ST elevation myocardial infarction fibrinolytic therapy: Difference between revisions

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{{Infobox_Disease |
  Name          = Myocardial infarction|
  Image          = |
  Caption        = |
  DiseasesDB    = 8664 |
  ICD10          = {{ICD10|I|21||i|20}}-{{ICD10|I|22||i|20}} |
  ICD9          = {{ICD9|410}} |
  ICDO          = |
  OMIM          = |
  MedlinePlus    = 000195 |
  eMedicineSubj  = |
  eMedicineTopic = |
  eMedicine_mult = |
  MeshID        = |
}}
'''For patient information click [[Heart attack (patient information)|here]]'''
{{SI}}
__NOTOC__
__NOTOC__
{{CMG}}
{{ST elevation myocardial infarction}}
 
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}
'''Associate Editor-In-Chief:''' {{CZ}}
 
{{Editor Join}}


==Overview==
==Overview==
Since the introduction of pharmacologic reperfusion therapy in the seventies, the main goal of reperfusion treatment has been to restore early, full and sustained patency of the infarct related artery <ref name="pmid10366375">{{cite journal |author=Gibson CM |title=Primary angioplasty compared with thrombolysis: new issues in the era of glycoprotein IIb/IIIa inhibition and intracoronary stenting |journal=Ann. Intern. Med. |volume=130 |issue=10 |pages=841–7 |year=1999 |month=May |pmid=10366375 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=10366375}}</ref>. In the seventies and in the eighties, [[fibrinolytic therapy]] was the primary reperfusion strategy that was available for the management of patients with acute ST elevation myocardial infarction (STEMI). An initial analysis consisting of 9 clinical trials by the Fibrinolysis Therapy Trialists (FTT) group demonstrated that there was a significant reduction in the mortality associated with the administration of [[fibrinolytic therapy]] compared to control subjects who did not receive fibrinolytic therapy (9.6% vs. 11.5%, p<0.00001) <ref name="pmid7905143">{{cite journal |author= |title=Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group |journal=Lancet |volume=343 |issue=8893 |pages=311–22 |year=1994 |month=February |pmid=7905143 |doi= |url=}}</ref>.
Since the introduction of pharmacologic reperfusion therapy in the seventies, the main goal of reperfusion treatment has been to restore early, full and sustained patency of the infarct related artery <ref name="pmid10366375">{{cite journal |author=Gibson CM |title=Primary angioplasty compared with thrombolysis: new issues in the era of glycoprotein IIb/IIIa inhibition and intracoronary stenting |journal=Ann. Intern. Med. |volume=130 |issue=10 |pages=841–7 |year=1999 |month=May |pmid=10366375 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=10366375}}</ref>. In the seventies and in the eighties, [[fibrinolytic therapy]] was the primary reperfusion strategy that was available for the management of patients with acute ST elevation myocardial infarction (STEMI). An initial analysis consisting of 9 clinical trials by the Fibrinolysis Therapy Trialists (FTT) group demonstrated that there was a significant reduction in the mortality associated with the administration of [[fibrinolytic therapy]] compared to control subjects who did not receive fibrinolytic therapy (9.6% vs. 11.5%, p<0.00001) <ref name="pmid7905143">{{cite journal |author= |title=Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group |journal=Lancet |volume=343 |issue=8893 |pages=311–22 |year=1994 |month=February |pmid=7905143 |doi= |url=}}</ref>.


==Mechanism of Benefit==
==Mechanism of Benefit==
View a clip from the late 70s heralding the advent of fibrinolytic therapy  
View a clip from the late 70s heralding the advent of fibrinolytic therapy  
{{#ev:youtube|B0gE7B-b_uw}}


