancet]] |volume=357 |issue=9272 |pages=1905–14 |year=2001 |month=June |pmid=11425410 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673600050595 |issn= |accessdate=2010-06-30}}</ref> <ref name="pmid12413372">{{cite journal |author=Lincoff AM, Califf RM, Van de Werf F, Willerson JT, White HD, Armstrong PW, Guetta V, Gibler WB, Hochman JS, Bode C, Vahanian A, Steg PG, Ardissino D, Savonitto S, Bar F, Sadowski Z, Betriu A, Booth JE, Wolski K, Waller M, Topol EJ |title=Mortality at 1 year with combination platelet glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction: GUSTO V randomized trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=288 |issue=17 |pages=2130–5 |year=2002 |month=November |pmid=12413372 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=12413372 |issn= |accessdate=2010-06-30}}</ref>, and the combination of these agents prior to cardiac catheterization for STEMI has largely fallen out of favor.


==Clinical Trial Data==
==Clinical Trial Data==
===Facilitated PCI Using a Glycoprotein IIb/IIIa Inhibitor Alone in the Absence of Fibrinolytic Administration===
The [[glycoprotein IIb/IIIa inhibitors]] such as the small molecules [[tirofiban]], and [[eptifibatide]] as well as the large molecule [[abciximab]] have been associated with improved outcomes in primary PCI trials <ref name="pmid15827315">{{cite journal |author=De Luca G, Suryapranata H, Stone GW, ''et al'' |title=Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials |journal=JAMA |volume=293 |issue=14 |pages=1759–65 |year=2005 |month=April |pmid=15827315 |doi=10.1001/jama.293.14.1759 |url=}}</ref>  <ref name="pmid15265852">{{cite journal |author=Montalescot G, Borentain M, Payot L, Collet JP, Thomas D |title=Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis |journal=JAMA |volume=292 |issue=3 |pages=362–6 |year=2004 |month=July |pmid=15265852 |doi=10.1001/jama.292.3.362 |url=}}</ref>. One issue is the optimal timing of the administration of these agents: should they be administered in the emergency room prior to cardiac catheterization (which may cause a delay in transferring the patient to the cardiac catheterization laboratory), or should they be administered in the cardiac catheterization laboratory which may miss the potential benefit of opening the vessel prior to arrival in the cardiac catheterization laboratory.
====Comparisons of Glycoprotein IIb/IIIa Inhibitors====
There are few randomized trials directly comparing agents in this class. The Multicentre Evaluation of Single High-Dose Bolus [[Tirofiban]] vs. [[Abciximab]] With [[Sirolimus]]-Eluting Stent or Bare Metal Stent/ in Acute Myocardial Infarction (MULTISTRATEGY) trial compared the small molecule tirofiban with the large molecule abciximab in the management of [[primary PCI]] patients <ref name="pmid18375998">{{cite journal |author=Valgimigli M, Campo G, Percoco G, Bolognese L, Vassanelli C, Colangelo S, de Cesare N, Rodriguez AE, Ferrario M, Moreno R, Piva T, Sheiban I, Pasquetto G, Prati F, Nazzaro MS, Parrinello G, Ferrari R |title=Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=299 |issue=15 |pages=1788–99 |year=2008 |month=April |pmid=18375998 |doi=10.1001/jama.299.15.joc80026 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18375998 |issn= |accessdate=2010-06-30}}</ref>. While this was a randomized trial, it was not blinded. All 745 patients were treated with 300 mg of clopidogrel prior to cardiac catheterization.  There was a 2 X 2 randomization in the trial. The first level of randomization was to high dose [[tirofiban]] (25 μg/kg bolus regimen) versus abciximab, both administered at the time of first medical contact with the patient. The second level of randomization was to either [[sirolimus]]-eluting (SES) or bare metal stenting (BMS).  Given that only 745 patients were enrolled, a highly powered endpoint was chosen, which was ST segment resolution at 90 minutes following PCI.  ST segment resolution associated with tirofiban (85.3%) was statistically non-inferior to [[abciximab]] (83.6%)(RR, 1.020; 97.5% CI, 0.958-1.086; p<0 .001 for noninferiority). Consistent with these EKG findings of non-inferiority, there was likewise no difference in major adverse cardiac events (MACE) for tirofiban vs abciximab at either 30 days (4.0% vs. 4.3%, respectively; p=0.85)or 8 months (9.9% vs. 12.4% respectively; p=0.30. With respect to safety, there was a significant increase in the risk of [[thrombocytopenia]] associated with abciximab (0.5% for tirofiban versus 2.4% for abciximab: 2.4%; p=0.03). The increased risk of thrombocytopenia associated with abciximab has been consistently observed across multiple trials<ref name="pmid10925331">{{cite journal |author=Dasgupta H, Blankenship JC, Wood GC, Frey CM, Demko SL, Menapace FJ |title=Thrombocytopenia complicating treatment with intravenous glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis |journal=[[American Heart Journal]] |volume=140 |issue=2 |pages=206–11 |year=2000 |month=August |pmid=10925331 |doi=10.1067/mhj.2000.107554 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-8703(00)23552-7 |issn= |accessdate=2010-06-30}}</ref>.
In a smaller earlier trial called STRATEGY (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction), the same investigators compared the outcomes among STEMI patients treated with high-dose tirofiban plus a sirolimus-eluting stent (n = 87) versus abciximab plus a [[bare metal stent]] (n = 88) <ref name="pmid15870414">{{cite journal |author=Valgimigli M, Percoco G, Malagutti P, Campo G, Ferrari F, Barbieri D, Cicchitelli G, McFadden EP, Merlini F, Ansani L, Guardigli G, Bettini A, Parrinello G, Boersma E, Ferrari R |title=Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=293 |issue=17 |pages=2109–17 |year=2005 |month=May |pmid=15870414 |doi=10.1001/jama.293.17.2109 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15870414 |issn= |accessdate=2010-06-30}}</ref>. The hypothesis was that administration of tirofiban instead of abciximab would allow the expanded use of [[drug eluting stent]]s by nullifying the cost differential between sirolimus-eluting vs bare-metal stents.  The primary endpoint of death, nonfatal myocardial infarction, stroke, or binary restenosis at 8 months occurred in 19% of tirofiban patients versus 50% of abciximab patients (p<0.001).
A meta-analysis that incorporated randomized trial data from 6 trials involving 2,197 patients through Cotober 2008 indicates that there is no difference in outcomes between primary PCI patients treated with abciximab versus either high dose tirofiban (5 trials) versus eptifibatide (1 trial) <ref name="pmid19406342">{{cite journal |author=De Luca G, Ucci G, Cassetti E, Marino P |title=Benefits from small molecule administration as compared with abciximab among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-analysis |journal=[[Journal of the American College of Cardiology]] |volume=53 |issue=18 |pages=1668–73 |year=2009 |month=May |pmid=19406342 |doi=10.1016/j.jacc.2009.01.053 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(09)00542-7 |issn= |accessdate=2010-06-30}}</ref> Abciximab was not associated with an improvement in either the rate of TIMI flow grade 3 post PCI (89.8% vs. 89.1%, p = 0.72) or ST-segment resolution following PCI (67.8% vs. 68.2%, p = 0.66).  Likewise, abciximab was not associated with a reduction in either 30-day mortality (2.2% vs. 2.0%, p = 0.66) or reinfarction (1.2% vs. 1.2%, p = 0.88). No difference in [[bleeding]] was observed.
====Facilitated PCI Trials using Tirofiban====
Early upstream administration of [[tirofiban]] has been associated with better pre-PCI angiographic outcomes, but these studies were not sufficiently powered to demonstrate significant clinical benefit. The benefit of early administration of tirofiban compared to upstream administration was assessed in the TIGER-PA trial (TIrofiban Given in the Emergency Room before Primary Angioplasty). This study consisted of 100 patients who received tirofiban either in the ER or in the cath lab. There was a significant improvement in the initial angiographic parameters such as [[TIMI flow grade]] ([[TFG]]), [[corrected TIMI frame count]] (CTFC) and [[TIMI myocardial perfusion grade]] ([[TMPG]]). This study was not powered to demonstrate a significant clinical benefit <ref name="pmid12654606">{{cite journal |author=Lee DP, Herity NA, Hiatt BL, ''et al'' |title=Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial |journal=Circulation |volume=107 |issue=11 |pages=1497–501 |year=2003 |month=March |pmid=12654606 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12654606}}</ref>.
Likewise, the investigators from the On-TIME trial (Ongoing Tirofiban in myocardial infarction Evaluation) evaluated a similar strategy of administration of tirofiban approximately one hour before PCI compared to administration of tirofiban in the cath lab <ref name="pmid15140531">{{cite journal |author=van 't Hof AW, Ernst N, de Boer MJ, ''et al'' |title=Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial |journal=Eur. Heart J. |volume=25 |issue=10 |pages=837–46 |year=2004 |month=May |pmid=15140531 |doi=10.1016/j.ehj.2004.04.003 |url=}}</ref>.  The primary endpoint of TIMI grade 3 flow pre-PCI was not increased with the use of early tirofiban (19% vs. 15%, p=0.22), but TIMI grade 2 and 3 flow combined, thrombus burden and myocardial perfusion were improved.  This study also was not powered to demonstrate a clinical benefit.
In contrast to the above two studies, another small trial (RAPIER) demonstrated that the upstream use of tirofiban in the ER was not associated with a significant improvement in the rate of TIMI grade 2 or 3 flow compared with the delayed administration of tirofiban in the cardiac catheterization laboratory (39% vs. 27% p >0.2). There was, however, a trend towards improved ST segment resolution in the ER group (69% vs.77%, p=0.07) <ref name="pmid14556878">{{cite journal |author=Cutlip DE, Ricciardi MJ, Ling FS, ''et al'' |title=Effect of tirofiban before primary angioplasty on initial coronary flow and early ST-segment resolution in patients with acute myocardial infarction |journal=Am. J. Cardiol. |volume=92 |issue=8 |pages=977–80 |year=2003 |month=October |pmid=14556878 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914903009834}}</ref>.
====Facilitated PCI Trials using Abciximab====
The use of [[abciximab]] in the emergency room (ER) has likewise been compared to delayed administration in the cardiac catheterization laboratory. The RELax-AMI study (Randomized Early versus Late abciximab in Acute Myocardial Infarction treated with primary coronary intervention) included 210 patients with acute ST segment elevation myocardial infarction. Of these 105 patients received abciximab in the ER and the remaining 105 received abciximab in the cardiac catheterization laboratory.  This study demonstrated significant improvements in the pre-PCI angiographic parameters including TIMI grade 3 flow (24% vs. 10%, p=0.01), corrected [[TIMI frame count]] (78±30 vs. 92±21, p=0.001) and myocardial blush grade (MBG 2/3) [15% vs. 6%, p=0.02] in the early abciximab group compared to the upstream group. The post-PCI ST segment resolution (>70%) was greater in the early abciximab group (50% vs. 35%, p=0.03) and the myocardial blush grade following PCI was also improved (MBG 2/3 79% vs. 58%, p=0.001). The one month ejection fraction was significantly better in the early group <ref name="pmid17418289">{{cite journal |author=Maioli M, Bellandi F, Leoncini M, Toso A, Dabizzi RP |title=Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial) |journal=J. Am. Coll. Cardiol. |volume=49 |issue=14 |pages=1517–24 |year=2007 |month=April |pmid=17418289 |doi=10.1016/j.jacc.2006.12.036 |url=}}</ref>. 
Similarly, the ERAMI trial (Early Reopro Administration in Myocardial Infarction) demonstrated significant improvements in the post PCI CTFC and increased rate of normal [[TIMI Myocardial Perfusion Grade]] 3 among patients who received abciximab in the ER compared to those who received it in the cath lab despite an absence of any difference in pre-PCI angiographic parameters <ref name="pmid16817177">{{cite journal |author=Gabriel HM, Oliveira JA, da Silva PC, da Costa JM, da Cunha JA |title=Early administration of abciximab bolus in the emergency department improves angiographic outcome after primary PCI as assessed by TIMI frame count: results of the early ReoPro administration in myocardial infarction (ERAMI) trial |journal=Catheter Cardiovasc Interv |volume=68 |issue=2 |pages=218–24 |year=2006 |month=August |pmid=16817177 |doi=10.1002/ccd.20798 |url=}}</ref>.
Multiple other studies have demonstrated similar improvements in angiographic outcomes associated with early administration. Zorman et al demonstrated that ER administration of abciximab resulted in increased patency rates, improved ST segment resolution, and better survival compared to administration of abciximab in the cath lab <ref name="pmid12208418">{{cite journal |author=Zorman S, Zorman D, Noc M |title=Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplasty |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=533–6 |year=2002 |month=September |pmid=12208418 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914902025304}}</ref>. Bellandi et al demonstrated not only an increase in the rate of TIMI grade 3 flow and improved [[TIMI Frame Count]] / myocardial blush grade but also left ventricular function recovery compared to delayed abciximab administration in the cardiac catheterization laboratory <ref name="pmid15927285">{{cite journal |author=Bellandi F, Maioli M, Leoncini M, Toso A, Dabizzi RP |title=Early abciximab administration in acute myocardial infarction treated with primary coronary intervention |journal=Int. J. Cardiol. |volume=108 |issue=1 |pages=36–42 |year=2006 |month=March |pmid=15927285 |doi=10.1016/j.ijcard.2005.04.025 |url=}}</ref>.  Finally, the ReoPro- BRIDGING study also demonstrated that early administration of abciximab was associated with increased patency of infarct arteries and improved myocardial perfusion <ref name="pmid15571828">{{cite journal |author=Gyöngyösi M, Domanovits H, Benzer W, ''et al'' |title=Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion - results of the Austrian multi-centre randomized ReoPro-BRIDGING Study |journal=Eur. Heart J. |volume=25 |issue=23 |pages=2125–33 |year=2004 |month=December |pmid=15571828 |doi=10.1016/j.ehj.2004.09.018 |url=}}</ref>.
====Facilitated PCI Trials using Eptifibatide====
Comparable to studies using tirofiban and abciximab, in the INTAMI study (INTegrilin in Acute Myocardial Infarction), Zeymer et al demonstrated that administration of [[eptifibatide]] in the ER was associated increased TFG 3 pre PCI compared to administration in the cath lab (34% vs. 10%, p=0.01) <ref name="pmid15857851">{{cite journal |author=Zeymer U, Zahn R, Schiele R, ''et al'' |title=Early eptifibatide improves TIMI 3 patency before primary percutaneous coronary intervention for acute ST elevation myocardial infarction: results of the randomized integrilin in acute myocardial infarction (INTAMI) pilot trial |journal=Eur. Heart J. |volume=26 |issue=19 |pages=1971–7 |year=2005 |month=October |pmid=15857851 |doi=10.1093/eurheartj/ehi293 |url=}}</ref>. But there was no difference in the [[TFG]] 3 post-PCI, death, [[reinfarction]], [[stroke]] and major bleed up to 30 days.


