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(/* 2013 Revised and 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (DO NOT EDIT){{cite journal |author=O'Gara PT, Kushner FG, Ascheim DD, et al. |title=2013 ACCF/AHA Guideline f...)
 
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{{ST elevation myocardial infarction}}
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'''Associate Editor-In-Chief:''' {{CZ}}


{{EJ}}
==Overview==
Antiplatelet therapy with [[aspirin]] is a mainstay of pharmacotherapy in STEMI. In the International Study of Infarct Survival 2 (ISIS 2), aspirin reduced [[mortality]] in [[STEMI]] as much as [[streptokinase]] (by approximately 25%) when compared to the administration of neither agent. <ref name="pmid2903874">{{cite journal |author= |title=Randomized 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=J. Am. Coll. Cardiol. |volume=12 |issue=6 Suppl A |pages=3A–13A |year=1988 |month=December |pmid=2903874 |doi= |url=}}</ref>  Full doses of non-enteric coated aspirin should be administered as soon as possible to patients with STEMI if there are no contraindications.


==Overview==
==Indications==
Antiplatelet therapy with aspirin is a mainstay of pharmacotherapy in STEMI. In the International Study of Infarct Survival 2 (ISIS 2), [[aspirin]] reduced mortality in [[STEMI]] as much as [[streptokinase]] (by approximately 25%) when compared to the administration of neither agent. <ref name="pmid2903874">{{cite journal |author= |title=Randomized 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=J. Am. Coll. Cardiol. |volume=12 |issue=6 Suppl A |pages=3A–13A |year=1988 |month=December |pmid=2903874 |doi= |url=}}</ref> Full doses of non-enteric coated aspirin should be administered as soon as possible to patients with STEMI if there are no contraindications (history of aspirin allergy or [[anaphylaxis]] to aspirin). Aspirin should be administered irrespective of the reperfusion strategy selected (either [[primary PCI]] or [[fibrinolytic administration]]).
All STEMI patients should receive a full dose of non-enteric coated or intravenous aspirin (162 to 325 mg) within the first 24 hours of presentation. Aspirin should be administered irrespective of the [[reperfusion]] strategy selected (either [[primary PCI]], [[fibrinolytic administration]], or no reperfusion therapy).
 
==Contraindications==
*[[Aspirin]] [[allergy]]
*[[Anaphylaxis]] to [[aspirin]]
*In patients with true aspirin allergy ([[hives]], [[nasal polyps]], [[bronchospasm]], or [[anaphylaxis]]), [[clopidogrel]] or [[ticlopidine]] may be substituted.<ref name="pmid15231615">{{cite journal |author=Pirmohamed M, James S, Meakin S, ''et al'' |title=Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients |journal=BMJ |volume=329 |issue=7456 |pages=15–9 |year=2004 |month=July |pmid=15231615 |pmc=443443 |doi=10.1136/bmj.329.7456.15 |url=}}</ref><ref name="pmid8918275">{{cite journal |author= |title=A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee |journal=[[Lancet]] |volume=348 |issue=9038 |pages=1329–39 |year=1996 |month=November |pmid=8918275 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673696094573 |issn= |accessdate=2010-07-01}}</ref>
It should be noted that prior to hospital discharge, these patients with [[hypersensitivity]] can be treated with
[[aspirin desensitization]].
*Active major [[bleeding]] at a non compressible site is another contraindication.


==Clinical trials supporting the administration of aspirin in STEMI==
==Clinical Trial Data Supporting the Administration of Aspirin in STEMI==
ISIS 2 was a landmark trial which randomized a total of  
ISIS 2 was a landmark trial which randomized a total of  
17,187 patients from 417 hospitals who presented within 24 hours (median 5 h) of STEMI symptom onset to one of 4 strategies:  
17,187 patients from 417 hospitals who presented within 24 hours (median 5 h) of STEMI symptom onset to one of 4 strategies:  
#[[Streptokinase]] (1.5 million units) administered via the intravenous route over 1 hour or
#[[Streptokinase]] (SK) (1.5 million units) administered via the intravenous route over 1 hour or
#Aspirin (enteric coated at a dose of 160 mg/day) for one month or
#Aspirin (ASA) (enteric coated at a dose of 160 mg/day) for one month or
#Both streptokinase and aspirin treatments or
#Both streptokinase and aspirin treatments or
#Neither treatemnt
#Neither treatment


Both [[streptokinase]] alone and aspirin alone were associated with a similar significant reduction in 5 week cardiovascular mortality:  
Both streptokinase alone and aspirin alone were associated with a similar significant reduction in 5 week cardiovascular mortality:  