<youtube v=B0gE7B-b_uw />
==Fibrinolytic Therapy==
 
==Fibrinolytic therapy==
 
{{Main|Thrombolysis}}
{{Main|Thrombolysis}}


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Depending on the thrombolytic agent being used, [[adjuvant]] anticoagulation with [[heparin]] or [[low molecular weight heparin]] may be of benefit.<ref name="GUSTO-1993-1">{{cite journal | author=The GUSTO investigators | title=An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. | journal=N Engl J Med | year=1993 | volume=329 | issue=10 | pages=673-82 | id=PMID 8204123}}</ref><ref name="Sabatine-2005">{{cite journal | author=Sabatine MS, Morrow DA, Montalescot G, Dellborg M, Leiva-Pons JL, Keltai M, Murphy SA, McCabe CH, Gibson CM, Cannon CP, Antman EM, Braunwald E; Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators. | title=Angiographic and clinical outcomes in patients receiving low-molecular-weight heparin versus unfractionated heparin in ST-elevation myocardial infarction treated with fibrinolytics in the CLARITY-TIMI 28 Trial. | journal=Circulation | year=2005 | volume=112 | issue=25 | pages=3846-54 | id=PMID 16291601}}</ref> With tPA and related agents (reteplase and tenecteplase), heparin is needed to maintain coronary artery patency. Because of the anticoagulant effect of fibrinogen depletion with streptokinase<ref name="Cowley-1983">{{cite journal | author=Cowley MJ, Hastillo A, Vetrovec GW, Fisher LM, Garrett R, Hess ML. | title=Fibrinolytic effects of intracoronary streptokinase administration in patients with acute myocardial infarction and coronary insufficiency. | journal=Circulation | year=1983 | volume=67 | issue=5 | pages=1031-8 | id=PMID 6831667}}</ref> and urokinase<ref name="Lourenco-1989">{{cite journal | author=Lourenco DM, Dosne AM, Kher A, Samama M. | title=Effect of standard heparin and a low molecular weight heparin on thrombolytic and fibrinolytic activity of single-chain urokinase plasminogen activator ''in vitro''. | journal=Thromb Haemost | year=1989 | volume=62 | issue=3 | pages=923-6 | id=PMID 2556812}}</ref><ref name="Van de Werf-1986">{{cite journal | author=Van de Werf F, Vanhaecke J, de Geest H, Verstraete M, Collen D. | title=Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction. | journal=Circulation | year=1986 | volume=74 | issue=5 | pages=1066-70 | id=PMID 2429783}}</ref><ref name="Bode-1988">{{cite journal | author=Bode C, Schoenermark S, Schuler G, Zimmermann R, Schwarz F, Kuebler W. | title=Efficacy of intravenous prourokinase and a combination of prourokinase and urokinase in acute myocardial infarction. | journal=Am J Cardiol | year=1988 | volume=61 | issue=13 | pages=971-4 | id=PMID 2452564}}</ref> treatment, it is less necessary there.<ref name="GUSTO-1993-1"/>
Depending on the thrombolytic agent being used, [[adjuvant]] anticoagulation with [[heparin]] or [[low molecular weight heparin]] may be of benefit.<ref name="GUSTO-1993-1">{{cite journal | author=The GUSTO investigators | title=An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. | journal=N Engl J Med | year=1993 | volume=329 | issue=10 | pages=673-82 | id=PMID 8204123}}</ref><ref name="Sabatine-2005">{{cite journal | author=Sabatine MS, Morrow DA, Montalescot G, Dellborg M, Leiva-Pons JL, Keltai M, Murphy SA, McCabe CH, Gibson CM, Cannon CP, Antman EM, Braunwald E; Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators. | title=Angiographic and clinical outcomes in patients receiving low-molecular-weight heparin versus unfractionated heparin in ST-elevation myocardial infarction treated with fibrinolytics in the CLARITY-TIMI 28 Trial. | journal=Circulation | year=2005 | volume=112 | issue=25 | pages=3846-54 | id=PMID 16291601}}</ref> With tPA and related agents (reteplase and tenecteplase), heparin is needed to maintain coronary artery patency. Because of the anticoagulant effect of fibrinogen depletion with streptokinase<ref name="Cowley-1983">{{cite journal | author=Cowley MJ, Hastillo A, Vetrovec GW, Fisher LM, Garrett R, Hess ML. | title=Fibrinolytic effects of intracoronary streptokinase administration in patients with acute myocardial infarction and coronary insufficiency. | journal=Circulation | year=1983 | volume=67 | issue=5 | pages=1031-8 | id=PMID 6831667}}</ref> and urokinase<ref name="Lourenco-1989">{{cite journal | author=Lourenco DM, Dosne AM, Kher A, Samama M. | title=Effect of standard heparin and a low molecular weight heparin on thrombolytic and fibrinolytic activity of single-chain urokinase plasminogen activator ''in vitro''. | journal=Thromb Haemost | year=1989 | volume=62 | issue=3 | pages=923-6 | id=PMID 2556812}}</ref><ref name="Van de Werf-1986">{{cite journal | author=Van de Werf F, Vanhaecke J, de Geest H, Verstraete M, Collen D. | title=Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction. | journal=Circulation | year=1986 | volume=74 | issue=5 | pages=1066-70 | id=PMID 2429783}}</ref><ref name="Bode-1988">{{cite journal | author=Bode C, Schoenermark S, Schuler G, Zimmermann R, Schwarz F, Kuebler W. | title=Efficacy of intravenous prourokinase and a combination of prourokinase and urokinase in acute myocardial infarction. | journal=Am J Cardiol | year=1988 | volume=61 | issue=13 | pages=971-4 | id=PMID 2452564}}</ref> treatment, it is less necessary there.<ref name="GUSTO-1993-1"/>
==Clinical Trial Data==


==Side Effects==
==Side Effects==
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In cases of failure of the thrombolytic agent to open the infarct-related coronary artery, the patient is then either treated conservatively with anticoagulants and allowed to "complete the infarction" or [[percutaneous coronary intervention]] (PCI, see below) is then performed.  Percutaneous coronary intervention in this setting is known as "rescue PCI" or "salvage PCI". Complications, particularly bleeding, are significantly higher with rescue PCI than with primary PCI due to the action of the thrombolytic agent.
In cases of failure of the thrombolytic agent to open the infarct-related coronary artery, the patient is then either treated conservatively with anticoagulants and allowed to "complete the infarction" or [[percutaneous coronary intervention]] (PCI, see below) is then performed.  Percutaneous coronary intervention in this setting is known as "rescue PCI" or "salvage PCI". Complications, particularly bleeding, are significantly higher with rescue PCI than with primary PCI due to the action of the thrombolytic agent.


==See also==
==2013 Revised and 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (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="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>==
* [[acute coronary syndrome]]
* [[angina pectoris|angina]]
* [[Cardiac arrest]]
* [[coronary thrombosis]]
* [[Hibernating myocardium]]
* [[Stunned myocardium]]
* [[Ventricular remodeling]]


==External links==
===Indications for Fibrinolytic Therapy (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="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>===
* [http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=pub Risk Assessment Tool for Estimating Your 10-year Risk of Having a Heart Attack] - based on information of the [[Framingham Heart Study]], from the United States [[National Heart, Lung and Blood Institute]]
* [http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Attack] - overview of resources from [[MedlinePlus]].
* [http://ww2.heartandstroke.ca/Page.asp?PageID=1975&ArticleID=5288 Heart Attack Warning Signals] from the Heart and Stroke Foundation of Canada
* [http://www.regionalpci-stemi.org/index.html Regional PCI for STEMI Resource Center] - Evidence based online resource center for the development of regional PCI networks for acute STEMI
* [http://www.stemisystems.org/ STEMI Systems] - Articles, profiles, and reviews of the latest publications involved in STEMI care. Quarterly newsletter.
* [http://d2b.acc.org/ American College of Cardiology (ACC) Door to Balloon (D2B) Initiative.]
* [http://www.americanheart.org/heartattack American Heart Association's Heart Attack web site] - Information and resources for preventing, recognizing and treating heart attack.