==Dosing==
The TITAN TIMI-34 (Time to Integrilin Therapy in Acute Myocardial Infarction) was a larger trial than the INTAMI trial consisting of a total of 343 STEMI patients of which 180 received eptifibatide in the ER compared to 163 who received the drug in the cath lab. The primary endpoint, pre [[PCI]] corrected [[TIMI frame count]] was significantly better in the ER group compared to the cath lab group (77.5±32.2 vs. 84.3±30.7, p=0.049). The pre PCI TMPG 3 was more frequently seen in the ER group (24% vs. 14%, p=0.026). However there was no difference in the [[bleeding]] events and clinical outcomes between the two groups <ref name="pmid16996831">{{cite journal |author=Gibson CM, Kirtane AJ, Murphy SA, ''et al'' |title=Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial |journal=Am. Heart J. |volume=152 |issue=4 |pages=668–75 |year=2006 |month=October |pmid=16996831 |doi=10.1016/j.ahj.2006.06.003 |url=}}</ref>.


==Side Effects==
====Facilitated PCI Trials Combining Low Dose Fibrinolytic Agent and Glycoprotein IIb/IIIa Inhibitor====
Given the discrepancies in the outcomes in [[facilitated PCI]] using fibrinolytic alone and glycoprotein IIb/IIIa inhibitor alone, a strategy of combined therapy using low dose fibrinolytic and full dose glycoprotein IIb/IIIa inhibitor was examined. The Strategies for Patency Enhancement in the Emergency Department (SPEED-GUSTO-4 Pilot trial) examined the benefit of administration of fibrinolytic with or without [[abciximab]] among patients undergoing early PCI following an acute MI. This non randomized study demonstrated that administration of a half-dose [[reteplase]] and abciximab was safe and effective. This strategy was associated with [[TIMI flow grade]] 3 in 86% of cases at 90 minutes and the composite end point of death, [[reinfarction]] and urgent revascularization occurred in 5.6% of cases in the PCI group compared to 16% in those who did not undergo PCI<ref name="pmid11079647">{{cite journal |author=Herrmann HC, Moliterno DJ, Ohman EM, ''et al'' |title=Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial |journal=J. Am. Coll. Cardiol. |volume=36 |issue=5 |pages=1489–96 |year=2000 |month=November |pmid=11079647 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(00)00923-2}}</ref>.


==ACC / AHA Guidelines- Glycoprotein IIb/IIIa Inhibitors (DO NOT EDIT)<ref name="pmid15289388">{{cite journal |author=Antman EM, Anbe DT, Armstrong PW, ''et al'' |title=ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction) |journal=Circulation |volume=110 |issue=5 |pages=588–636 |year=2004 |month=August |pmid=15289388 |doi=10.1161/01.CIR.0000134791.68010.FA |url=}}</ref><ref name="2009 STEMI guidelines">{{[http://content.onlinejacc.org/cgi/content/full/j.jacc.2009.10.015]}}</ref>==
The Alteplase and [[Tirofiban]] in Acute Myocardial Infarction (ATAMI), a small single center study demonstrated that there was significantly high rates of TIMI grade 2/3 flow among STEMI patients randomized to combination therapy with 50mg [[alteplase]] and tirofiban prior to planned [[PCI]] compared to upstream administration of tirofiban in the catheter laboratory (87% vs. 42%, p<0.0001). These groups were compared with a matched control patients who underwent PCI with provisional abciximab in the cath lab (29% of patients had TIMI flow grade 2/3). The 30-day mortality was significantly lower in the combination therapy group compared to upstream tirofiban group and the control group (0.7% vs. 5.5%, p<0.02 vs. 6.3%). There were no differences in the incidence of bleeding events between the three groups<ref name="pmid18055037">{{cite journal |author=Peters S, Truemmel M, Koehler B |title=Facilitated PCI by combination fibrinolysis or upstream tirofiban in acute ST-segment elevation myocardial infarction: results of the Alteplase and Tirofiban in Acute Myocardial Infarction (ATAMI) trial |journal=Int. J. Cardiol. |volume=130 |issue=2 |pages=235–40 |year=2008 |month=November |pmid=18055037 |doi=10.1016/j.ijcard.2007.08.048 |url=}}</ref>. This study has its limitations given the fact that this was a single center study with relatively small number of patients and a lower dose of tirofiban was used (10μg/kg).


===Class IIa===
Contrary to the SPEED and the ATAMI studies, the BRAVE (Bavarian Reperfusion Alternatives Evaluation) study by Kastrati and coworkers was an open label, randomized multi-center study in which the beneficial effect of the use of half dose [[reteplase]] and [[abciximab]] on the infarct size using [[single photon emission tomography]] ([[SPECT]]) was examined. The investigators did not demonstrate any improvement in the final infarct size using the combination therapy (n=125) compared to abciximab alone (n=128) among STEMI patients referred for PCI (mean difference in the infarct size was 1.3% between the two groups). There was no difference in the secondary endpoints such as death, reinfarction or [[stroke]] <ref name="pmid14982910">{{cite journal |author=Kastrati A, Mehilli J, Schlotterbeck K, ''et al'' |title=Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial |journal=JAMA |volume=291 |issue=8 |pages=947–54 |year=2004 |month=February |pmid=14982910 |doi=10.1001/jama.291.8.947 |url=}}</ref>. A similar strategy was examined in APAMIT (Asia Pacific Myocardial Infarction Trial) where all STEMI patients received abciximab and were randomized to either immediate PCI or to PCI sixty minutes later following the administration of alteplase. Like all previous studies this study demonstrated that facilitation with a lytic in addition to abciximab was associated with an increase TFG 3 pre PCI but no difference in the clinical outcomes<ref name="pmid15274152">{{cite journal |author=Wong A, Mak KH, Chan C, ''et al'' |title=Combined fibrinolysis using reduced-dose alteplase plus abciximab with immediate rescue angioplasty versus primary angioplasty with adjunct use of abciximab for the treatment of acute myocardial infarction: Asia-Pacific Acute Myocardial Infarction Trial (APAMIT) pilot study |journal=Catheter Cardiovasc Interv |volume=62 |issue=4 |pages=445–52 |year=2004 |month=August |pmid=15274152 |doi=10.1002/ccd.20101 |url=}}</ref>.           


1. It is reasonable to start treatment with glycoprotein IIb/IIIa receptor antagonists (abciximab [''Level of Evidence: A''], tirofiban [''Level of Evidence: B''] or eptifibatide [''Level of Evidence: B'']) at the time of primary PCI (with or without stenting) in selected patients with STEMI.
Given the small sample size in the above studies, another randomized study, the ADVANCE-MI (ADressing the Value of facilitated Angioplasty after Combination therapy or Eptifibatide monotherapy in acute Myocardial Infarction) study was designed to answer similar questions whether a strategy of combination fibrinolytic and a different glycoprotein IIb/IIIa inhibitor ([[eptifibatide]]) compared to eptifibatide + placebo prior to PCI would improve clinical outcomes. Although this study originally planned to recruit 5640 patients, it was prematurely terminated because of slow recruitment. An analysis of a total of 148 patients suggested that combination therapy (reduced dose [[tenecteplase]] and eptifibatide) was associated with improved epicardial flow and myocardial tissue perfusion on pre-PCI angiography. This strategy however resulted in a trend towards an increase in adverse outcomes (death, new/worsening heart failure or bleeding) compared to eptifibatide + placebo group<ref name="pmid16084157">{{cite journal |author= |title=Facilitated percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: results from the prematurely terminated ADdressing the Value of facilitated ANgioplasty after Combination therapy or Eptifibatide monotherapy in acute Myocardial Infarction (ADVANCE MI) trial |journal=Am. Heart J. |volume=150 |issue=1 |pages=116–22 |year=2005 |month=July |pmid=16084157 |doi=10.1016/j.ahj.2005.04.005 |url=}}</ref>.


===Class IIb===
The FINESSE trial (the largest trial on combination therapy) results were presented in the European Society of Cardiology meetings in 2007 (www.escardio.org). The Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) study is a 3000-patient, prospective, multicenter, randomized, double-blind, placebo-controlled trial. The study was designed to compare the efficacy and safety of early administration of reduced-dose reteplase and abciximab combination therapy or abciximab alone followed by PCI with abciximab alone administered just before PCI for acute STEMI. Patients were randomized to one of the two facilitated PCI treatments or primary PCI in a 1:1:1 fashion<ref name="pmid15077099">{{cite journal |author=Ellis SG, Armstrong P, Betriu A, ''et al'' |title=Facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention: design and rationale of the Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) trial |journal=Am. Heart J. |volume=147 |issue=4 |pages=E16 |year=2004 |month=April |pmid=15077099 |doi=10.1016/j.ahj.2003.07.025 |url=}}</ref>. At 90 days, there were no differences between treatment arms for the primary composite end points of the trial: all-cause mortality, readmission for heart failure, ventricular fibrillation, or cardiogenic shock [10.7% (PCI only group, n=806) vs. 10.5% (abciximab facilitated group, n=818) vs. 9.8% (reteplase and abciximab group, n=828)]. There were also no differences in all-cause mortality (4.5% vs. 5.5% vs. 5.2% respectively), complications of MI (8.9% vs. 7.5% vs. 7.4%), or any of the independent components of the primary composite end point. For safety end points, rates of TIMI major bleeding and minor bleeding were significantly higher for the abciximab/lytic facilitated PCI strategy as compared with primary PCI (14.5% vs. 6.9%, p<0.001). There was also a strong trend towards increased [[intracranial hemorrhage]] through discharge or day seven in the combined abciximab/lytic facilitation approach.


1. The usefulness of glycoprotein IIb/IIIa receptor antagonists (as part of a preparatory pharmacological strategy for patients with STEMI before their arrival in the cardiac catheterization laboratory for angiography and PCI) is uncertain. ''(Level of Evidence: B)''
More recently, although not truly a facilitated PCI study, the CARESS-in-AMI (Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction) study determined whether early transfer for PCI following pharmacotherapy administration improves outcomes compared to a conservative watchful waiting approach among patients with STEMI with anticipated delay in primary PCI due to their presentation to a non-PCI center<ref name="pmid18280326">{{cite journal |author=Di Mario C, Dudek D, Piscione F, ''et al'' |title=Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial |journal=Lancet |volume=371 |issue=9612 |pages=559–68 |year=2008 |month=February |pmid=18280326 |doi=10.1016/S0140-6736(08)60268-8 |url=}}</ref>. Six hundred patients in this study were pretreated with aspirin, heparin, half dose reteplase and abciximab. Subsequently patients were randomized to either immediate transfer for PCI or transfer only in case of failed reperfusion or clinical deterioration. The investigators demonstrated that there was significant benefit in terms of reduction in 30-day mortality with the immediate transfer strategy (4.4% vs. 10.7%, p=0.004) without any differences in the bleeding events. It is important to note that the CARESS-in-AMI study determines whether early PCI improves pharmacotherapy outcomes. This is in contrast to the facilitated PCI strategy where pharmacotherapy is administered to improve PCI outcomes.


==ACC / AHA Guidelines- Combination Therapy With Glycoprotein IIb/IIIa Inhibitors (DO NOT EDIT)<ref name="pmid15289388">{{cite journal |author=Antman EM, Anbe DT, Armstrong PW, ''et al'' |title=ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction) |journal=Circulation |volume=110 |issue=5 |pages=588–636 |year=2004 |month=August |pmid=15289388 |doi=10.1161/01.CIR.0000134791.68010.FA |url=}}</ref><ref name="2009 STEMI guidelines"/>==
==Use of Glycoprotein IIb/IIIa Inhibitors in Rescue PCI Following Failed Fibrinolysis==
In contrast to [[primary PCI]], there is no clinical benefit of GPIIb/IIIa inhibition when added to the administration of a full dose of a [[fibrinolytic]] agent when co-administered at the time of presentation with STEMI.  This combination is clearly associated with increased [[bleeding]], particularly in the elderly <ref name="pmid11425410">{{cite journal |author=Topol EJ |title=Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial |journal=[[Lancet]] |volume=357 |issue=9272 |pages=1905–14 |year=2001 |month=June |pmid=11425410 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673600050595 |issn= |accessdate=2010-06-30}}</ref>.  The benefit of glycoprotein IIb/IIIa administration in the cardiac catheterization laboratory several hours after fibrinloytic administration is supported by non-randomized observational data <ref> Roe MT, Giugliano RP, Tuttle R, Hasselbad V, Murphy SA, Antman EM, Ohman EM, Harrington RA, Granger CB, Mahaffey KW, Cannon CP, Lincoff AM, Gibson CM, Armstrong PW, van de Werf FJ, Califf RM, Topol EJ, Braunwald E. Safety of Adjunctive Glycoprotein IIb/IIIa Blockade During Rescue/Early Percutaneous Coronary Intervention Following Full-Dose Fibrinolytic Therapy for Acute Myocardial Infarction. J Am Coll Cardiol 2003;41(6 Suppl A):332A.</ref><ref name="pmid16446517">{{cite journal |author=Gruberg L, Suleiman M, Kapeliovich M, Hammerman H, Grenadier E, Boulus M, Amikam S, Markiewicz W, Beyar R |title=Glycoprotein IIb/IIIa inhibitors during rescue percutaneous coronary intervention in acute myocardial infarction |journal=[[The Journal of Invasive Cardiology]] |volume=18 |issue=2 |pages=59–62 |year=2006 |month=February |pmid=16446517 |doi= |url= |issn= |accessdate=2010-06-30}}</ref>.  In a small non-randomized study of 59 consecutive patients at a single institution, [[death]], [[reinfarction]] and urgent target vessel revascularization was significantly lower among patients treated with GP IIb/IIIa inhibition as compared with patients who were not treated (3.4% vs. 26.7%; p = 0.01).