: 9.2% (791/8592) incidence of cardiovascular deaths among streptokinase versus 12.0% (1029/8595)  among placebo infusion patients (odds reduction: 25% +/- 4; p < 0.00001)  
: 9.2% (791/8592) incidence of cardiovascular [[death]]s among streptokinase versus 12.0% (1029/8595)  among [[placebo]] infusion patients (odds reduction: 25% +/- 4; p < 0.00001)  


: 9.4% (804/8587) incidence of cardiovascular deaths among aspirin versus 11.8% (1016/8600) among placebo tablet patients (odds reduction: 23% +/- 4; p < 0.00001)  
: 9.4% (804/8587) incidence of cardiovascular deaths among aspirin versus 11.8% (1016/8600) among placebo tablet patients (odds reduction: 23% +/- 4; p < 0.00001)  
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The combination of [[streptokinase]] and aspirin was associated with a significant reduction in cardiovascular mortality when compared to the administration of either agent alone (p < 0.0001).  Furthermore, the effect of SK and ASA appeared to be additive as the mortality was only 8.0% (343/4292) among patients treated with both SK and ASA vs 13.2% (568/4300) among those treated with neither agent (42% +/- 5 relative risk reduction; 95% confidence limits 34% to 50%).  
The combination of [[streptokinase]] and aspirin was associated with a significant reduction in cardiovascular mortality when compared to the administration of either agent alone (p < 0.0001).  Furthermore, the effect of SK and ASA appeared to be additive as the mortality was only 8.0% (343/4292) among patients treated with both SK and ASA vs 13.2% (568/4300) among those treated with neither agent (42% +/- 5 relative risk reduction; 95% confidence limits 34% to 50%).  


[[Streptokinase]] was associated with an increased risk of bleeding requiring [[transfusion]] (0.5% versus 0.2%) and [[intracranial hemmorhage]] ([[ICH]]) (0.1% versus 0.0%). Streptokinase was, however, assocaited with fewer non-[[ICH]] strokes (0.6% versus 0.8%).   
Streptokinase was associated with an increased risk of [[bleeding]] requiring [[transfusion]] (0.5% versus 0.2%) and [[intracranial hemorrhage]] ([[ICH]]) (0.1% versus 0.0%). Streptokinase was, however, associated with fewer non-[[ICH]] strokes (0.6% versus 0.8%).   
 
Aspirin was associated with a significant reduction in nonfatal [[reinfarction]] (1.0% versus 2.0%) as well as nonfatal [[stroke]] (0.3% versus 0.6%).  In contrast to [[streptokinase]], [[aspirin]] was not associated with a significant increase in [[intracranial hemorrhage]] or  bleeding requiring [[transfusion]]. Furthermore, while [[streptokinase]] alone was associated with an increased risk of [[reinfarction]].  The addition of aspirin to [[streptokinase]] eliminated of this increased risk of [[reinfarction]] associated with [[streptokinase]] administration.


==History==
Aspirin was associated with a significant reduction in nonfatal [[reinfarction]] (1.0% versus 2.0%) as well as nonfatal [[stroke]] (0.3% versus 0.6%).  In contrast to streptokinase, [[aspirin]] was not associated with a significant increase in [[intracranial hemorrhage]] or  bleeding requiring [[transfusion]]. Furthermore, while streptokinase alone was associated with an increased risk of [[reinfarction]], the addition of aspirin to streptokinase reduced the increased risk of [[reinfarction]] associated with [[streptokinase]] administration.


Medicines containing derivatives of [[salicylic acid]], structurally similar to aspirin, have been in medical use since ancient times. [[Salicylate]]-rich [[willow]] bark extract became recognized for its specific effects on fever, pain and inflammation in the mid-eighteenth century.  By the nineteenth century pharmacists were experimenting with and prescribing a variety of chemicals related to salicylic acid, the active component of willow extract.
==Mechanism(s) of Action==


A French chemist, [[Charles Frederic Gerhardt]], was the first to prepare acetylsalicylic acid in 1853 (patented under the name aspirin on March 6, 1899
===Suppression of Prostaglandins and Thromboxanes===
<ref name=March6>{{cite web |url=http://www.aspirin.com/milestones/1899.htm |title=1899 | work=Wonders of Aspirin | publisher=BAYER | accessdate=March 3, 2009}}</ref>). In the course of his work on the synthesis and properties of various [[acid anhydride]]s, he mixed [[acetyl chloride]] with a [[sodium]] salt of salicylic acid (sodium salicylate). A vigorous reaction ensued, and the resulting melt soon solidified.<ref name=gerhardt>{{de icon}} {{cite journal |author=Gerhardt C |title=Untersuchungen über die wasserfreien organischen Säuren |journal=Annalen der Chemie und Pharmacie|volume=87 |issue= |pages=149–179 |year=1853 |doi=10.1002/jlac.18530870107}}</ref> Since no structural theory existed at that time, Gerhardt called the compound he obtained "salicylic-acetic anhydride" (''wasserfreie Salicylsäure-Essigsäure''). This preparation of aspirin ("salicylic-acetic anhydride") was one of the many reactions Gerhardt conducted for his paper on anhydrides, but he did not pursue it further.
Aspirin's ability to suppress the production of [[prostaglandin]]s and [[thromboxane]]s is due to its irreversible inactivation of the [[cyclooxygenase]] (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an [[acetyl]] group is covalently attached to a [[serine]] residue in the active site of the COX enzyme. This makes aspirin different from other NSAIDs (such as [[diclofenac]] and [[ibuprofen]]), which are reversible inhibitors. It should be noted that [[NSAID]]s compete with aspirin to bind to this serine residue, and this is the mechanism by which a prior dose of a NSAID inhibits the efficacy of aspirin. While inhibition of thromboxane inhibits platelet aggregation, inhibition of prostaglandins may increase the risk of vasoconstriction. Given the potential for vasoconstriction with increasing doses, higher doses of aspirin (325 mg and greater) may not be more effective than doses of 162 to 75 mg.