==ACC / AHA Guidelines- Indications for Fibrinolytic Therapy (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>==
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In the absence of contraindications, [[fibrinolytic therapy]] should be administered to [[STEMI]] patients with symptom onset within the prior 12 hours and ST elevation greater than 0.1 mV in at least 2 contiguous [[precordial]] leads or at least 2 adjacent limb leads. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' In the absence of contraindications, fibrinolytic therapy should be administered to [[STEMI]] patients with symptom onset within the prior 12 hours and new or presumably new LBBB. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' In the absence of contraindications, fibrinolytic therapy should be administered to patients with STEMI at non–PCI-capable hospitals when the anticipated FMC-to-device time at a PCI-capable hospital exceeds 120 minutes because of unavoidable delays.<ref name="pmid7905143">{{cite journal |author= |title=Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group |journal=Lancet |volume=343 |issue=8893 |pages=311–22 |year=1994 |month=February |pmid=7905143 |doi= |url=}}</ref><ref name="pmid14516884">{{cite journal |author=Nallamothu BK, Bates ER |title=Percutaneous coronary intervention versus fibrinolytic therapy in acute myocardial infarction: is timing (almost) everything? |journal=Am. J. Cardiol. |volume=92 |issue=7 |pages=824–6 |year=2003 |month=October |pmid=14516884 |doi= |url=}}</ref><ref name="pmid17075010">{{cite journal |author=Pinto DS, Kirtane AJ, Nallamothu BK, ''et al.'' |title=Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reperfusion strategy |journal=Circulation |volume=114 |issue=19 |pages=2019–25 |year=2006 |month=November |pmid=17075010 |doi=10.1161/CIRCULATIONAHA.106.638353 |url=}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' When fibrinolytic therapy is indicated or chosen as the primary reperfusion strategy, it should be administered within 30 minutes of hospital arrival.<ref name="pmid8813982">{{cite journal |author=Boersma E, Maas AC, Deckers JW, Simoons ML |title=Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour |journal=Lancet |volume=348 |issue=9030 |pages=771–5 |year=1996 |month=September |pmid=8813982 |doi=10.1016/S0140-6736(96)02514-7 |url=}}</ref><ref name="pmid10908248">{{cite journal |author=Chareonthaitawee P, Gibbons RJ, Roberts RS, Christian TF, Burns R, Yusuf S |title=The impact of time to thrombolytic treatment on outcome in patients with acute myocardial infarction. For the CORE investigators (Collaborative Organisation for RheothRx Evaluation) |journal=Heart |volume=84 |issue=2 |pages=142–8 |year=2000 |month=August |pmid=10908248 |pmc=1760917 |doi= |url=}}</ref><ref name="pmid17920362">{{cite journal |author=McNamara RL, Herrin J, Wang Y, ''et al.'' |title=Impact of delay in door-to-needle time on mortality in patients with ST-segment elevation myocardial infarction |journal=Am. J. Cardiol. |volume=100 |issue=8 |pages=1227–32 |year=2007 |month=October |pmid=17920362 |pmc=2715362 |doi=10.1016/j.amjcard.2007.05.043 |url=}}</ref><ref name="pmid9581715">{{cite journal |author=Milavetz JJ, Giebel DW, Christian TF, Schwartz RS, Holmes DR, Gibbons RJ |title=Time to therapy and salvage in myocardial infarction |journal=J. Am. Coll. Cardiol. |volume=31 |issue=6 |pages=1246–51 |year=1998 |month=May |pmid=9581715 |doi= |url=}}</ref><ref name="pmid8636549">{{cite journal |author=Newby LK, Rutsch WR, Califf RM, ''et al.'' |title=Time from symptom onset to treatment and outcomes after thrombolytic therapy. GUSTO-1 Investigators |journal=J. Am. Coll. Cardiol. |volume=27 |issue=7 |pages=1646–55 |year=1996 |month=June |pmid=8636549 |doi= |url=}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' In the absence of contraindications, fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours when it is anticipated that primary PCI cannot be performed within 120 minutes of FMC. <ref name="pmid7905143">{{cite journal |author= |title=Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group |journal=Lancet |volume=343 |issue=8893 |pages=311–22 |year=1994 |month=February |pmid=7905143 |doi= |url=}}</ref><ref name="pmid2894490">{{cite journal |author= |title=Effect of intravenous APSAC on mortality after acute myocardial infarction: preliminary report of a placebo-controlled clinical trial. AIMS Trial Study Group |journal=Lancet |volume=1 |issue=8585 |pages=545–9 |year=1988 |month=March |pmid=2894490 |doi= |url=}}</ref><ref name="pmid8103875">{{cite journal |author= |title=Randomised trial of late thrombolysis in patients with suspected acute myocardial infarction. EMERAS (Estudio Multicéntrico Estreptoquinasa Repúblicas de América del Sur) Collaborative Group |journal=Lancet |volume=342 |issue=8874 |pages=767–72 |year=1993 |month=September |pmid=8103875 |doi= |url=}}</ref><ref name="pmid8103875">{{cite journal |author= |title=Randomised trial of late thrombolysis in patients with suspected acute myocardial infarction. EMERAS (Estudio Multicéntrico Estreptoquinasa Repúblicas de América del Sur) Collaborative Group |journal=Lancet |volume=342 |issue=8874 |pages=767–72 |year=1993 |month=September |pmid=8103875 |doi= |url=}}</ref><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=}}</ref><ref name="pmid8103874">{{cite journal |author= |title=Late Assessment of Thrombolytic Efficacy (LATE) study with alteplase 6-24 hours after onset of acute myocardial infarction |journal=Lancet |volume=342 |issue=8874 |pages=759–66 |year=1993 |month=September |pmid=8103874 |doi= |url=}}</ref><ref name="pmid1877476">{{cite journal |author=Rossi P, Bolognese L |title=Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group |journal=Am. J. Cardiol. |volume=68 |issue=6 |pages=585–92 |year=1991 |month=September |pmid=1877476 |doi= |url=}}</ref><ref name="pmid2871492">{{cite journal |author= |title=A prospective trial of intravenous streptokinase in acute myocardial infarction (I.S.A.M.). Mortality, morbidity, and infarct size at 21 days. The I.S.A.M. Study Group |journal=N. Engl. J. Med. |volume=314 |issue=23 |pages=1465–71 |year=1986 |month=June |pmid=2871492 |doi=10.1056/NEJM198606053142301 |url=}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}