===Class IIb===
==Side Effects and Complications of GP IIb/IIIa Inhibitors==
===Thrombocytopenia===
[[Abciximab]] has consistently been associated with the development of [[thrombocytopenia]] <ref name="pmid10925331">{{cite journal |author=Dasgupta H, Blankenship JC, Wood GC, Frey CM, Demko SL, Menapace FJ |title=Thrombocytopenia complicating treatment with intravenous glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis |journal=[[American Heart Journal]] |volume=140 |issue=2 |pages=206–11 |year=2000 |month=August |pmid=10925331 |doi=10.1067/mhj.2000.107554 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-8703(00)23552-7 |issn= |accessdate=2010-06-30}}</ref>. In one meta-analysis, abciximab but not small molecule GP IIb/IIIa inhibitors was associated with an increased risk of mild thrombocytopenia when compared to placebo (4.2% vs 2.0%; P <.001; odds ratio 2.14) as well as severe thrombocytopenia as compared with placebo (1.0% vs 0.4%; P =.01; odds ratio 2.48).  Thrombocytipenia has been in turn associated with an increase risk of major [[bleeding]], [[transfusion]], [[recurrent MI]], [[stroke]] and both in-hosptial and 30 day [[mortality]] <ref name="pmid19121432">{{cite journal |author=Gore JM, Spencer FA, Gurfinkel EP, López-Sendón J, Steg PG, Granger CB, FitzGerald G, Agnelli G |title=Thrombocytopenia in patients with an acute coronary syndrome (from the Global Registry of Acute Coronary Events [GRACE]) |journal=[[The American Journal of Cardiology]] |volume=103 |issue=2 |pages=175–80 |year=2009 |month=January |pmid=19121432 |doi=10.1016/j.amjcard.2008.08.055 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(08)01515-4 |issn= |accessdate=2010-06-30}}</ref><ref name="pmid15117843">{{cite journal |author=Merlini PA, Rossi M, Menozzi A, Buratti S, Brennan DM, Moliterno DJ, Topol EJ, Ardissino D |title=Thrombocytopenia caused by abciximab or tirofiban and its association with clinical outcome in patients undergoing coronary stenting |journal=[[Circulation]] |volume=109 |issue=18 |pages=2203–6 |year=2004 |month=May |pmid=15117843 |doi=10.1161/01.CIR.0000127867.41621.85 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15117843 |issn= |accessdate=2010-06-30}}</ref><ref name="pmid16098296">{{cite journal |author=Nikolsky E, Sadeghi HM, Effron MB, Mehran R, Lansky AJ, Na Y, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Stuckey TD, Turco M, Carroll JD, Grines CL, Stone GW |title=Impact of in-hospital acquired thrombocytopenia in patients undergoing primary angioplasty for acute myocardial infarction |journal=[[The American Journal of Cardiology]] |volume=96 |issue=4 |pages=474–81 |year=2005 |month=August |pmid=16098296 |doi=10.1016/j.amjcard.2005.04.005 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(05)00838-6 |issn= |accessdate=2010-06-30}}</ref><ref name="pmid19398666">{{cite journal |author=Wang TY, Ou FS, Roe MT, Harrington RA, Ohman EM, Gibler WB, Peterson ED |title=Incidence and prognostic significance of thrombocytopenia developed during acute coronary syndrome in contemporary clinical practice |journal=[[Circulation]] |volume=119 |issue=18 |pages=2454–62 |year=2009 |month=May |pmid=19398666 |doi=10.1161/CIRCULATIONAHA.108.827162 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=19398666 |issn= |accessdate=2010-06-30}}</ref>


1. Combination pharmacological [[reperfusion]] with [[abciximab]] and half-dose [[reteplase]] or [[tenecteplase]] may be considered for prevention of reinfarction ''(Level of Evidence: A)'' and other complications of [[STEMI]] in selected patients: [[anterior]] location of [[MI]], age less than 75 years, and no risk factors for bleeding. In two clinical trials of combination [[reperfusion]], the prevention of reinfarction did not translate into a survival benefit at either 30 days or 1 year. ''(Level of Evidence: B)''
== 2013 Revised, 2009 and 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction and 2011 ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention,  (DO NOT EDIT)<ref name="pmid23247303">{{cite journal |author=O'Gara PT, Kushner FG, Ascheim DD, ''et al.'' |title=2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines |journal=Circulation |volume= |issue= |pages= |year=2012 |month=December |pmid=23247303 |doi=10.1161/CIR.0b013e3182742c84 |url=}}</ref><ref name="pmid22070837">{{cite journal |author=Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH |title=2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions |journal=[[Journal of the American College of Cardiology]] |volume=58 |issue=24 |pages=2550–83 |year=2011 |month=December|pmid=22070837|doi=10.1016/j.jacc.2011.08.006|url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(11)02875-0|accessdate=2011-12-08|url=http://content.onlinejacc.org/cgi/reprint/58/24/2550.pdf|PDF}}</ref><ref name="pmid19923169">{{cite journal| author=Kushner FG, Hand M, Smith SC, King SB, Anderson JL, Antman EM et al.| title=2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2009 | volume= 120 | issue= 22 | pages= 2271-306 | pmid=19923169 |doi=10.1161/CIRCULATIONAHA.109.192663 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19923169  }} </ref><ref name="pmid15289388">{{cite journal| author=Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M et al.| title=ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). | journal=Circulation |year= 2004 | volume= 110 | issue= 5 | pages= 588-636 | pmid=15289388 | doi=10.1161/01.CIR.0000134791.68010.FA | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15289388  }}</ref>==
===Intravenous Antiplatelet Therapy in Patients of ST-Elevation Myocardial Infarction (STEMI) (DO NOT EDIT)<ref name="pmid23247303">{{cite journal |author=O'Gara PT, Kushner FG, Ascheim DD, ''et al.'' |title=2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines |journal=Circulation |volume= |issue= |pages= |year=2012 |month=December |pmid=23247303 |doi=10.1161/CIR.0b013e3182742c84 |url=}}</ref><ref name="pmid22070837">{{cite journal |author=Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH|title=2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions|journal=[[Journal of the American College of Cardiology]] |volume=58 |issue=24 |pages=2550–83 |year=2011|month=December|pmid=22070837|doi=10.1016/j.jacc.2011.08.006|url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(11)02875-0|accessdate=2011-12-08|url=http://content.onlinejacc.org/cgi/reprint/58/24/2550.pdf|PDF}}</ref>===


2. Combination pharmacological [[reperfusion]] with [[abciximab]] and half-dose [[reteplase]] or [[tenecteplase]] may be considered for prevention of reinfarction and other complications of [[STEMI]] in selected patients: [[anterior]] location of [[MI]], age less than 75 years, and no risk factors for bleeding in whom an early referral for [[angiography]] and [[PCI]] (i.e., [[facilitated PCI]]) is planned. ''(Level of Evidence: C)''
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (No Benefit)
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' Routine pre-catheterization laboratory (e.g., ambulance or emergency room) administration of [[glycoprotein IIb/IIIa inhibitors]] as part of an upstream strategy for patients with [[STEMI]] undergoing [[ST elevation myocardial infarction primary percutaneous coronary intervention|PCI]] is not beneficial.<ref name="pmid15265852">{{cite journal |author=Montalescot G, Borentain M, Payot L, Collet JP, Thomas D|title=Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis|journal=[[JAMA : the Journal of the American Medical Association]] |volume=292 |issue=3|pages=362–6 |year=2004 |month=July |pmid=15265852 |doi=10.1001/jama.292.3.362|url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15265852|accessdate=2011-12-12}}</ref><ref name="pmid17418289">{{cite journal |author=Maioli M, Bellandi F, Leoncini M, Toso A, Dabizzi RP |title=Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial) |journal=[[Journal of the American College of Cardiology]] |volume=49 |issue=14 |pages=1517–24 |year=2007 |month=April|pmid=17418289 |doi=10.1016/j.jacc.2006.12.036|url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(07)00335-X|accessdate=2011-12-12}}</ref><ref name="pmid16488801">{{cite journal |author=Keeley EC, Boura JA, Grines CL |title=Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials |journal=[[Lancet]]|volume=367 |issue=9510 |pages=579–88 |year=2006 |month=February |pmid=16488801|doi=10.1016/S0140-6736(06)68148-8|url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(06)68148-8|accessdate=2011-12-12}}</ref><ref name="pmid18707985">{{cite journal |author=Van't Hof AW, Ten Berg J, Heestermans T, Dill T, Funck RC, van Werkum W, Dambrink JH, Suryapranata H, van Houwelingen G, Ottervanger JP, Stella P, Giannitsis E, Hamm C |title=Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial |journal=[[Lancet]] |volume=372 |issue=9638|pages=537–46 |year=2008 |month=August |pmid=18707985 |doi=10.1016/S0140-6736(08)61235-0|url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61235-0|accessdate=2011-12-12}}</ref><ref name="pmid20510211">{{cite journal |author=ten Berg JM, van 't Hof AW, Dill T, Heestermans T, van Werkum JW, Mosterd A, van Houwelingen G, Koopmans PC, Stella PR, Boersma E, Hamm C |title=Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome|journal=[[Journal of the American College of Cardiology]] |volume=55 |issue=22 |pages=2446–55|year=2010 |month=June |pmid=20510211 |doi=10.1016/j.jacc.2009.11.091|url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(10)01154-X|accessdate=2011-12-12}}</ref><ref name="pmid19850248">{{cite journal |author=Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Andersen HR, Betriu A, Savonitto S, Adamus J, Peruga JZ, Hamankiewicz M, Pluta W, Oldroyd K, Ecollan P, Janssens L, Armstrong P, Brodie BR, Herrmann HC, Montalescot G, Neumann FJ, Effron MB, Barnathan ES, Topol EJ |title=1-year survival in a randomized trial of facilitated reperfusion: results from the FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) trial |journal=[[JACC. Cardiovascular Interventions]] |volume=2|issue=10 |pages=909–16 |year=2009 |month=October |pmid=19850248 |doi=10.1016/j.jcin.2009.07.009|url=http://linkinghub.elsevier.com/retrieve/pii/S1936-8798(09)00513-5|accessdate=2011-12-12}}</ref><ref name="pmid18499565">{{cite journal |author=Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Janssens L, Andersen HR, Betriu A, Savonitto S, Adamus J, Peruga JZ, Kosmider M, Katz O, Neunteufl T, Jorgova J, Dorobantu M, Grinfeld L, Armstrong P, Brodie BR, Herrmann HC, Montalescot G, Neumann FJ, Effron MB, Barnathan ES, Topol EJ |title=Facilitated PCI in patients with ST-elevation myocardial infarction |journal=[[The New England Journal of Medicine]]|volume=358 |issue=21 |pages=2205–17 |year=2008 |month=May |pmid=18499565 |doi=10.1056/NEJMoa0706816|url=http://dx.doi.org/10.1056/NEJMoa0706816 |accessdate=2011-12-12}}</ref><ref name="pmid20619238">{{cite journal |author=El Khoury C, Dubien PY, Mercier C, Belle L, Debaty G, Capel O, Perret T, Savary D, Serre P, Bonnefoy E |title=Prehospital high-dose tirofiban in patients undergoing primary percutaneous intervention. The AGIR-2 study |journal=[[Archives of Cardiovascular Diseases]] |volume=103 |issue=5 |pages=285–92 |year=2010 |month=May |pmid=20619238|doi=10.1016/j.acvd.2010.04.005|url=http://linkinghub.elsevier.com/retrieve/pii/S1875-2136(10)00088-4|accessdate=2011-12-12}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