[[Image:BayerHeroin.png|thumb|right|180px|Advertisement for Aspirin, Heroin, Lycetol, Salophen]]
===COX-1 and COX-2 Inhibition===
Six years later, in 1859, von Gilm obtained analytically pure acetylsalicylic acid (which he called "acetylierte Salicylsäure", ''acetylated salicylic acid'') by a reaction of salicylic acid and acetyl chloride.<ref name=gilm>{{de icon}} {{cite journal |author=von Gilm H |title=Acetylderivate der Phloretin- und Salicylsäure |journal=Annalen der Chemie und Pharmacie|volume=112 |issue=2 |pages=180–185 |year=1859 |doi=10.1002/jlac.18591120207}}</ref> In 1869 Schröder, Prinzhorn and Kraut repeated both Gerhardt's (from sodium salicylate) and von Gilm's (from salicylic acid) syntheses and concluded that both reactions gave the same compound—acetylsalicylic acid. They were first to assign to it the correct structure with the acetyl group connected to the phenolic oxygen.<ref>{{de icon}} {{cite journal |author= Schröder, Prinzhorn, Kraut K |title=Uber Salicylverbindungen |journal=Annalen der Chemie und Pharmacie|volume=150 |issue=1 |pages=1–20 |year=1869 |doi=10.1002/jlac.18691500102}}</ref>
There are at least two different types of [[cyclooxygenase]] (COX): COX-1 and COX-2. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. Normally COX-2 produces prostanoids, most of which are pro-inflammatory. Aspirin-modified COX-2 produces lipoxins, most of which are anti-inflammatory. Newer NSAID drugs called [[COX-2 selective inhibitor]]s have been developed that inhibit only COX-2, with the intent to reduce the incidence of gastrointestinal side-effects.


In 1897, scientists at the drug and dye firm [[Bayer]] began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines. By 1899, Bayer had dubbed this drug ''Aspirin'' and was selling it around the world.<ref>{{cite book  | last = Jeffreys  | first = Diarmuid  | title = Aspirin: The Remarkable Story of a Wonder Drug  | publisher = Bloomsbury USA  | date = August 11, 2005  | pages = 73  | isbn = 1582346003 }}</ref>The name Aspirin is derived from A = Acetyl and "Spirsäure" = an old (German) name for salicylic acid.<ref>Ueber Aspirin. Pflügers Archiv : European journal of physiology, Volume: 84, Issue: 11-12 (March 1, 1901), pp: 527-546.</ref> Aspirin's popularity grew over the first half of the twentieth century, spurred by its effectiveness in the wake of the Spanish flu pandemic of 1918, and aspirin's profitability led to fierce competition and the proliferation of aspirin brands and products, especially after the American patent held by Bayer expired in 1917.<ref>Jeffreys, ''Aspirin'', pp. 136–142 and 151-152</ref><ref>http://www.history.com/this-day-in-history.do?action=VideoArticle&id=52415</ref>
However, several of the new [[COX-2 selective inhibitor]]s, such as [[Vioxx]], have been withdrawn recently, after evidence emerged that COX-2 inhibitors increase the risk of heart attack. It is proposed that endothelial cells lining the microvasculature in the body express COX-2, and, by selectively inhibiting COX-2, prostaglandins (specifically PGI2; [[prostacyclin]]) are down-regulated with respect to thromboxane levels, as COX-1 in platelets is unaffected. Thus, the protective anti-coagulative effect of [[PGI2]] is decreased, increasing the risk of [[thrombus]] and associated [[heart attack]]s and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new COX once aspirin has irreversibly inhibited the enzyme, an important difference with reversible inhibitors.  Utilization of NSAIDs is contraindicated in STEMI, and NSAIDs therapy should be withdrawn in patients with STEMI because of a heightened risk of [[recurrent MI]] and [[congestive heart failure]].