{{cquote|
{|class="wikitable"
===Class I===
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (Harm)
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' [[Fibrinolytic therapy]] should not be administered to asymptomatic patients whose initial symptoms of [[STEMI]]began more than 24 hours earlier. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''2.''' Fibrinolytic therapy should not be administered to patients whose [[12-lead ECG]] shows only [[ST-segment depression]] except if a [[true posterior MI]] is suspected. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''3.''' Fibrinolytic therapy should not be administered to patients with ST depression except when a true posterior (inferobasal) MI is suspected or when associated with ST elevation in lead aVR.<ref name="pmid7905143">{{cite journal |author= |title=Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group |journal=Lancet |volume=343 |issue=8893 |pages=311–22 |year=1994 |month=February |pmid=7905143 |doi= |url=}}</ref><ref name="pmid18987380">{{cite journal |author=de Winter RJ, Verouden NJ, Wellens HJ, Wilde AA |title=A new ECG sign of proximal LAD occlusion |journal=N. Engl. J. Med. |volume=359 |issue=19 |pages=2071–3 |year=2008 |month=November |pmid=18987380 |doi=10.1056/NEJMc0804737 |url=}}</ref><ref name="pmid8419023">{{cite journal |author= |title=Early effects of tissue-type plasminogen activator added to conventional therapy on the culprit coronary lesion in patients presenting with ischemic cardiac pain at rest. Results of the Thrombolysis in Myocardial Ischemia (TIMI IIIA) Trial |journal=Circulation |volume=87 |issue=1 |pages=38–52 |year=1993 |month=January |pmid=8419023 |doi= |url=}}</ref><ref name="pmid12885742">{{cite journal |author=Barrabés JA, Figueras J, Moure C, Cortadellas J, Soler-Soler J |title=Prognostic value of lead aVR in patients with a first non-ST-segment elevation acute myocardial infarction |journal=Circulation |volume=108 |issue=7 |pages=814–9 |year=2003 |month=August |pmid=12885742 |doi=10.1161/01.CIR.0000084553.92734.83 |url=}}</ref><ref name="pmid16479036">{{cite journal |author=Jong GP, Ma T, Chou P, Shyu MY, Tseng WK, Chang TC |title=Reciprocal changes in 12-lead electrocardiography can predict left main coronary artery lesion in patients with acute myocardial infarction |journal=Int Heart J |volume=47 |issue=1 |pages=13–20 |year=2006 |month=January |pmid=16479036 |doi= |url=}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


1. In the absence of contraindications, [[fibrinolytic therapy]] should be administered to [[STEMI]] patients with symptom onset within the prior 12 hours and ST elevation greater than 0.1 mV in at least 2 contiguous precordial leads or at least 2 adjacent limb leads. ''(Level of Evidence: A)''
{|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 the absence of contraindications, it is reasonable to administer [[fibrinolytic therapy]] to [[STEMI]] patients with symptom onset within the prior 12 hours and [[12-lead ECG]] findings consistent with a [[true posterior MI]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In the absence of contraindications, it is reasonable to administer fibrinolytic therapy to patients with symptoms of [[STEMI]] beginning within the prior 12 to 24 hours who have continuing [[ischemic symptoms]] and ST elevation greater than 0.1 mV in at least 2 contiguous precordial leads or at least 2 adjacent limb leads. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In the absence of contraindications and when PCI is not available, fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or electrocardiographic evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability.''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}


2. In the absence of contraindications, [[fibrinolytic therapy]] should be administered to [[STEMI]] patients with symptom onset within the prior 12 hours and new or presumably new LBBB. ''(Level of Evidence: A)''
===Adjunctive Antiplatelet Therapy with Fibrinolysis (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>===


===Class IIa===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Aspirin (162- to 325-mg loading dose) and clopidogrel (300-mg loading dose for patients <75 years of age, 75-mg dose for patients >75 years of age) should be administered to patients with STEMI who receive fibrinolytic therapy.<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=}}</ref><ref name="pmid16271642">{{cite journal |author=Chen ZM, Jiang LX, Chen YP, ''et al.'' |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=}}</ref><ref name="pmid15758000">{{cite journal |author=Sabatine MS, Cannon CP, Gibson CM, ''et al.'' |title=Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation |journal=N. Engl. J. Med. |volume=352 |issue=12 |pages=1179–89 |year=2005 |month=March |pmid=15758000 |doi=10.1056/NEJMoa050522 |url=}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Aspirin should be continued indefinitely <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=}}</ref><ref name="pmid16271642">{{cite journal |author=Chen ZM, Jiang LX, Chen YP, ''et al.'' |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=}}</ref><ref name="pmid15758000">{{cite journal |author=Sabatine MS, Cannon CP, Gibson CM, ''et al.'' |title=Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation |journal=N. Engl. J. Med. |volume=352 |issue=12 |pages=1179–89 |year=2005 |month=March |pmid=15758000 |doi=10.1056/NEJMoa050522 |url=}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' and clopidogrel (75 mg daily) should be continued for at least 14 days <ref name="pmid16271642">{{cite journal |author=Chen ZM, Jiang LX, Chen YP, ''et al.'' |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=}}</ref><ref name="pmid15758000">{{cite journal |author=Sabatine MS, Cannon CP, Gibson CM, ''et al.'' |title=Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation |journal=N. Engl. J. Med. |volume=352 |issue=12 |pages=1179–89 |year=2005 |month=March |pmid=15758000 |doi=10.1056/NEJMoa050522 |url=}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''and up to 1 year ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' in patients with STEMI who receive fibrinolytic therapy.<nowiki>"</nowiki>
|}


1. In the absence of contraindications, it is reasonable to administer [[fibrinolytic therapy]] to [[STEMI]] patients with symptom onset within the prior 12 hours and [[12-lead ECG]] findings consistent with a [[true posterior MI]]. ''(Level of Evidence: C)''
{|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 use aspirin 81 mg per day in preference to higher maintenance doses after fibrinolytic therapy.<ref name="pmid11786451">{{cite journal |author= |title=Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients |journal=BMJ |volume=324 |issue=7329 |pages=71–86 |year=2002 |month=January |pmid=11786451 |pmc=64503 |doi= |url=}}</ref><ref name="pmid22052934">{{cite journal |author=Smith SC, Benjamin EJ, Bonow RO, ''et al.'' |title=AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation |journal=Circulation |volume=124 |issue=22 |pages=2458–73 |year=2011 |month=November |pmid=22052934 |doi=10.1161/CIR.0b013e318235eb4d |url=}}</ref><ref name="pmid15877994">{{cite journal |author=Serebruany VL, Steinhubl SR, Berger PB, ''et al.'' |title=Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials |journal=Am. J. Cardiol. |volume=95 |issue=10 |pages=1218–22 |year=2005 |month=May |pmid=15877994 |doi=10.1016/j.amjcard.2005.01.049 |url=}}</ref><ref name="pmid19293071">{{cite journal |author=Steinhubl SR, Bhatt DL, Brennan DM, ''et al.'' |title=Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding |journal=Ann. Intern. Med. |volume=150 |issue=6 |pages=379–86 |year=2009 |month=March |pmid=19293071 |doi= |url=}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}