===Class III===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients undergoing [[ST elevation myocardial infarction primary percutaneous coronary intervention#Primary PCI|primary PCI]] treated with [[ST elevation myocardial infarction anticoagulant and antithrombotic therapy#Unfractionated Heparin|unfractionated heparin (UFH)]], it is reasonable to administer a [[glycoprotein IIb/IIIa inhibitor]] ([[abciximab]], [[eptifibatide|double-bolus eptifibatide]], or [[tirofiban|high-bolus dose tirofiban]]), whether or not patients were pretreated with [[ST elevation myocardial infarction thienopyridine therapy|clopidogrel]].<ref name="pmid15066943">{{cite journal |author=Antoniucci D, Migliorini A, Parodi G, Valenti R, Rodriguez A, Hempel A, Memisha G, Santoro GM |title=Abciximab-supported infarct artery stent implantation for acute myocardial infarction and long-term survival: a prospective, multicenter, randomized trial comparing infarct artery stenting plus abciximab with stenting alone|journal=[[Circulation]] |volume=109 |issue=14 |pages=1704–6 |year=2004 |month=April |pmid=15066943|doi=10.1161/01.CIR.0000126284.40075.98 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15066943 |accessdate=2011-12-14}}</ref><ref name="pmid10732888">{{cite journal|author=Neumann FJ, Kastrati A, Schmitt C, Blasini R, Hadamitzky M, Mehilli J, Gawaz M, Schleef M, Seyfarth M, Dirschinger J, Schömig A |title=Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction |journal=[[Journal of the American College of Cardiology]]|volume=35 |issue=4 |pages=915–21 |year=2000 |month=March |pmid=10732888 |doi=|url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(99)00635-X|accessdate=2011-12-14}}</ref><ref name="pmid11919304">{{cite journal |author=Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Carroll JD, Rutherford BD, Lansky AJ |title=Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction |journal=[[The New England Journal of Medicine]] |volume=346 |issue=13|pages=957–66 |year=2002 |month=March |pmid=11919304 |doi=10.1056/NEJMoa013404|url=http://dx.doi.org/10.1056/NEJMoa013404 |accessdate=2011-12-14}}</ref><ref name="pmid11419426">{{cite journal |author=Montalescot G, Barragan P, Wittenberg O, Ecollan P, Elhadad S, Villain P, Boulenc JM, Morice MC, Maillard L, Pansiéri M, Choussat R, Pinton P|title=Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction |journal=[[The New England Journal of Medicine]] |volume=344 |issue=25 |pages=1895–903|year=2001 |month=June |pmid=11419426 |doi=10.1056/NEJM200106213442503|url=http://dx.doi.org/10.1056/NEJM200106213442503 |accessdate=2011-12-14}}</ref><ref name="pmid15827315">{{cite journal |author=De Luca G, Suryapranata H, Stone GW, Antoniucci D, Tcheng JE, Neumann FJ, Van de Werf F, Antman EM, Topol EJ |title=Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials |journal=[[JAMA : the Journal of the American Medical Association]] |volume=293 |issue=14|pages=1759–65 |year=2005 |month=April |pmid=15827315 |doi=10.1001/jama.293.14.1759|url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15827315|accessdate=2011-12-14}}</ref><ref name="pmid19332467">{{cite journal |author=Mehilli J, Kastrati A, Schulz S, Früngel S, Nekolla SG, Moshage W, Dotzer F, Huber K, Pache J, Dirschinger J, Seyfarth M, Martinoff S, Schwaiger M, Schömig A |title=Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial |journal=[[Circulation]] |volume=119 |issue=14|pages=1933–40 |year=2009 |month=April |pmid=19332467 |doi=10.1161/CIRCULATIONAHA.108.818617|url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=19332467|accessdate=2011-12-14}}</ref><ref name="pmid19875386">{{cite journal |author=De Luca G, Navarese E, Marino P |title=Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials |journal=[[European Heart Journal]] |volume=30 |issue=22 |pages=2705–13 |year=2009|month=November |pmid=19875386 |pmc=2777025 |doi=10.1093/eurheartj/ehp118|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=19875386|accessdate=2011-12-14}}</ref> (For [[glycoprotein IIb/IIIa inhibitor]] administration in patients not pretreated with [[ST elevation myocardial infarction thienopyridine therapy|clopidogrel]], ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''; for [[glycoprotein IIb/IIIa inhibitor]] administration in patients pretreated with [[ST elevation myocardial infarction thienopyridine therapy|clopidogrel]],''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'')<nowiki>"</nowiki>
|}


1. Combination pharmacological [[reperfusion]] with [[abciximab]] and half-dose [[reteplase]] or [[tenecteplase]] should not be given to patients aged greater than 75 years because of an increased risk of [[ICH]]. ''(Level of Evidence: B)''
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients undergoing [[ST elevation myocardial infarction primary percutaneous coronary intervention#Primary PCI|primary PCI]] with [[abciximab]], it may be reasonable to administer [[abciximab|intracoronary abciximab]].<ref name="pmid19332467">{{cite journal |author=Mehilli J, Kastrati A, Schulz S, Früngel S, Nekolla SG, Moshage W, Dotzer F, Huber K, Pache J, Dirschinger J, Seyfarth M, Martinoff S, Schwaiger M, Schömig A |title=Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial |journal=[[Circulation]] |volume=119|issue=14 |pages=1933–40 |year=2009 |month=April |pmid=19332467|doi=10.1161/CIRCULATIONAHA.108.818617 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=19332467 |accessdate=2011-12-14}}</ref><ref name="pmid15170708">{{cite journal|author=Bellandi F, Maioli M, Gallopin M, Toso A, Dabizzi RP |title=Increase of myocardial salvage and left ventricular function recovery with intracoronary abciximab downstream of the coronary occlusion in patients with acute myocardial infarction treated with primary coronary intervention|journal=[[Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions]] |volume=62 |issue=2 |pages=186–92 |year=2004 |month=June|pmid=15170708 |doi=10.1002/ccd.20041 |url=http://dx.doi.org/10.1002/ccd.20041|accessdate=2011-12-14}}</ref><ref name="pmid16274764">{{cite journal |author=Romagnoli E, Burzotta F, Trani C, Mazzari MA, Biondi-Zoccai GG, De Vita M, Giannico F, Niccoli G, Prati F, Rebuzzi AG, Mongiardo R, Crea F |title=Angiographic evaluation of the effect of intracoronary abciximab administration in patients undergoing urgent PCI |journal=[[International Journal of Cardiology]]|volume=105 |issue=3 |pages=250–5 |year=2005 |month=December |pmid=16274764|doi=10.1016/j.ijcard.2004.11.037|url=http://linkinghub.elsevier.com/retrieve/pii/S0167-5273(05)00270-6|accessdate=2011-12-14}}</ref><ref name="pmid20066137">{{cite journal |author=Iversen A, Galatius S, Jensen JS |title=The Optimal Route of Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Abciximab During Percutaneous Coronary Intervention; Intravenous Versus Intracoronary|journal=[[Current Cardiology Reviews]] |volume=4 |issue=4 |pages=293–9 |year=2008 |month=November|pmid=20066137 |pmc=2801861 |doi=10.2174/157340308786349480 |url= |accessdate=2011-12-14}}</ref><ref name="pmid19736089">{{cite journal |author=Wöhrle J, Nusser T, Mayer C, Kochs M, Hombach V|title=Intracoronary application of abciximab in patients with ST-elevation myocardial infarction|journal=[[EuroIntervention : Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology]] |volume=3 |issue=4 |pages=465–9|year=2008 |month=January |pmid=19736089 |doi= |url= |accessdate=2011-12-14}}</ref><ref name="pmid14696156">{{cite journal |author=Kakkar AK, Moustapha A, Hanley HG, Weiss M, Caldito G, Misra P, Reddy PC, Tandon N |title=Comparison of intracoronary vs. intravenous administration of abciximab in coronary stenting |journal=[[Catheterization and Cardiovascular Interventions :Official Journal of the Society for Cardiac Angiography & Interventions]] |volume=61 |issue=1|pages=31–4 |year=2004 |month=January |pmid=14696156 |doi=10.1002/ccd.10730|url=http://dx.doi.org/10.1002/ccd.10730 |accessdate=2011-12-14}}</ref><ref name="pmid20494655">{{cite journal |author=Bertrand OF, Rodés-Cabau J, Larose E, Rinfret S, Gaudreault V, Proulx G, Barbeau G, Déry JP, Gleeton O, Manh-Nguyen C, Noël B, Roy L, Costerousse O, De Larochellière R |title=Intracoronary compared to intravenous Abciximab and high-dose bolus compared to standard dose in patients with ST-segment elevation myocardial infarction undergoing transradial primary percutaneous coronary intervention: a two-by-two factorial placebo-controlled randomized study |journal=[[The American Journal of Cardiology]] |volume=105 |issue=11 |pages=1520–7|year=2010 |month=June |pmid=20494655 |doi=10.1016/j.amjcard.2010.01.006|url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(10)00092-5|accessdate=2011-12-14}}</ref><ref name="pmid12682003">{{cite journal |author=Wöhrle J, Grebe OC, Nusser T, Al-Khayer E, Schaible S, Kochs M, Hombach V, Höher M |title=Reduction of major adverse cardiac events with intracoronary compared with intravenous bolus application of abciximab in patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty|journal=[[Circulation]] |volume=107 |issue=14 |pages=1840–3 |year=2003 |month=April |pmid=12682003|doi=10.1161/01.CIR.0000066852.98038.D1 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12682003 |accessdate=2011-12-14}}</ref><ref name="pmid16786232">{{cite journal|author=Deibele AJ, Kirtane AJ, Pinto DS, Lucca MJ, Neva C, Shui A, Murphy SA, Tcheng JE, Gibson CM|title=Intracoronary bolus administration of eptifibatide during percutaneous coronary stenting for non ST elevation myocardial infarction and unstable angina |journal=[[Journal of Thrombosis and Thrombolysis]] |volume=22 |issue=1 |pages=47–50 |year=2006 |month=August |pmid=16786232|doi=10.1007/s11239-006-7454-8 |url=http://dx.doi.org/10.1007/s11239-006-7454-8|accessdate=2011-12-14}}</ref><ref name="pmid17711710">{{cite journal |author=Yang XC, Zhang DP, Wang LF, Xu L, Ge YG, Wang HS, Li WM, Ni ZH, Xia K, Lian Y, Xue YL, Ma LX |title=[Effects of intracoronary or intravenous tirofiban administration in patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention] |language=Chinese|journal=[[Zhonghua Xin Xue Guan Bing Za Zhi]] |volume=35 |issue=6 |pages=517–22 |year=2007|month=June |pmid=17711710 |doi= |url= |accessdate=2011-12-14}}</ref><ref name="pmid20516508">{{cite journal |author=Hansen PR, Iversen A, Abdulla J |title=Improved clinical outcomes with intracoronary compared to intravenous abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a systematic review and meta-analysis |journal=[[The Journal of Invasive Cardiology]] |volume=22 |issue=6 |pages=278–82 |year=2010 |month=June |pmid=20516508 |doi=|url=http://www.invasivecardiology.com/articles/Improved-Clinical-Outcomes-with-Intracoronary-Compared-Intravenous-Abciximab-Patients-with-|accessdate=2011-12-14}}</ref><ref name="pmid16790200">{{cite journal |author=Galache Osuna JG, Sánchez-Rubio J, Calvo I, Diarte JA, Lukic A, Placer LJ |title=[Does intracoronary abciximab improve the outcome of percutaneous coronary interventions? A randomized controlled trial]|language=Spanish; Castilian |journal=[[Revista Española De Cardiología]] |volume=59 |issue=6|pages=567–74 |year=2006 |month=June |pmid=16790200 |doi=|url=http://www.revespcardiol.org/en/linksolver/pdf/ivp/0300-8932/59/567|accessdate=2011-12-14}}</ref><ref name="pmid18753700">{{cite journal |author=Wu TG, Zhao Q, Huang WG, Wei JR, Chen SW, Zhao J, Huang LP, Wang LX |title=Effect of intracoronary tirofiban in patients undergoing percutaneous coronary intervention for acute coronary syndrome |journal=[[Circulation Journal : Official Journal of the Japanese Circulation Society]] |volume=72 |issue=10 |pages=1605–9|year=2008 |month=October |pmid=18753700 |doi=|url=http://joi.jlc.jst.go.jp/JST.JSTAGE/circj/CJ-08-0357?from=PubMed|accessdate=2011-12-14}}</ref><ref name="pmid12083481">{{cite journal |author=Marciniak SJ, Mascelli MA, Furman MI, Michelson AD, Jakubowski JA, Jordan RE, Marchese PJ, Frelinger AL |title=An additional mechanism of action of abciximab: dispersal of newly formed platelet aggregates|journal=[[Thrombosis and Haemostasis]] |volume=87 |issue=6 |pages=1020–5 |year=2002 |month=June|pmid=12083481 |doi= |url= |accessdate=2011-12-14}}</ref><ref name="pmid20124127">{{cite journal|author=Deibele AJ, Jennings LK, Tcheng JE, Neva C, Earhart AD, Gibson CM |title=Intracoronary eptifibatide bolus administration during percutaneous coronary revascularization for acute coronary syndromes with evaluation of platelet glycoprotein IIb/IIIa receptor occupancy and platelet function: the Intracoronary Eptifibatide (ICE) Trial |journal=[[Circulation]] |volume=121 |issue=6|pages=784–91 |year=2010 |month=February |pmid=20124127 |doi=10.1161/CIRCULATIONAHA.109.882746|url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=20124127|accessdate=2011-12-14}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
 