2. In the absence of contraindications, it is reasonable to administer [[fibrinolytic therapy]] to patients with symptoms of [[STEMI]] beginning within the prior 12 to 24 hours who have continuing [[ischemic symptoms]] and ST elevation greater than 0.1 mV in at least 2 contiguous precordial leads or at least 2 adjacent limb leads. ''(Level of Evidence: B)''
===Contraindications / Cautions to Fibrinolytic Therapy (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>===


===Class III===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Healthcare providers should ascertain whether the patient has neurological contraindications to fibrinolytic therapy, including: any history of [[intracranial hemorrhage]] or significant closed head or [[facial trauma]] within the past 3 months, uncontrolled [[hypertension]], or [[ischemic stroke]] within the past 3 months.  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' [[STEMI]] patients at substantial (greater than or equal to 4%) risk of [[ICH]] should be treated with [[PCI]] rather than with [[fibrinolytic therapy]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}


1. [[Fibrinolytic therapy]] should not be administered to asymptomatic patients whose initial symptoms of [[STEMI]] began more than 24 hours earlier. ''(Level of Evidence: C)''
===Complications of Fibrinolytic Therapy (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>===


2. [[Fibrinolytic therapy]] should not be administered to patients whose [[12-lead ECG]] shows only [[ST-segment depression]] except if a [[true posterior MI]] is suspected. ''(Level of Evidence: A)''}}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' The occurrence of a change in neurological status during or after [[reperfusion therapy]], particularly within the first 24 hours after initiation of treatment, is considered to be due to [[ICH]] until proven otherwise. [[Fibrinolytic]], [[antiplatelet]], and [[anticoagulant]] therapies should be discontinued until [[brain]] imaging scan shows no evidence of [[ICH]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' [[Neurology]] and/or [[neurosurgery]] or [[hematology]] consultations should be obtained for [[STEMI]] patients who have [[ICH]], as dictated by clinical circumstances. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' In patients with [[ICH]], infusions of [[cryoprecipitate]], fresh frozen [[plasma]], [[protamine]], and [[platelet]]s should be given, as dictated by clinical circumstances. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}


==ACC / AHA Guidelines- Contraindications / Cautions to Fibrinolytic Therapy (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>==
{|class="wikitable"
{{cquote| 
|-
===Class I===
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
 
|-
1. Healthcare providers should ascertain whether the patient has neurological contraindications to [[fibrinolytic therapy]], including: any history of [[intracranial hemorrhage]] or significant closed head or [[facial trauma]] within the past 3 months, uncontrolled [[hypertension]], or [[ischemic stroke]] within the past 3 months. ''(Level of Evidence: A)''
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with [[ICH]] it is reasonable to: '' <nowiki>"</nowiki>
 
|-
2. [[STEMI]] patients at substantial (greater than or equal to 4%) risk of [[ICH]] should be treated with [[PCI]] rather than with [[fibrinolytic therapy]]. ''(Level of Evidence: A)''}}
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''a.''' Optimize [[blood pressure]] and [[blood glucose]] levels. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
 
|-
==ACC / AHA Guidelines- Complications of Fibrinolytic Therapy (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>==
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''b.''' Reduce [[intracranial pressure]] with an infusion of [[mannitol]], [[endotracheal intubation]], and [[hyperventilation]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
 
|-
{{cquote| 
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''c.''' Consider neurosurgical evacuation of [[ICH]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
===Class I===
|}
1. The occurrence of a change in neurological status during or after [[reperfusion therapy]], particularly within the first 24 hours after initiation of treatment, is considered to be due to [[ICH]] until proven otherwise. [[Fibrinolytic]], [[antiplatelet]], and [[anticoagulant]] therapies should be discontinued until [[brain]] imaging scan shows no evidence of [[ICH]]. ''(Level of Evidence: A)''
 
2. [[Neurology]] and/or [[neurosurgery]] or [[hematology]] consultations should be obtained for [[STEMI]] patients who have [[ICH]], as dictated by clinical circumstances. ''(Level of Evidence: C)''
 
3. In patients with [[ICH]], infusions of [[cryoprecipitate]], fresh frozen [[plasma]], [[protamine]], and [[platelet]]s should be given, as dictated by clinical circumstances. ''(Level of Evidence: C)''
 
===Class IIa===
 
1. In patients with [[ICH]] it is reasonable to:
 
a. Optimize [[blood pressure]] and [[blood glucose]] levels ''(Level of Evidence: C)''
 
b. Reduce [[intracranial pressure]] with an infusion of [[mannitol]], [[endotracheal intubation]], and [[hyperventilation]] ''(Level of Evidence: C)''
 
c. Consider neurosurgical evacuation of [[ICH]] ''(Level of Evidence: C)}}''


==Sources==
==Sources==
Line 127: Line 129:


*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>
*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 17:20, 7 November 2016

Acute Coronary Syndrome Main Page

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ST elevation myocardial infarction fibrinolytic therapy On the Web

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

Since the introduction of pharmacologic reperfusion therapy in the seventies, the main goal of reperfusion treatment has been to restore early, full and sustained patency of the infarct related artery [1]. In the seventies and in the eighties, fibrinolytic therapy was the primary reperfusion strategy that was available for the management of patients with acute ST elevation myocardial infarction (STEMI). An initial analysis consisting of 9 clinical trials by the Fibrinolysis Therapy Trialists (FTT) group demonstrated that there was a significant reduction in the mortality associated with the administration of fibrinolytic therapy compared to control subjects who did not receive fibrinolytic therapy (9.6% vs. 11.5%, p<0.00001) [2].

Mechanism of Benefit

View a clip from the late 70s heralding the advent of fibrinolytic therapy {{#ev:youtube|B0gE7B-b_uw}}

Fibrinolytic Therapy

Main article: Thrombolysis

Thrombolytic therapy is indicated for the treatment of STEMI if the drug can be administered within 12 hours of the onset of symptoms, the patient is eligible based on exclusion criteria, and primary PCI is not immediately available.[3] The effectiveness of thrombolytic therapy is highest in the first 2 hours. After 12 hours, the risk associated with thrombolytic therapy outweighs any benefit.[2][4] Because irreversible injury occurs within 2–4 hours of the infarction, there is a limited window of time available for reperfusion to work.

Thrombolytic drugs are contraindicated for the treatment of unstable angina and NSTEMI[5] and for the treatment of individuals with evidence of cardiogenic shock.[6]

Although no perfect thrombolytic agent exists, an ideal thrombolytic drug would lead to rapid reperfusion, have a high sustained patency rate, be specific for recent thrombi, be easily and rapidly administered, create a low risk for intra-cerebral and systemic bleeding, have no antigenicity, adverse hemodynamic effects, or clinically significant drug interactions, and be cost effective.[7] Currently available thrombolytic agents include streptokinase, urokinase, and alteplase (recombinant tissue plasminogen activator, rtPA). More recently, thrombolytic agents similar in structure to rtPA such as reteplase and tenecteplase have been used. These newer agents boast efficacy at least as good as rtPA with significantly easier administration. The thrombolytic agent used in a particular individual is based on institution preference and the age of the patient.

Depending on the thrombolytic agent being used, adjuvant anticoagulation with heparin or low molecular weight heparin may be of benefit.[8][9] With tPA and related agents (reteplase and tenecteplase), heparin is needed to maintain coronary artery patency. Because of the anticoagulant effect of fibrinogen depletion with streptokinase[10] and urokinase[11][12][13] treatment, it is less necessary there.[8]

Side Effects

Intracranial bleeding (ICB) and subsequent cerebrovascular accident (CVA) is a serious side effect of thrombolytic use. The risk of ICB is dependent on a number of factors, including a previous episode of intracranial bleed, age of the individual, and the thrombolytic regimen that is being used. In general, the risk of ICB due to thrombolytic use for the treatment of an acute myocardial infarction is between 0.5 and 1 percent.[8]

Thrombolytic therapy to abort a myocardial infarction is not always effective. The degree of effectiveness of a thrombolytic agent is dependent on the time since the myocardial infarction began, with the best results occurring if the thrombolytic agent is used within two hours of the onset of symptoms.[14] If the individual presents more than 12 hours after symptoms commenced, the risk of intracranial bleed are considered higher than the benefits of the thrombolytic agent.[15] Failure rates of thrombolytics can be as high as 20% or higher.[16]

In cases of failure of the thrombolytic agent to open the infarct-related coronary artery, the patient is then either treated conservatively with anticoagulants and allowed to "complete the infarction" or percutaneous coronary intervention (PCI, see below) is then performed. Percutaneous coronary intervention in this setting is known as "rescue PCI" or "salvage PCI". Complications, particularly bleeding, are significantly higher with rescue PCI than with primary PCI due to the action of the thrombolytic agent.

2013 Revised and 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (DO NOT EDIT)[17][3]

Indications for Fibrinolytic Therapy (DO NOT EDIT)[17][3]

Class I
"1. In the absence of contraindications, fibrinolytic therapy should be administered to STEMI patients with symptom onset within the prior 12 hours and ST elevation greater than 0.1 mV in at least 2 contiguous precordial leads or at least 2 adjacent limb leads. (Level of Evidence: A)"
"2. In the absence of contraindications, fibrinolytic therapy should be administered to STEMI patients with symptom onset within the prior 12 hours and new or presumably new LBBB. (Level of Evidence: A) "
"3. In the absence of contraindications, fibrinolytic therapy should be administered to patients with STEMI at non–PCI-capable hospitals when the anticipated FMC-to-device time at a PCI-capable hospital exceeds 120 minutes because of unavoidable delays.[2][18][19] (Level of Evidence: B)"
"4. When fibrinolytic therapy is indicated or chosen as the primary reperfusion strategy, it should be administered within 30 minutes of hospital arrival.[4][20][21][22][23] (Level of Evidence: B)"
"5. In the absence of contraindications, fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours when it is anticipated that primary PCI cannot be performed within 120 minutes of FMC. [2][24][25][25][26][27][28][29](Level of Evidence: A)"
Class III (Harm)
"1. Fibrinolytic therapy should not be administered to asymptomatic patients whose initial symptoms of STEMIbegan more than 24 hours earlier. (Level of Evidence: C)"
"2. Fibrinolytic therapy should not be administered to patients whose 12-lead ECG shows only ST-segment depression except if a true posterior MI is suspected. (Level of Evidence: A)"
"3. Fibrinolytic therapy should not be administered to patients with ST depression except when a true posterior (inferobasal) MI is suspected or when associated with ST elevation in lead aVR.[2][30][31][32][33](Level of Evidence: B)"
Class IIa
"1. In the absence of contraindications, it is reasonable to administer fibrinolytic therapy to STEMI patients with symptom onset within the prior 12 hours and 12-lead ECG findings consistent with a true posterior MI. (Level of Evidence: C)"
"2. In the absence of contraindications, it is reasonable to administer fibrinolytic therapy to patients with symptoms of STEMI beginning within the prior 12 to 24 hours who have continuing ischemic symptoms and ST elevation greater than 0.1 mV in at least 2 contiguous precordial leads or at least 2 adjacent limb leads. (Level of Evidence: B)"
"3. In the absence of contraindications and when PCI is not available, fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or electrocardiographic evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability.(Level of Evidence: C)"

Adjunctive Antiplatelet Therapy with Fibrinolysis (DO NOT EDIT)[17]

Class I
"1. Aspirin (162- to 325-mg loading dose) and clopidogrel (300-mg loading dose for patients <75 years of age, 75-mg dose for patients >75 years of age) should be administered to patients with STEMI who receive fibrinolytic therapy.[26][34][35](Level of Evidence: A) "
"2. Aspirin should be continued indefinitely [26][34][35](Level of Evidence: A) and clopidogrel (75 mg daily) should be continued for at least 14 days [34][35](Level of Evidence: A)and up to 1 year (Level of Evidence: C) in patients with STEMI who receive fibrinolytic therapy."
Class IIa
"1. It is reasonable to use aspirin 81 mg per day in preference to higher maintenance doses after fibrinolytic therapy.[36][37][38][39](Level of Evidence: B) "