===Glycoprotein IIb/IIIa Inhibitors (DO NOT EDIT)<ref name="pmid19923169">{{cite journal| author=Kushner FG, Hand M, Smith SC, King SB, Anderson JL, Antman EM et al.| title=2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2009 | volume= 120 | issue= 22 | pages= 2271-306 | pmid=19923169 | doi=10.1161/CIRCULATIONAHA.109.192663 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19923169  }} </ref>===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' It is reasonable to start treatment with an intravenous glycoprotein (GP) IIb/IIIa receptor antagonist such as [[abciximab]] <ref name="pmid9727542">{{cite journal |author=Brener SJ, Barr LA, Burchenal JE, ''et al.'' |title=Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators |journal=Circulation |volume=98 |issue=8 |pages=734–41 |year=1998 |month=August |pmid=9727542 |doi= |url=}}</ref><ref name="pmid11919304">{{cite journal |author=Stone GW, Grines CL, Cox DA, ''et al.'' |title=Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction |journal=N. Engl. J. Med. |volume=346 |issue=13 |pages=957–66 |year=2002 |month=March |pmid=11919304 |doi=10.1056/NEJMoa013404 |url=}}</ref><ref name="pmid11419426">{{cite journal |author=Montalescot G, Barragan P, Wittenberg O, ''et al.'' |title=Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction |journal=N. Engl. J. Med. |volume=344 |issue=25 |pages=1895–903 |year=2001 |month=June |pmid=11419426 |doi=10.1056/NEJM200106213442503 |url=}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' high bolus-dose [[tirofiban]] <ref name="pmid20510211">{{cite journal |author=ten Berg JM, van 't Hof AW, Dill T, ''et al.'' |title=Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome |journal=J. Am. Coll. Cardiol. |volume=55 |issue=22 |pages=2446–55 |year=2010 |month=June |pmid=20510211 |doi=10.1016/j.jacc.2009.11.091 |url=}}</ref><ref name="pmid18375998">{{cite journal |author=Valgimigli M, Campo G, Percoco G, ''et al.'' |title=Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial |journal=JAMA |volume=299 |issue=15 |pages=1788–99 |year=2008 |month=April |pmid=18375998 |doi=10.1001/jama.299.15.joc80026 |url=}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' or double-bolus eptifibatide <ref name="pmid20670756">{{cite journal |author=Akerblom A, James SK, Koutouzis M, ''et al.'' |title=Eptifibatide is noninferior to abciximab in primary percutaneous coronary intervention: results from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) |journal=J. Am. Coll. Cardiol. |volume=56 |issue=6 |pages=470–5 |year=2010 |month=August |pmid=20670756 |doi=10.1016/j.jacc.2009.10.093 |url=}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' at the time of primary PCI (with or without stenting or clopidogrel pretreatment) in selected patients with [[STEMI]] who are receiving unfractionated heparin (UFH).<nowiki>"</nowiki>
|}
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The usefulness of glycoprotein IIb/IIIa receptor antagonists (as part of a preparatory pharmacological strategy for patients with STEMI before their arrival in the cardiac catheterization laboratory for angiography and PCI) is uncertain. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}
 
===Combination Therapy With Glycoprotein IIb/IIIa Inhibitors (DO NOT EDIT) <ref name="pmid15289388">{{cite journal| author=Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M et al.| title=ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). | journal=Circulation | year= 2004 | volume= 110 | issue= 5 | pages= 588-636 | pmid=15289388 | doi=10.1161/01.CIR.0000134791.68010.FA | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15289388  }} </ref>===
 
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]]
|-
|bgcolor="LightCoral"|
<nowiki>"</nowiki>'''1.''' Combination pharmacological [[reperfusion]] with [[abciximab]] and half-dose [[reteplase]] or [[tenecteplase]] should not be given to patients aged greater than 75 years because of an increased risk of [[ICH]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Combination pharmacological [[reperfusion]] with [[abciximab]] and half-dose [[reteplase]] or [[tenecteplase]] may be considered for prevention of reinfarction ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' and other complications of [[STEMI]] in selected patients: [[anterior]] location of [[MI]], age less than 75 years, and no risk factors for bleeding. In two clinical trials of combination [[reperfusion]], the prevention of reinfarction did not translate into a survival benefit at either 30 days or 1 year. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' Combination pharmacological [[reperfusion]] with [[abciximab]] and half-dose [[reteplase]] or [[tenecteplase]] may be considered for prevention of reinfarction and other complications of [[STEMI]] in selected patients: [[anterior]] location of [[MI]], age less than 75 years, and no risk factors for bleeding in whom an early referral for [[angiography]] and [[PCI]] (i.e., [[facilitated PCI]]) is planned. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}


==Sources==
==Sources==
*The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction <ref name="pmid15339869">{{cite journal |author=Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK |title=ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction) |journal=Circulation |volume=110 |issue=9 |pages=e82–292 |year=2004 |month=August |pmid=15339869 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15339869}}</ref>
*The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction <ref name="pmid15339869">{{cite journal |author=Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK |title=ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction) |journal=Circulation |volume=110 |issue=9|pages=e82–292 |year=2004|month=August |pmid=15339869 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15339869}}</ref>


*The 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction <ref name="pmid18071078">{{cite journal |author=Antman EM, Hand M, Armstrong PW, ''et al'' |title=2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee |journal=Circulation |volume=117 |issue=2 |pages=296–329 |year=2008 |month=January |pmid=18071078 |doi=10.1161/CIRCULATIONAHA.107.188209 |url=}}</ref>
*2013 Revised ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction<ref name="pmid23247303">{{cite journal |author=O'Gara PT, Kushner FG, Ascheim DD, ''et al.'' |title=2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines |journal=Circulation |volume= |issue= |pages= |year=2012 |month=December |pmid=23247303|doi=10.1161/CIR.0b013e3182742c84 |url=}}</ref>


==References==
==References==
{{reflist|2}}
{{reflist|2}}


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Latest revision as of 19:16, 8 November 2016

Acute Coronary Syndrome Main Page

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Other Antiplatelet Agents Including Aspirin and Thienopyridines

There is clear data demonstrating the benefits of the antiplatelets aspirin[1] and thienopyridenes [2] in the management of patients with ST elevation MI treated with fibrinolytic administration. The benefits of clopidogrel vs placebo in patients undergoing primary angioplasty have not been established in randomized trials, although non-randomized registry data is consistent with a benefit of clopidogrel in this setting. The benefit of aspirin plus thienopyridine therapy versus aspirin monotherapy alone could be difficult to establish in randomized trials given that the majority of STEMI patients are treated with a stent which in turn obviates chronic thienopyridine treatment. Despite the required chronic thienopyridine therapy following stent placement, the slower onset of action of oral thienopyridines relative to that of parenteral antiplatelet agents such as glycoprotein IIb/IIIa inhibitors raises important questions as to the acute / early benefits of glycoprotein IIb/IIIa inhibitors versus thienopyridines. Furthermore, the optimal timing of thienopyridine therapy in primary PCI is not well established. In so far a few patients undergo coronary artery bypass grafting (CABG) surgery urgently in the setting of STEMI, the need to define the anatomy prior to theinopyridine administration may not be as compelling as it is in the setting of stable angina, unstable angina and non-ST elevation MI.

Current guidelines recommend pre-loading with 300 to 600 mg of clopidogrel in the primary PCI setting. Again, it should be emphasized that this is not based upon randomized trial data enrolling STEMI patients undergoing primary PCI, but rather from data originating from non-randomized subgroup analyses and registries. One registry demonstrated that pre-loading with clopidogrel in the setting of STEMI was associated with a 2.2 fold improvement in normal TIMI myocardial perfusion grade 3 (O.R. 1.2-3.9, p=0.01) was well as a reduced risk of recurrent MI (0% vs 3.2%, respectively, p= 0.04) [3]. In a subgroup of 2707 patients managed with primary PCI in the Acute Coronary Syndromes (ACOS) registry, 1 year mortality was significantly reduced among patients treated with aspirin plus clopidogrel versus aspirin alone (OR 0.38, 95% CI 0.23-0.62]. It should be noted that this data is limited by the fact that neither the loading dose nor timing of clopidogrel were reported [4]. It should also be realized that in registries, clopidogrel administration is often a surrogate or a marker of the use of a stent, and it is not clear whether the benefit was mediated by the stent or by the clopidogrel. Finally, Gibson et al in a substudy from CLARITY have demonstrated that non-emergent PCI after fibrinolytic therapy was associated with improved mortality among patients randomized to clopidogrel (OR 0.34, 95% CI 0.13-0.92, P = .034) but not placebo (OR 1.41, 95% CI 0.63-3.19, P = .40, interaction P = .028)[5].

Glycoprotein IIb/IIIa Inhibition

Glycoprotein IIb/IIIa inhibitors are a third class of antiplatelet agents that have, in contrast to aspirin and clopidogrel, been studied extensively in the setting of STEMI treated with primary PCI. Meta analyses of randomized trial data do support a clinical event reduction (including a strong trend toward a mortality reduction) among STEMI patients treated with GPIIb/IIIa inhibitors [6][7]. In contrast to primary PCI, there is no clinical benefit of GPIIb/IIIa inhibition when added to the administration of a full dose of a fibrinolytic agent when co-administered at the time of presentation with STEMI. This combination is clearly associated with increased bleeding, particularly in the elderly [8]. The benefit of glycoprotein IIb/IIIa administration in the cardiac catheterization laboratory several hours after fibrinolytic administration is supported by non-randomized observational data [9][10].

There are several clinical questions regarding GP IIb/IIIa inhibition in the setting of STEMI that have not been definitively resolved in randomized trials:

  1. What is the optimal timing of GP IIb/IIIa inhibitors in STEMI? Is it before cardiac catheterization which may improve patency on arrival to the cardiac catheterization laboratory or is at the time of percutaneous coronary intervention (PCI)?
  2. What is the optimal route of GP IIb/IIIa inhibitors in STEMI? Is it via the intravenous route early, or via the intracoronary route once the anatomy has been defined.
  3. What is the optimal duration of GP IIb/IIIa inhibition? Longer durations of infusion may be associated with greater efficacy but also with more bleeding.
  4. What is the role of GP IIb/IIIa inhibitors in STEMI in the context of bivalirudin therapy?
  5. What is the role of GP IIb/IIIa inhibitors in STEMI in the context of more potent antiplatelet agents that may become available.

Mechanism of Benefit of Glycoprotein IIb/IIIa Inhibition

Glycoprotein IIb/IIIa inhibition blocks the cross-linking of fibrin strands to the platelet at the glycoprotein IIb/IIIa receptor. GPIIb/IIIa inhibition blocks the formation of new thrombus in this fashion, but high levels of inhibition have been associated with disaggregation of pre-existing clot [11][12][13][14].

Among STEMI patients, Gibson et al have demonstrated that a greater number of glycoprotein IIb/IIIa receptors occupied is associated with improved myocardial perfusion, ST segment resolution and coronary blood flow [15][16].

Among patients with ST elevation myocardial infarction, treatment with GPIIb/IIIa inhibitors has been associated with improved epicardial patency (TIMI 3 flow improves from approximately 15% to 30%) and improved myocardial perfusion on arrival to the cardiac catheterization laboratory [17]. Despite these improved rates of flow and perfusion, the isolated use of a GP IIb/IIIa inhibitor does not restore TIMI 3 flow in a sufficient proportion of patients to make it a viable stand alone pharmacologic strategy in the absence of adjunctive PCI. To improve the rate of normal TIMI grade 3 flow on arrival to the cardiac catheterization laboratory, GP IIb/IIIa antagonists have been combined with fibrinolytic agents.[18][19] Despite the improvement in epicardial vessel patency with the combination of these agents, clinical outcomes were not meaningfully improved [8] [20], and the combination of these agents prior to cardiac catheterization for STEMI has largely fallen out of favor.

Clinical Trial Data

Facilitated PCI Using a Glycoprotein IIb/IIIa Inhibitor Alone in the Absence of Fibrinolytic Administration

The glycoprotein IIb/IIIa inhibitors such as the small molecules tirofiban, and eptifibatide as well as the large molecule abciximab have been associated with improved outcomes in primary PCI trials [21] [6]. One issue is the optimal timing of the administration of these agents: should they be administered in the emergency room prior to cardiac catheterization (which may cause a delay in transferring the patient to the cardiac catheterization laboratory), or should they be administered in the cardiac catheterization laboratory which may miss the potential benefit of opening the vessel prior to arrival in the cardiac catheterization laboratory.

Comparisons of Glycoprotein IIb/IIIa Inhibitors

There are few randomized trials directly comparing agents in this class. The Multicentre Evaluation of Single High-Dose Bolus Tirofiban vs. Abciximab With Sirolimus-Eluting Stent or Bare Metal Stent/ in Acute Myocardial Infarction (MULTISTRATEGY) trial compared the small molecule tirofiban with the large molecule abciximab in the management of primary PCI patients [22]. While this was a randomized trial, it was not blinded. All 745 patients were treated with 300 mg of clopidogrel prior to cardiac catheterization. There was a 2 X 2 randomization in the trial. The first level of randomization was to high dose tirofiban (25 μg/kg bolus regimen) versus abciximab, both administered at the time of first medical contact with the patient. The second level of randomization was to either sirolimus-eluting (SES) or bare metal stenting (BMS). Given that only 745 patients were enrolled, a highly powered endpoint was chosen, which was ST segment resolution at 90 minutes following PCI. ST segment resolution associated with tirofiban (85.3%) was statistically non-inferior to abciximab (83.6%)(RR, 1.020; 97.5% CI, 0.958-1.086; p<0 .001 for noninferiority). Consistent with these EKG findings of non-inferiority, there was likewise no difference in major adverse cardiac events (MACE) for tirofiban vs abciximab at either 30 days (4.0% vs. 4.3%, respectively; p=0.85)or 8 months (9.9% vs. 12.4% respectively; p=0.30. With respect to safety, there was a significant increase in the risk of thrombocytopenia associated with abciximab (0.5% for tirofiban versus 2.4% for abciximab: 2.4%; p=0.03). The increased risk of thrombocytopenia associated with abciximab has been consistently observed across multiple trials[23].

In a smaller earlier trial called STRATEGY (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction), the same investigators compared the outcomes among STEMI patients treated with high-dose tirofiban plus a sirolimus-eluting stent (n = 87) versus abciximab plus a bare metal stent (n = 88) [24]. The hypothesis was that administration of tirofiban instead of abciximab would allow the expanded use of drug eluting stents by nullifying the cost differential between sirolimus-eluting vs bare-metal stents. The primary endpoint of death, nonfatal myocardial infarction, stroke, or binary restenosis at 8 months occurred in 19% of tirofiban patients versus 50% of abciximab patients (p<0.001).