Contraindications / Cautions to Fibrinolytic Therapy (DO NOT EDIT)[3]

Class I
"1. Healthcare providers should ascertain whether the patient has neurological contraindications to fibrinolytic therapy, including: any history of intracranial hemorrhage or significant closed head or facial trauma within the past 3 months, uncontrolled hypertension, or ischemic stroke within the past 3 months. (Level of Evidence: A)"
"2. STEMI patients at substantial (greater than or equal to 4%) risk of ICH should be treated with PCI rather than with fibrinolytic therapy. (Level of Evidence: A)"

Complications of Fibrinolytic Therapy (DO NOT EDIT)[3]

Class I
"1. The occurrence of a change in neurological status during or after reperfusion therapy, particularly within the first 24 hours after initiation of treatment, is considered to be due to ICH until proven otherwise. Fibrinolytic, antiplatelet, and anticoagulant therapies should be discontinued until brain imaging scan shows no evidence of ICH. (Level of Evidence: A)"
"2. Neurology and/or neurosurgery or hematology consultations should be obtained for STEMI patients who have ICH, as dictated by clinical circumstances. (Level of Evidence: A)"
"3. In patients with ICH, infusions of cryoprecipitate, fresh frozen plasma, protamine, and platelets should be given, as dictated by clinical circumstances. (Level of Evidence: A)"
Class IIa
"1. In patients with ICH it is reasonable to: "
"a. Optimize blood pressure and blood glucose levels. (Level of Evidence: C)"
"b. Reduce intracranial pressure with an infusion of mannitol, endotracheal intubation, and hyperventilation. (Level of Evidence: C)"
"c. Consider neurosurgical evacuation of ICH. (Level of Evidence: C)"

Sources

  • The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction [40]
  • The 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction [41]
  • 2013 Revised ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction[17]

References

  1. ↑ Gibson CM (1999). "Primary angioplasty compared with thrombolysis: new issues in the era of glycoprotein IIb/IIIa inhibition and intracoronary stenting". Ann. Intern. Med. 130 (10): 841–7. PMID 10366375. Unknown parameter |month= ignored (help)
  2. ↑ 2.0 2.1 2.2 2.3 2.4 "Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group". Lancet. 343 (8893): 311–22. 1994. PMID 7905143. Unknown parameter |month= ignored (help)
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Antman EM, Anbe DT, Armstrong PW; et al. (2004). "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)". Circulation. 110 (5): 588–636. doi:10.1161/01.CIR.0000134791.68010.FA. PMID 15289388. Unknown parameter |month= ignored (help)
  4. ↑ 4.0 4.1 Boersma E, Maas AC, Deckers JW, Simoons ML (1996). "Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour". Lancet. 348 (9030): 771–5. doi:10.1016/S0140-6736(96)02514-7. PMID 8813982. Unknown parameter |month= ignored (help)
  5. ↑ "Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia". Circulation. 89 (4): 1545–56. 1994. PMID 8149520. Unknown parameter |month= ignored (help)
  6. ↑ Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley JD, Buller CE, Jacobs AK, Slater JN, Col J, McKinlay SM, LeJemtel TH. (1999). "Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock". N Engl J Med. 341 (9): 625–34. PMID 10460813.
  7. ↑ White HD, Van de Werf FJ (1998). "Thrombolysis for acute myocardial infarction". Circulation. 97 (16): 1632–46. PMID 9593569. Unknown parameter |month= ignored (help)
  8. ↑ 8.0 8.1 8.2 The GUSTO investigators (1993). "An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators". N Engl J Med. 329 (10): 673–82. PMID 8204123.
  9. ↑ Sabatine MS, Morrow DA, Montalescot G, Dellborg M, Leiva-Pons JL, Keltai M, Murphy SA, McCabe CH, Gibson CM, Cannon CP, Antman EM, Braunwald E; Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators. (2005). "Angiographic and clinical outcomes in patients receiving low-molecular-weight heparin versus unfractionated heparin in ST-elevation myocardial infarction treated with fibrinolytics in the CLARITY-TIMI 28 Trial". Circulation. 112 (25): 3846–54. PMID 16291601.
  10. ↑ Cowley MJ, Hastillo A, Vetrovec GW, Fisher LM, Garrett R, Hess ML. (1983). "Fibrinolytic effects of intracoronary streptokinase administration in patients with acute myocardial infarction and coronary insufficiency". Circulation. 67 (5): 1031–8. PMID 6831667.
  11. ↑ Lourenco DM, Dosne AM, Kher A, Samama M. (1989). "Effect of standard heparin and a low molecular weight heparin on thrombolytic and fibrinolytic activity of single-chain urokinase plasminogen activator in vitro". Thromb Haemost. 62 (3): 923–6. PMID 2556812.
  12. ↑ Van de Werf F, Vanhaecke J, de Geest H, Verstraete M, Collen D. (1986). "Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction". Circulation. 74 (5): 1066–70. PMID 2429783.
  13. ↑ Bode C, Schoenermark S, Schuler G, Zimmermann R, Schwarz F, Kuebler W. (1988). "Efficacy of intravenous prourokinase and a combination of prourokinase and urokinase in acute myocardial infarction". Am J Cardiol. 61 (13): 971–4. PMID 2452564.
  14. ↑ Boersma E, Maas AC, Deckers JW, Simoons ML. (1996). "Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour". Lancet. 348 (9030): 771–5. PMID 8813982.
  15. ↑ LATE trial intestigatos. (1993). "Late Assessment of Thrombolytic Efficacy (LATE) study with alteplase 6-24 hours after onset of acute myocardial infarction". Lancet. 342 (8874): 759–66. PMID 8103874.
  16. ↑ Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Ludbrook P; et al. (1987). "Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge". Circulation. 76 (1): 142–54. PMID 3109764.
  17. ↑ 17.0 17.1 17.2 17.3 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)
  18. ↑ Nallamothu BK, Bates ER (2003). "Percutaneous coronary intervention versus fibrinolytic therapy in acute myocardial infarction: is timing (almost) everything?". Am. J. Cardiol. 92 (7): 824–6. PMID 14516884. Unknown parameter |month= ignored (help)
  19. ↑ Pinto DS, Kirtane AJ, Nallamothu BK; et al. (2006). "Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reperfusion strategy". Circulation. 114 (19): 2019–25. doi:10.1161/CIRCULATIONAHA.106.638353. PMID 17075010. Unknown parameter |month= ignored (help)
  20. ↑ Chareonthaitawee P, Gibbons RJ, Roberts RS, Christian TF, Burns R, Yusuf S (2000). "The impact of time to thrombolytic treatment on outcome in patients with acute myocardial infarction. For the CORE investigators (Collaborative Organisation for RheothRx Evaluation)". Heart. 84 (2): 142–8. PMC 1760917. PMID 10908248. Unknown parameter |month= ignored (help)
  21. ↑ McNamara RL, Herrin J, Wang Y; et al. (2007). "Impact of delay in door-to-needle time on mortality in patients with ST-segment elevation myocardial infarction". Am. J. Cardiol. 100 (8): 1227–32. doi:10.1016/j.amjcard.2007.05.043. PMC 2715362. PMID 17920362. Unknown parameter |month= ignored (help)
  22. ↑ Milavetz JJ, Giebel DW, Christian TF, Schwartz RS, Holmes DR, Gibbons RJ (1998). "Time to therapy and salvage in myocardial infarction". J. Am. Coll. Cardiol. 31 (6): 1246–51. PMID 9581715. Unknown parameter |month= ignored (help)
  23. ↑ Newby LK, Rutsch WR, Califf RM; et al. (1996). "Time from symptom onset to treatment and outcomes after thrombolytic therapy. GUSTO-1 Investigators". J. Am. Coll. Cardiol. 27 (7): 1646–55. PMID 8636549. Unknown parameter |month= ignored (help)
  24. ↑ "Effect of intravenous APSAC on mortality after acute myocardial infarction: preliminary report of a placebo-controlled clinical trial. AIMS Trial Study Group". Lancet. 1 (8585): 545–9. 1988. PMID 2894490. Unknown parameter |month= ignored (help)
  25. ↑ 25.0 25.1 "Randomised trial of late thrombolysis in patients with suspected acute myocardial infarction. EMERAS (Estudio Multicéntrico Estreptoquinasa Repúblicas de América del Sur) Collaborative Group". Lancet. 342 (8874): 767–72. 1993. PMID 8103875. Unknown parameter |month= ignored (help)
  26. ↑ 26.0 26.1 26.2 "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)
  27. ↑ "Late Assessment of Thrombolytic Efficacy (LATE) study with alteplase 6-24 hours after onset of acute myocardial infarction". Lancet. 342 (8874): 759–66. 1993. PMID 8103874. Unknown parameter |month= ignored (help)
  28. ↑ Rossi P, Bolognese L (1991). "Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group". Am. J. Cardiol. 68 (6): 585–92. PMID 1877476. Unknown parameter |month= ignored (help)
  29. ↑ "A prospective trial of intravenous streptokinase in acute myocardial infarction (I.S.A.M.). Mortality, morbidity, and infarct size at 21 days. The I.S.A.M. Study Group". N. Engl. J. Med. 314 (23): 1465–71. 1986. doi:10.1056/NEJM198606053142301. PMID 2871492. Unknown parameter |month= ignored (help)
  30. ↑ de Winter RJ, Verouden NJ, Wellens HJ, Wilde AA (2008). "A new ECG sign of proximal LAD occlusion". N. Engl. J. Med. 359 (19): 2071–3. doi:10.1056/NEJMc0804737. PMID 18987380. Unknown parameter |month= ignored (help)
  31. ↑ "Early effects of tissue-type plasminogen activator added to conventional therapy on the culprit coronary lesion in patients presenting with ischemic cardiac pain at rest. Results of the Thrombolysis in Myocardial Ischemia (TIMI IIIA) Trial". Circulation. 87 (1): 38–52. 1993. PMID 8419023. Unknown parameter |month= ignored (help)
  32. ↑ Barrabés JA, Figueras J, Moure C, Cortadellas J, Soler-Soler J (2003). "Prognostic value of lead aVR in patients with a first non-ST-segment elevation acute myocardial infarction". Circulation. 108 (7): 814–9. doi:10.1161/01.CIR.0000084553.92734.83. PMID 12885742. Unknown parameter |month= ignored (help)
  33. ↑ Jong GP, Ma T, Chou P, Shyu MY, Tseng WK, Chang TC (2006). "Reciprocal changes in 12-lead electrocardiography can predict left main coronary artery lesion in patients with acute myocardial infarction". Int Heart J. 47 (1): 13–20. PMID 16479036. Unknown parameter |month= ignored (help)
  34. ↑ 34.0 34.1 34.2 Chen ZM, Jiang LX, Chen YP; et al. (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. Unknown parameter |month= ignored (help)
  35. ↑ 35.0 35.1 35.2 Sabatine MS, Cannon CP, Gibson CM; et al. (2005). "Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation". N. Engl. J. Med. 352 (12): 1179–89. doi:10.1056/NEJMoa050522. PMID 15758000. Unknown parameter |month= ignored (help)
  36. ↑ "Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients". BMJ. 324 (7329): 71–86. 2002. PMC 64503. PMID 11786451. Unknown parameter |month= ignored (help)
  37. ↑ Smith SC, Benjamin EJ, Bonow RO; et al. (2011). "AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation". Circulation. 124 (22): 2458–73. doi:10.1161/CIR.0b013e318235eb4d. PMID 22052934. Unknown parameter |month= ignored (help)
  38. ↑ Serebruany VL, Steinhubl SR, Berger PB; et al. (2005). "Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials". Am. J. Cardiol. 95 (10): 1218–22. doi:10.1016/j.amjcard.2005.01.049. PMID 15877994. Unknown parameter |month= ignored (help)
  39. ↑ Steinhubl SR, Bhatt DL, Brennan DM; et al. (2009). "Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding". Ann. Intern. Med. 150 (6): 379–86. PMID 19293071. Unknown parameter |month= ignored (help)
  40. ↑ 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 (2004). "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)". Circulation. 110 (9): e82–292. PMID 15339869. Unknown parameter |month= ignored (help)
  41. ↑ Antman EM, Hand M, Armstrong PW; et al. (2008). "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". Circulation. 117 (2): 296–329. doi:10.1161/CIRCULATIONAHA.107.188209. PMID 18071078. Unknown parameter |month= ignored (help)

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