A meta-analysis that incorporated randomized trial data from 6 trials involving 2,197 patients through Cotober 2008 indicates that there is no difference in outcomes between primary PCI patients treated with abciximab versus either high dose tirofiban (5 trials) versus eptifibatide (1 trial) [25] Abciximab was not associated with an improvement in either the rate of TIMI flow grade 3 post PCI (89.8% vs. 89.1%, p = 0.72) or ST-segment resolution following PCI (67.8% vs. 68.2%, p = 0.66). Likewise, abciximab was not associated with a reduction in either 30-day mortality (2.2% vs. 2.0%, p = 0.66) or reinfarction (1.2% vs. 1.2%, p = 0.88). No difference in bleeding was observed.

Facilitated PCI Trials using Tirofiban

Early upstream administration of tirofiban has been associated with better pre-PCI angiographic outcomes, but these studies were not sufficiently powered to demonstrate significant clinical benefit. The benefit of early administration of tirofiban compared to upstream administration was assessed in the TIGER-PA trial (TIrofiban Given in the Emergency Room before Primary Angioplasty). This study consisted of 100 patients who received tirofiban either in the ER or in the cath lab. There was a significant improvement in the initial angiographic parameters such as TIMI flow grade (TFG), corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG). This study was not powered to demonstrate a significant clinical benefit [26].

Likewise, the investigators from the On-TIME trial (Ongoing Tirofiban in myocardial infarction Evaluation) evaluated a similar strategy of administration of tirofiban approximately one hour before PCI compared to administration of tirofiban in the cath lab [27]. The primary endpoint of TIMI grade 3 flow pre-PCI was not increased with the use of early tirofiban (19% vs. 15%, p=0.22), but TIMI grade 2 and 3 flow combined, thrombus burden and myocardial perfusion were improved. This study also was not powered to demonstrate a clinical benefit.

In contrast to the above two studies, another small trial (RAPIER) demonstrated that the upstream use of tirofiban in the ER was not associated with a significant improvement in the rate of TIMI grade 2 or 3 flow compared with the delayed administration of tirofiban in the cardiac catheterization laboratory (39% vs. 27% p >0.2). There was, however, a trend towards improved ST segment resolution in the ER group (69% vs.77%, p=0.07) [28].

Facilitated PCI Trials using Abciximab

The use of abciximab in the emergency room (ER) has likewise been compared to delayed administration in the cardiac catheterization laboratory. The RELax-AMI study (Randomized Early versus Late abciximab in Acute Myocardial Infarction treated with primary coronary intervention) included 210 patients with acute ST segment elevation myocardial infarction. Of these 105 patients received abciximab in the ER and the remaining 105 received abciximab in the cardiac catheterization laboratory. This study demonstrated significant improvements in the pre-PCI angiographic parameters including TIMI grade 3 flow (24% vs. 10%, p=0.01), corrected TIMI frame count (78±30 vs. 92±21, p=0.001) and myocardial blush grade (MBG 2/3) [15% vs. 6%, p=0.02] in the early abciximab group compared to the upstream group. The post-PCI ST segment resolution (>70%) was greater in the early abciximab group (50% vs. 35%, p=0.03) and the myocardial blush grade following PCI was also improved (MBG 2/3 79% vs. 58%, p=0.001). The one month ejection fraction was significantly better in the early group [29].

Similarly, the ERAMI trial (Early Reopro Administration in Myocardial Infarction) demonstrated significant improvements in the post PCI CTFC and increased rate of normal TIMI Myocardial Perfusion Grade 3 among patients who received abciximab in the ER compared to those who received it in the cath lab despite an absence of any difference in pre-PCI angiographic parameters [30].

Multiple other studies have demonstrated similar improvements in angiographic outcomes associated with early administration. Zorman et al demonstrated that ER administration of abciximab resulted in increased patency rates, improved ST segment resolution, and better survival compared to administration of abciximab in the cath lab [31]. Bellandi et al demonstrated not only an increase in the rate of TIMI grade 3 flow and improved TIMI Frame Count / myocardial blush grade but also left ventricular function recovery compared to delayed abciximab administration in the cardiac catheterization laboratory [32]. Finally, the ReoPro- BRIDGING study also demonstrated that early administration of abciximab was associated with increased patency of infarct arteries and improved myocardial perfusion [33].

Facilitated PCI Trials using Eptifibatide

Comparable to studies using tirofiban and abciximab, in the INTAMI study (INTegrilin in Acute Myocardial Infarction), Zeymer et al demonstrated that administration of eptifibatide in the ER was associated increased TFG 3 pre PCI compared to administration in the cath lab (34% vs. 10%, p=0.01) [34]. But there was no difference in the TFG 3 post-PCI, death, reinfarction, stroke and major bleed up to 30 days.

The TITAN TIMI-34 (Time to Integrilin Therapy in Acute Myocardial Infarction) was a larger trial than the INTAMI trial consisting of a total of 343 STEMI patients of which 180 received eptifibatide in the ER compared to 163 who received the drug in the cath lab. The primary endpoint, pre PCI corrected TIMI frame count was significantly better in the ER group compared to the cath lab group (77.5±32.2 vs. 84.3±30.7, p=0.049). The pre PCI TMPG 3 was more frequently seen in the ER group (24% vs. 14%, p=0.026). However there was no difference in the bleeding events and clinical outcomes between the two groups [17].

Facilitated PCI Trials Combining Low Dose Fibrinolytic Agent and Glycoprotein IIb/IIIa Inhibitor

Given the discrepancies in the outcomes in facilitated PCI using fibrinolytic alone and glycoprotein IIb/IIIa inhibitor alone, a strategy of combined therapy using low dose fibrinolytic and full dose glycoprotein IIb/IIIa inhibitor was examined. The Strategies for Patency Enhancement in the Emergency Department (SPEED-GUSTO-4 Pilot trial) examined the benefit of administration of fibrinolytic with or without abciximab among patients undergoing early PCI following an acute MI. This non randomized study demonstrated that administration of a half-dose reteplase and abciximab was safe and effective. This strategy was associated with TIMI flow grade 3 in 86% of cases at 90 minutes and the composite end point of death, reinfarction and urgent revascularization occurred in 5.6% of cases in the PCI group compared to 16% in those who did not undergo PCI[35].

The Alteplase and Tirofiban in Acute Myocardial Infarction (ATAMI), a small single center study demonstrated that there was significantly high rates of TIMI grade 2/3 flow among STEMI patients randomized to combination therapy with 50mg alteplase and tirofiban prior to planned PCI compared to upstream administration of tirofiban in the catheter laboratory (87% vs. 42%, p<0.0001). These groups were compared with a matched control patients who underwent PCI with provisional abciximab in the cath lab (29% of patients had TIMI flow grade 2/3). The 30-day mortality was significantly lower in the combination therapy group compared to upstream tirofiban group and the control group (0.7% vs. 5.5%, p<0.02 vs. 6.3%). There were no differences in the incidence of bleeding events between the three groups[36]. This study has its limitations given the fact that this was a single center study with relatively small number of patients and a lower dose of tirofiban was used (10μg/kg).

Contrary to the SPEED and the ATAMI studies, the BRAVE (Bavarian Reperfusion Alternatives Evaluation) study by Kastrati and coworkers was an open label, randomized multi-center study in which the beneficial effect of the use of half dose reteplase and abciximab on the infarct size using single photon emission tomography (SPECT) was examined. The investigators did not demonstrate any improvement in the final infarct size using the combination therapy (n=125) compared to abciximab alone (n=128) among STEMI patients referred for PCI (mean difference in the infarct size was 1.3% between the two groups). There was no difference in the secondary endpoints such as death, reinfarction or stroke [37]. A similar strategy was examined in APAMIT (Asia Pacific Myocardial Infarction Trial) where all STEMI patients received abciximab and were randomized to either immediate PCI or to PCI sixty minutes later following the administration of alteplase. Like all previous studies this study demonstrated that facilitation with a lytic in addition to abciximab was associated with an increase TFG 3 pre PCI but no difference in the clinical outcomes[38].

Given the small sample size in the above studies, another randomized study, the ADVANCE-MI (ADressing the Value of facilitated Angioplasty after Combination therapy or Eptifibatide monotherapy in acute Myocardial Infarction) study was designed to answer similar questions whether a strategy of combination fibrinolytic and a different glycoprotein IIb/IIIa inhibitor (eptifibatide) compared to eptifibatide + placebo prior to PCI would improve clinical outcomes. Although this study originally planned to recruit 5640 patients, it was prematurely terminated because of slow recruitment. An analysis of a total of 148 patients suggested that combination therapy (reduced dose tenecteplase and eptifibatide) was associated with improved epicardial flow and myocardial tissue perfusion on pre-PCI angiography. This strategy however resulted in a trend towards an increase in adverse outcomes (death, new/worsening heart failure or bleeding) compared to eptifibatide + placebo group[39].

The FINESSE trial (the largest trial on combination therapy) results were presented in the European Society of Cardiology meetings in 2007 (www.escardio.org). The Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) study is a 3000-patient, prospective, multicenter, randomized, double-blind, placebo-controlled trial. The study was designed to compare the efficacy and safety of early administration of reduced-dose reteplase and abciximab combination therapy or abciximab alone followed by PCI with abciximab alone administered just before PCI for acute STEMI. Patients were randomized to one of the two facilitated PCI treatments or primary PCI in a 1:1:1 fashion[40]. At 90 days, there were no differences between treatment arms for the primary composite end points of the trial: all-cause mortality, readmission for heart failure, ventricular fibrillation, or cardiogenic shock [10.7% (PCI only group, n=806) vs. 10.5% (abciximab facilitated group, n=818) vs. 9.8% (reteplase and abciximab group, n=828)]. There were also no differences in all-cause mortality (4.5% vs. 5.5% vs. 5.2% respectively), complications of MI (8.9% vs. 7.5% vs. 7.4%), or any of the independent components of the primary composite end point. For safety end points, rates of TIMI major bleeding and minor bleeding were significantly higher for the abciximab/lytic facilitated PCI strategy as compared with primary PCI (14.5% vs. 6.9%, p<0.001). There was also a strong trend towards increased intracranial hemorrhage through discharge or day seven in the combined abciximab/lytic facilitation approach.

More recently, although not truly a facilitated PCI study, the CARESS-in-AMI (Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction) study determined whether early transfer for PCI following pharmacotherapy administration improves outcomes compared to a conservative watchful waiting approach among patients with STEMI with anticipated delay in primary PCI due to their presentation to a non-PCI center[41]. Six hundred patients in this study were pretreated with aspirin, heparin, half dose reteplase and abciximab. Subsequently patients were randomized to either immediate transfer for PCI or transfer only in case of failed reperfusion or clinical deterioration. The investigators demonstrated that there was significant benefit in terms of reduction in 30-day mortality with the immediate transfer strategy (4.4% vs. 10.7%, p=0.004) without any differences in the bleeding events. It is important to note that the CARESS-in-AMI study determines whether early PCI improves pharmacotherapy outcomes. This is in contrast to the facilitated PCI strategy where pharmacotherapy is administered to improve PCI outcomes.

Use of Glycoprotein IIb/IIIa Inhibitors in Rescue PCI Following Failed Fibrinolysis

In contrast to primary PCI, there is no clinical benefit of GPIIb/IIIa inhibition when added to the administration of a full dose of a fibrinolytic agent when co-administered at the time of presentation with STEMI. This combination is clearly associated with increased bleeding, particularly in the elderly [8]. The benefit of glycoprotein IIb/IIIa administration in the cardiac catheterization laboratory several hours after fibrinloytic administration is supported by non-randomized observational data [42][10]. In a small non-randomized study of 59 consecutive patients at a single institution, death, reinfarction and urgent target vessel revascularization was significantly lower among patients treated with GP IIb/IIIa inhibition as compared with patients who were not treated (3.4% vs. 26.7%; p = 0.01).

Side Effects and Complications of GP IIb/IIIa Inhibitors

Thrombocytopenia

Abciximab has consistently been associated with the development of thrombocytopenia [23]. In one meta-analysis, abciximab but not small molecule GP IIb/IIIa inhibitors was associated with an increased risk of mild thrombocytopenia when compared to placebo (4.2% vs 2.0%; P <.001; odds ratio 2.14) as well as severe thrombocytopenia as compared with placebo (1.0% vs 0.4%; P =.01; odds ratio 2.48). Thrombocytipenia has been in turn associated with an increase risk of major bleeding, transfusion, recurrent MI, stroke and both in-hosptial and 30 day mortality [43][44][45][46]

2013 Revised, 2009 and 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction and 2011 ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention, (DO NOT EDIT)[47][48][49][50]

Intravenous Antiplatelet Therapy in Patients of ST-Elevation Myocardial Infarction (STEMI) (DO NOT EDIT)[47][48]

Class III (No Benefit)
"1. Routine pre-catheterization laboratory (e.g., ambulance or emergency room) administration of glycoprotein IIb/IIIa inhibitors as part of an upstream strategy for patients with STEMI undergoing PCI is not beneficial.[6][29][51][52][53][54][55][56] (Level of Evidence: B)"
Class IIa
"1. In patients undergoing primary PCI treated with unfractionated heparin (UFH), it is reasonable to administer a glycoprotein IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban), whether or not patients were pretreated with clopidogrel.[57][58][59][60][21][61][62] (For glycoprotein IIb/IIIa inhibitor administration in patients not pretreated with clopidogrel, (Level of Evidence: A); for glycoprotein IIb/IIIa inhibitor administration in patients pretreated with clopidogrel,(Level of Evidence: C))"
Class IIb
"1. In patients undergoing primary PCI with abciximab, it may be reasonable to administer intracoronary abciximab.[61][63][64][65][66][67][68][69][70][71][72][73][74][11][16] (Level of Evidence: B)"

Glycoprotein IIb/IIIa Inhibitors (DO NOT EDIT)[49]

Class IIa
"1. It is reasonable to start treatment with an intravenous glycoprotein (GP) IIb/IIIa receptor antagonist such as abciximab [75][59][60] (Level of Evidence: A) high bolus-dose tirofiban [53][22](Level of Evidence: B) or double-bolus eptifibatide [76] (Level of Evidence: B) at the time of primary PCI (with or without stenting or clopidogrel pretreatment) in selected patients with STEMI who are receiving unfractionated heparin (UFH)."
Class IIb
"1. The usefulness of glycoprotein IIb/IIIa receptor antagonists (as part of a preparatory pharmacological strategy for patients with STEMI before their arrival in the cardiac catheterization laboratory for angiography and PCI) is uncertain. (Level of Evidence: B) "

Combination Therapy With Glycoprotein IIb/IIIa Inhibitors (DO NOT EDIT) [50]

Class III

"1. Combination pharmacological reperfusion with abciximab and half-dose reteplase or tenecteplase should not be given to patients aged greater than 75 years because of an increased risk of ICH. (Level of Evidence: B)"

Class IIb
"1. Combination pharmacological reperfusion with abciximab and half-dose reteplase or tenecteplase may be considered for prevention of reinfarction (Level of Evidence: A) and other complications of STEMI in selected patients: anterior location of MI, age less than 75 years, and no risk factors for bleeding. In two clinical trials of combination reperfusion, the prevention of reinfarction did not translate into a survival benefit at either 30 days or 1 year. (Level of Evidence: B)"
"2. Combination pharmacological reperfusion with abciximab and half-dose reteplase or tenecteplase may be considered for prevention of reinfarction and other complications of STEMI in selected patients: anterior location of MI, age less than 75 years, and no risk factors for bleeding in whom an early referral for angiography and PCI (i.e., facilitated PCI) is planned. (Level of Evidence: C)"

Sources

  • The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction [77]
  • 2013 Revised ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction[47]

References

  1. ↑ "Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group". Lancet. 2 (8607): 349–60. 1988. PMID 2899772. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  2. ↑ Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, Collins R, Liu LS (2005). "Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial". Lancet. 366 (9497): 1607–21. doi:10.1016/S0140-6736(05)67660-X. PMID 16271642. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  3. ↑ Lev EI, Kornowski R, Vaknin-Assa H, Brosh D, Fuchs S, Battler A, Assali A.. Effect of clopidogrel pretreatment on angiographic and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-elevation acute myocardial infarction. Am J Cardiol. 2008;101(4):435-9.
  4. ↑ Zeymer U, Gitt AK, Jünger C, Heer T, et al. Effect of clopidogrel on 1-year mortality in hospital survivors of acute ST-segment elevation myocardial infarction in clinical practice. Eur Heart J. 2006;27(22):2661-6.
  5. ↑ Gibson CM, Murphy SA, Pride YB, Kirtane AJ, Aroesty JM, Stein EB, Ciaglo LN, Southard MC, Sabatine MS, Cannon CP, Braunwald E (2008). "Effects of pretreatment with clopidogrel on nonemergent percutaneous coronary intervention after fibrinolytic administration for ST-segment elevation myocardial infarction: a Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 study". American Heart Journal. 155 (1): 133–9. doi:10.1016/j.ahj.2007.08.034. PMID 18082504. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  6. ↑ 6.0 6.1 6.2 Montalescot G, Borentain M, Payot L, Collet JP, Thomas D (2004). "Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis". JAMA : the Journal of the American Medical Association. 292 (3): 362–6. doi:10.1001/jama.292.3.362. PMID 15265852. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  7. ↑ Montalescot G, Antoniucci D, Kastrati A, Neumann FJ, Borentain M, Migliorini A, Boutron C, Collet JP, Vicaut E (2007). "Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients' data with long-term follow-up". European Heart Journal. 28 (4): 443–9. doi:10.1093/eurheartj/ehl472. PMID 17251257. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  8. ↑ 8.0 8.1 8.2 Topol EJ (2001). "Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial". Lancet. 357 (9272): 1905–14. PMID 11425410. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  9. ↑ Roe MT, Giugliano RP, Tuttle R, Hasselbad V, Murphy SA, Antman EM, Ohman EM, Harrington RA, Granger CB, Mahaffey KW, Cannon CP, Lincoff AM, Gibson CM, Armstrong PW, van de Werf FJ, Califf RM, Topol EJ, Braunwald E. Safety of Adjunctive Glycoprotein IIb/IIIa Blockade During Rescue/Early Percutaneous Coronary Intervention Following Full-Dose Fibrinolytic Therapy for Acute Myocardial Infarction. J Am Coll Cardiol 2003;41(6 Suppl A):332A.
  10. ↑ 10.0 10.1 Gruberg L, Suleiman M, Kapeliovich M, Hammerman H, Grenadier E, Boulus M, Amikam S, Markiewicz W, Beyar R (2006). "Glycoprotein IIb/IIIa inhibitors during rescue percutaneous coronary intervention in acute myocardial infarction". The Journal of Invasive Cardiology. 18 (2): 59–62. PMID 16446517. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  11. ↑ 11.0 11.1 Marciniak SJ, Mascelli MA, Furman MI, Michelson AD, Jakubowski JA, Jordan RE, Marchese PJ, Frelinger AL (2002). "An additional mechanism of action of abciximab: dispersal of newly formed platelet aggregates". Thrombosis and Haemostasis. 87 (6): 1020–5. PMID 12083481. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  12. ↑ Speich HE, Earhart AD, Hill SN, Cholera S, Kueter TJ, Smith JN, White MM, Jennings LK (2009). "Variability of platelet aggregate dispersal with glycoprotein IIb-IIIa antagonists eptifibatide and abciximab". Journal of Thrombosis and Haemostasis : JTH. 7 (6): 983–91. doi:10.1111/j.1538-7836.2009.03432.x. PMID 19548907. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  13. ↑ Moser M, Bertram U, Peter K, Bode C, Ruef J (2003). "Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates". Journal of Cardiovascular Pharmacology. 41 (4): 586–92. PMID 12658060. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  14. ↑ Gibson CM, Buros J, Ciaglo LN, Southard MC, Takao S, Harrigan C, Filopei J, Lew M, Marble SJ, Murphy SA, Cohen MG (2007). "Impact of iodinated contrast injections on percent diameter coronary arterial stenosis and implications for trials of intracoronary pharmacotherapies in patients with ST-elevation myocardial infarction". The American Journal of Cardiology. 100 (1): 13–7. doi:10.1016/j.amjcard.2007.01.068. PMID 17599433. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  15. ↑ Gibson CM, Jennings LK, Murphy SA, Lorenz DP, Giugliano RP, Harrington RA, Cholera S, Krishnan R, Califf RM, Braunwald E (2004). "Association between platelet receptor occupancy after eptifibatide (integrilin) therapy and patency, myocardial perfusion, and ST-segment resolution among patients with ST-segment-elevation myocardial infarction: an INTEGRITI (Integrilin and Tenecteplase in Acute Myocardial Infarction) substudy". Circulation. 110 (6): 679–84. doi:10.1161/01.CIR.0000137912.11655.F6. PMID 15262838. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  16. ↑ 16.0 16.1 Deibele AJ, Jennings LK, Tcheng JE, Neva C, Earhart AD, Gibson CM (2010). "Intracoronary eptifibatide bolus administration during percutaneous coronary revascularization for acute coronary syndromes with evaluation of platelet glycoprotein IIb/IIIa receptor occupancy and platelet function: the Intracoronary Eptifibatide (ICE) Trial". Circulation. 121 (6): 784–91. doi:10.1161/CIRCULATIONAHA.109.882746. PMID 20124127. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  17. ↑ 17.0 17.1 Gibson CM, Kirtane AJ, Murphy SA, Rohrbeck S, Menon V, Lins J, Kazziha S, Rokos I, Shammas NW, Palabrica TM, Fish P, McCabe CH, Braunwald E (2006). "Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial". American Heart Journal. 152 (4): 668–75. doi:10.1016/j.ahj.2006.06.003. PMID 16996831. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  18. ↑ Antman EM, Giugliano RP, Gibson CM, McCabe CH, Coussement P, Kleiman NS, Vahanian A, Adgey AA, Menown I, Rupprecht HJ, Van der Wieken R, Ducas J, Scherer J, Anderson K, Van de Werf F, Braunwald E (1999). "Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators". Circulation. 99 (21): 2720–32. PMID 10351964. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  19. ↑ "Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group". Circulation. 101 (24): 2788–94. 2000. PMID 10859283. Unknown parameter |month= ignored (help)
  20. ↑ Lincoff AM, Califf RM, Van de Werf F, Willerson JT, White HD, Armstrong PW, Guetta V, Gibler WB, Hochman JS, Bode C, Vahanian A, Steg PG, Ardissino D, Savonitto S, Bar F, Sadowski Z, Betriu A, Booth JE, Wolski K, Waller M, Topol EJ (2002). "Mortality at 1 year with combination platelet glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction: GUSTO V randomized trial". JAMA : the Journal of the American Medical Association. 288 (17): 2130–5. PMID 12413372. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  21. ↑ 21.0 21.1 De Luca G, Suryapranata H, Stone GW; et al. (2005). "Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials". JAMA. 293 (14): 1759–65. doi:10.1001/jama.293.14.1759. PMID 15827315. Unknown parameter |month= ignored (help)
  22. ↑ 22.0 22.1 Valgimigli M, Campo G, Percoco G, Bolognese L, Vassanelli C, Colangelo S, de Cesare N, Rodriguez AE, Ferrario M, Moreno R, Piva T, Sheiban I, Pasquetto G, Prati F, Nazzaro MS, Parrinello G, Ferrari R (2008). "Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial". JAMA : the Journal of the American Medical Association. 299 (15): 1788–99. doi:10.1001/jama.299.15.joc80026. PMID 18375998. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  23. ↑ 23.0 23.1 Dasgupta H, Blankenship JC, Wood GC, Frey CM, Demko SL, Menapace FJ (2000). "Thrombocytopenia complicating treatment with intravenous glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis". American Heart Journal. 140 (2): 206–11. doi:10.1067/mhj.2000.107554. PMID 10925331. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  24. ↑ Valgimigli M, Percoco G, Malagutti P, Campo G, Ferrari F, Barbieri D, Cicchitelli G, McFadden EP, Merlini F, Ansani L, Guardigli G, Bettini A, Parrinello G, Boersma E, Ferrari R (2005). "Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial". JAMA : the Journal of the American Medical Association. 293 (17): 2109–17. doi:10.1001/jama.293.17.2109. PMID 15870414. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  25. ↑ De Luca G, Ucci G, Cassetti E, Marino P (2009). "Benefits from small molecule administration as compared with abciximab among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-analysis". Journal of the American College of Cardiology. 53 (18): 1668–73. doi:10.1016/j.jacc.2009.01.053. PMID 19406342. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  26. ↑ Lee DP, Herity NA, Hiatt BL; et al. (2003). "Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial". Circulation. 107 (11): 1497–501. PMID 12654606. Unknown parameter |month= ignored (help)
  27. ↑ van 't Hof AW, Ernst N, de Boer MJ; et al. (2004). "Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial". Eur. Heart J. 25 (10): 837–46. doi:10.1016/j.ehj.2004.04.003. PMID 15140531. Unknown parameter |month= ignored (help)
  28. ↑ Cutlip DE, Ricciardi MJ, Ling FS; et al. (2003). "Effect of tirofiban before primary angioplasty on initial coronary flow and early ST-segment resolution in patients with acute myocardial infarction". Am. J. Cardiol. 92 (8): 977–80. PMID 14556878. Unknown parameter |month= ignored (help)
  29. ↑ 29.0 29.1 Maioli M, Bellandi F, Leoncini M, Toso A, Dabizzi RP (2007). "Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial)". J. Am. Coll. Cardiol. 49 (14): 1517–24. doi:10.1016/j.jacc.2006.12.036. PMID 17418289. Unknown parameter |month= ignored (help)
  30. ↑ Gabriel HM, Oliveira JA, da Silva PC, da Costa JM, da Cunha JA (2006). "Early administration of abciximab bolus in the emergency department improves angiographic outcome after primary PCI as assessed by TIMI frame count: results of the early ReoPro administration in myocardial infarction (ERAMI) trial". Catheter Cardiovasc Interv. 68 (2): 218–24. doi:10.1002/ccd.20798. PMID 16817177. Unknown parameter |month= ignored (help)
  31. ↑ Zorman S, Zorman D, Noc M (2002). "Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplasty". Am. J. Cardiol. 90 (5): 533–6. PMID 12208418. Unknown parameter |month= ignored (help)
  32. ↑ Bellandi F, Maioli M, Leoncini M, Toso A, Dabizzi RP (2006). "Early abciximab administration in acute myocardial infarction treated with primary coronary intervention". Int. J. Cardiol. 108 (1): 36–42. doi:10.1016/j.ijcard.2005.04.025. PMID 15927285. Unknown parameter |month= ignored (help)
  33. ↑ Gyöngyösi M, Domanovits H, Benzer W; et al. (2004). "Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion - results of the Austrian multi-centre randomized ReoPro-BRIDGING Study". Eur. Heart J. 25 (23): 2125–33. doi:10.1016/j.ehj.2004.09.018. PMID 15571828. Unknown parameter |month= ignored (help)
  34. ↑ Zeymer U, Zahn R, Schiele R; et al. (2005). "Early eptifibatide improves TIMI 3 patency before primary percutaneous coronary intervention for acute ST elevation myocardial infarction: results of the randomized integrilin in acute myocardial infarction (INTAMI) pilot trial". Eur. Heart J. 26 (19): 1971–7. doi:10.1093/eurheartj/ehi293. PMID 15857851. Unknown parameter |month= ignored (help)
  35. ↑ Herrmann HC, Moliterno DJ, Ohman EM; et al. (2000). "Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial". J. Am. Coll. Cardiol. 36 (5): 1489–96. PMID 11079647. Unknown parameter |month= ignored (help)
  36. ↑ Peters S, Truemmel M, Koehler B (2008). "Facilitated PCI by combination fibrinolysis or upstream tirofiban in acute ST-segment elevation myocardial infarction: results of the Alteplase and Tirofiban in Acute Myocardial Infarction (ATAMI) trial". Int. J. Cardiol. 130 (2): 235–40. doi:10.1016/j.ijcard.2007.08.048. PMID 18055037. Unknown parameter |month= ignored (help)
  37. ↑ Kastrati A, Mehilli J, Schlotterbeck K; et al. (2004). "Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial". JAMA. 291 (8): 947–54. doi:10.1001/jama.291.8.947. PMID 14982910. Unknown parameter |month= ignored (help)
  38. ↑ Wong A, Mak KH, Chan C; et al. (2004). "Combined fibrinolysis using reduced-dose alteplase plus abciximab with immediate rescue angioplasty versus primary angioplasty with adjunct use of abciximab for the treatment of acute myocardial infarction: Asia-Pacific Acute Myocardial Infarction Trial (APAMIT) pilot study". Catheter Cardiovasc Interv. 62 (4): 445–52. doi:10.1002/ccd.20101. PMID 15274152. Unknown parameter |month= ignored (help)
  39. ↑ "Facilitated percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: results from the prematurely terminated ADdressing the Value of facilitated ANgioplasty after Combination therapy or Eptifibatide monotherapy in acute Myocardial Infarction (ADVANCE MI) trial". Am. Heart J. 150 (1): 116–22. 2005. doi:10.1016/j.ahj.2005.04.005. PMID 16084157. Unknown parameter |month= ignored (help)
  40. ↑ Ellis SG, Armstrong P, Betriu A; et al. (2004). "Facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention: design and rationale of the Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) trial". Am. Heart J. 147 (4): E16. doi:10.1016/j.ahj.2003.07.025. PMID 15077099. Unknown parameter |month= ignored (help)
  41. ↑ Di Mario C, Dudek D, Piscione F; et al. (2008). "Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial". Lancet. 371 (9612): 559–68. doi:10.1016/S0140-6736(08)60268-8. PMID 18280326. Unknown parameter |month= ignored (help)
  42. ↑ Roe MT, Giugliano RP, Tuttle R, Hasselbad V, Murphy SA, Antman EM, Ohman EM, Harrington RA, Granger CB, Mahaffey KW, Cannon CP, Lincoff AM, Gibson CM, Armstrong PW, van de Werf FJ, Califf RM, Topol EJ, Braunwald E. Safety of Adjunctive Glycoprotein IIb/IIIa Blockade During Rescue/Early Percutaneous Coronary Intervention Following Full-Dose Fibrinolytic Therapy for Acute Myocardial Infarction. J Am Coll Cardiol 2003;41(6 Suppl A):332A.
  43. ↑ Gore JM, Spencer FA, Gurfinkel EP, López-Sendón J, Steg PG, Granger CB, FitzGerald G, Agnelli G (2009). "Thrombocytopenia in patients with an acute coronary syndrome (from the Global Registry of Acute Coronary Events [GRACE])". The American Journal of Cardiology. 103 (2): 175–80. doi:10.1016/j.amjcard.2008.08.055. PMID 19121432. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  44. ↑ Merlini PA, Rossi M, Menozzi A, Buratti S, Brennan DM, Moliterno DJ, Topol EJ, Ardissino D (2004). "Thrombocytopenia caused by abciximab or tirofiban and its association with clinical outcome in patients undergoing coronary stenting". Circulation. 109 (18): 2203–6. doi:10.1161/01.CIR.0000127867.41621.85. PMID 15117843. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  45. ↑ Nikolsky E, Sadeghi HM, Effron MB, Mehran R, Lansky AJ, Na Y, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Stuckey TD, Turco M, Carroll JD, Grines CL, Stone GW (2005). "Impact of in-hospital acquired thrombocytopenia in patients undergoing primary angioplasty for acute myocardial infarction". The American Journal of Cardiology. 96 (4): 474–81. doi:10.1016/j.amjcard.2005.04.005. PMID 16098296. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  46. ↑ Wang TY, Ou FS, Roe MT, Harrington RA, Ohman EM, Gibler WB, Peterson ED (2009). "Incidence and prognostic significance of thrombocytopenia developed during acute coronary syndrome in contemporary clinical practice". Circulation. 119 (18): 2454–62. doi:10.1161/CIRCULATIONAHA.108.827162. PMID 19398666. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  47. ↑ 47.0 47.1 47.2 O'Gara PT, Kushner FG, Ascheim DD; et al. (2012). "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Circulation. doi:10.1161/CIR.0b013e3182742c84. PMID 23247303. Unknown parameter |month= ignored (help)
  48. ↑ 48.0 48.1 Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH (2011). "2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions" (PDF). Journal of the American College of Cardiology. 58 (24): 2550–83. doi:10.1016/j.jacc.2011.08.006. PMID 22070837. Retrieved 2011-12-08. Text "PDF" ignored (help); Unknown parameter |month= ignored (help)
  49. ↑ 49.0 49.1 Kushner FG, Hand M, Smith SC, King SB, Anderson JL, Antman EM; et al. (2009). "2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Circulation. 120 (22): 2271–306. doi:10.1161/CIRCULATIONAHA.109.192663. PMID 19923169.
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  51. ↑ Keeley EC, Boura JA, Grines CL (2006). "Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials". Lancet. 367 (9510): 579–88. doi:10.1016/S0140-6736(06)68148-8. PMID 16488801. Retrieved 2011-12-12. Unknown parameter |month= ignored (help)
  52. ↑ Van't Hof AW, Ten Berg J, Heestermans T, Dill T, Funck RC, van Werkum W, Dambrink JH, Suryapranata H, van Houwelingen G, Ottervanger JP, Stella P, Giannitsis E, Hamm C (2008). "Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial". Lancet. 372 (9638): 537–46. doi:10.1016/S0140-6736(08)61235-0. PMID 18707985. Retrieved 2011-12-12. Unknown parameter |month= ignored (help)
  53. ↑ 53.0 53.1 ten Berg JM, van 't Hof AW, Dill T, Heestermans T, van Werkum JW, Mosterd A, van Houwelingen G, Koopmans PC, Stella PR, Boersma E, Hamm C (2010). "Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome". Journal of the American College of Cardiology. 55 (22): 2446–55. doi:10.1016/j.jacc.2009.11.091. PMID 20510211. Retrieved 2011-12-12. Unknown parameter |month= ignored (help)
  54. ↑ Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Andersen HR, Betriu A, Savonitto S, Adamus J, Peruga JZ, Hamankiewicz M, Pluta W, Oldroyd K, Ecollan P, Janssens L, Armstrong P, Brodie BR, Herrmann HC, Montalescot G, Neumann FJ, Effron MB, Barnathan ES, Topol EJ (2009). "1-year survival in a randomized trial of facilitated reperfusion: results from the FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) trial". JACC. Cardiovascular Interventions. 2 (10): 909–16. doi:10.1016/j.jcin.2009.07.009. PMID 19850248. Retrieved 2011-12-12. Unknown parameter |month= ignored (help)
  55. ↑ Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Janssens L, Andersen HR, Betriu A, Savonitto S, Adamus J, Peruga JZ, Kosmider M, Katz O, Neunteufl T, Jorgova J, Dorobantu M, Grinfeld L, Armstrong P, Brodie BR, Herrmann HC, Montalescot G, Neumann FJ, Effron MB, Barnathan ES, Topol EJ (2008). "Facilitated PCI in patients with ST-elevation myocardial infarction". The New England Journal of Medicine. 358 (21): 2205–17. doi:10.1056/NEJMoa0706816. PMID 18499565. Retrieved 2011-12-12. Unknown parameter |month= ignored (help)
  56. ↑ El Khoury C, Dubien PY, Mercier C, Belle L, Debaty G, Capel O, Perret T, Savary D, Serre P, Bonnefoy E (2010). "Prehospital high-dose tirofiban in patients undergoing primary percutaneous intervention. The AGIR-2 study". Archives of Cardiovascular Diseases. 103 (5): 285–92. doi:10.1016/j.acvd.2010.04.005. PMID 20619238. Retrieved 2011-12-12. Unknown parameter |month= ignored (help)
  57. ↑ Antoniucci D, Migliorini A, Parodi G, Valenti R, Rodriguez A, Hempel A, Memisha G, Santoro GM (2004). "Abciximab-supported infarct artery stent implantation for acute myocardial infarction and long-term survival: a prospective, multicenter, randomized trial comparing infarct artery stenting plus abciximab with stenting alone". Circulation. 109 (14): 1704–6. doi:10.1161/01.CIR.0000126284.40075.98. PMID 15066943. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
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  59. ↑ 59.0 59.1 Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Carroll JD, Rutherford BD, Lansky AJ (2002). "Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction". The New England Journal of Medicine. 346 (13): 957–66. doi:10.1056/NEJMoa013404. PMID 11919304. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
  60. ↑ 60.0 60.1 Montalescot G, Barragan P, Wittenberg O, Ecollan P, Elhadad S, Villain P, Boulenc JM, Morice MC, Maillard L, Pansiéri M, Choussat R, Pinton P (2001). "Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction". The New England Journal of Medicine. 344 (25): 1895–903. doi:10.1056/NEJM200106213442503. PMID 11419426. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
  61. ↑ 61.0 61.1 Mehilli J, Kastrati A, Schulz S, Früngel S, Nekolla SG, Moshage W, Dotzer F, Huber K, Pache J, Dirschinger J, Seyfarth M, Martinoff S, Schwaiger M, Schömig A (2009). "Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial". Circulation. 119 (14): 1933–40. doi:10.1161/CIRCULATIONAHA.108.818617. PMID 19332467. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
  62. ↑ De Luca G, Navarese E, Marino P (2009). "Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials". European Heart Journal. 30 (22): 2705–13. doi:10.1093/eurheartj/ehp118. PMC 2777025. PMID 19875386. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
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  64. ↑ Romagnoli E, Burzotta F, Trani C, Mazzari MA, Biondi-Zoccai GG, De Vita M, Giannico F, Niccoli G, Prati F, Rebuzzi AG, Mongiardo R, Crea F (2005). "Angiographic evaluation of the effect of intracoronary abciximab administration in patients undergoing urgent PCI". International Journal of Cardiology. 105 (3): 250–5. doi:10.1016/j.ijcard.2004.11.037. PMID 16274764. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
  65. ↑ Iversen A, Galatius S, Jensen JS (2008). "The Optimal Route of Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Abciximab During Percutaneous Coronary Intervention; Intravenous Versus Intracoronary". Current Cardiology Reviews. 4 (4): 293–9. doi:10.2174/157340308786349480. PMC 2801861. PMID 20066137. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
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  67. ↑ Kakkar AK, Moustapha A, Hanley HG, Weiss M, Caldito G, Misra P, Reddy PC, Tandon N (2004). "Comparison of intracoronary vs. intravenous administration of abciximab in coronary stenting". Catheterization and Cardiovascular Interventions :Official Journal of the Society for Cardiac Angiography & Interventions. 61 (1): 31–4. doi:10.1002/ccd.10730. PMID 14696156. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
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  69. ↑ Wöhrle J, Grebe OC, Nusser T, Al-Khayer E, Schaible S, Kochs M, Hombach V, Höher M (2003). "Reduction of major adverse cardiac events with intracoronary compared with intravenous bolus application of abciximab in patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty". Circulation. 107 (14): 1840–3. doi:10.1161/01.CIR.0000066852.98038.D1. PMID 12682003. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
  70. ↑ Deibele AJ, Kirtane AJ, Pinto DS, Lucca MJ, Neva C, Shui A, Murphy SA, Tcheng JE, Gibson CM (2006). "Intracoronary bolus administration of eptifibatide during percutaneous coronary stenting for non ST elevation myocardial infarction and unstable angina". Journal of Thrombosis and Thrombolysis. 22 (1): 47–50. doi:10.1007/s11239-006-7454-8. PMID 16786232. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
  71. ↑ Yang XC, Zhang DP, Wang LF, Xu L, Ge YG, Wang HS, Li WM, Ni ZH, Xia K, Lian Y, Xue YL, Ma LX (2007). "[Effects of intracoronary or intravenous tirofiban administration in patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention]". Zhonghua Xin Xue Guan Bing Za Zhi (in Chinese). 35 (6): 517–22. PMID 17711710. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  72. ↑ Hansen PR, Iversen A, Abdulla J (2010). "Improved clinical outcomes with intracoronary compared to intravenous abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a systematic review and meta-analysis". The Journal of Invasive Cardiology. 22 (6): 278–82. PMID 20516508. Retrieved 2011-12-14. Unknown parameter |month= ignored (help)
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  76. ↑ Akerblom A, James SK, Koutouzis M; et al. (2010). "Eptifibatide is noninferior to abciximab in primary percutaneous coronary intervention: results from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry)". J. Am. Coll. Cardiol. 56 (6): 470–5. doi:10.1016/j.jacc.2009.10.093. PMID 20670756. Unknown parameter |month= ignored (help)
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