Aspirin's popularity declined after the market releases of [[paracetamol]] (acetaminophen) in 1956 and [[ibuprofen]] in 1969.<ref>Jeffreys, ''Aspirin'', pp. 212–217</ref>  In the 1960s and 1970s, John Vane and others discovered the basic mechanism of aspirin's effects, while clinical trials and other studies from the 1960s to the 1980s established aspirin's efficacy as an anti-clotting agent that reduces the risk of clotting diseases.<ref>Jeffreys, ''Aspirin'', pp. 226–231</ref>  Aspirin sales revived considerably in the last decades of the twentieth century, and remain strong in the twenty-first, thanks to widespread use as a preventive treatment for [[heart attack]]s and [[stroke]]s.<ref>Jeffreys, ''Aspirin'', pp. 267–269</ref>
==Aspirin Dosing==
Full dose aspirin should be administered as soon as possible in the setting of STEMI, including in the pre-hospital setting if there are no contraindications.  There are studies that suggest enteric coating may delay aspirin absorption. <ref>Sagar KA, Smyth MR. Acomparative bioavailability study of different aspirin formulations using on-line multidimensional chromatography. J Pharm Biomed Anal 1999;21:383-92.</ref>  Therefore, non-enteric coated aspirin is recommended in the setting of ST elevation MI. It should also be noted that aspirin can also be administered via the intravenous route.


===Mechanism(s) of Benefit===
===Efficacy and Safety of Low Dose (162 mg) Aspirin versus High Dose (325 mg) Aspirin in STEMI Patients===
Large, prospective, randomized trials randomizing STEMI patients to either low vs high doses of aspirin in STEMI are lacking.  The 30 day mortality and [[bleeding]] risks associated with the administration of 162 mg versus 325 mg [[aspirin]] among patients with [[STEMI]] treated with thrombolytic therapy has been compared in a non-randomized retrospective analysis. <ref name="pmid14671242">{{cite journal |author=Alberts MJ, Bergman DL, Molner E, Jovanovic BD, Ushiwata I, Teruya J |title=Antiplatelet effect of aspirin in patients with cerebrovascular disease |journal=Stroke |volume=35 |issue=1 |pages=175–8 |year=2004 |month=January |pmid=14671242 |doi=10.1161/01.STR.0000106763.46123.F6 |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="pmid18086929">{{cite journal |author=Berger JS, Stebbins A, Granger CB, ''et al'' |title=Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy |journal=Circulation |volume=117 |issue=2 |pages=192–9 |year=2008 |month=January |pmid=18086929 |doi=10.1161/CIRCULATIONAHA.107.729558 |url=}}</ref>
Data for the largest analysis was drawn from a total of 48,422 patients with acute ST segment elevation [[myocardial infarction]] in the GUSTO I and GUSTO III trials (Global Utilization of [[Streptokinase]] and Tissue Plasminogen Activator for Occluded Coronary Arteries). <ref name="pmid18086929">{{cite journal |author=Berger JS, Stebbins A, Granger CB, ''et al'' |title=Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy |journal=Circulation |volume=117 |issue=2 |pages=192–9 |year=2008 |month=January |pmid=18086929 |doi=10.1161/CIRCULATIONAHA.107.729558 |url=}}</ref> 24.4% of patients (n=11 828) were treated in a non-randomized fashio with an initial aspirin dose of 325 mg, and 75.6% (n=36 594) were treated with 162 mg. 24-hour mortality did not differ between the two doses: 2.9% for those receiving an initial aspirin dose of 325 mg versus 2.8% (P=0.894) for those receiving an initial [[aspirin]] dose 162 mg. 7 and 30 day mortality rates were 5.2% versus 4.9% (P=0.118) and 7.1% versus 6.5% (P=0.017) among patients receiving the 325 versus 162 mg aspirin respectively.  After multivariate adjustment for imbalances in baseline characteristics, the initial aspirin dose was not associated with 24-hour (odds ratio [OR], 1.01; 95% CI, 0.82 to 1.25), 7-day (OR, 1.00; 95% CI, 0.87 to 1.17), or 30-day (OR, 0.99; 95% CI, 0.87 to 1.12) mortality rates. No significant difference was noted for [[reinfarction]] or the composite of death or [[reinfarction]] between the two aspirin dose groups. In-hospital moderate/severe bleeding occurred in 9.3% of those treated with 325 mg versus 12.2% among those receiving 162 mg (P<0.001). However, after adjustment for imbalances in baseline characteristics, an initial dose of 325 mg was associated with a significant increase in moderate/severe [[bleeding]] (OR, 1.14; 95% CI, 1.05 to 1.24; P=0.003) compared to an initial does of 162 mg.


[[Acetylation]] of platelet [[cyclooxygenase]]-1 ([[COX-1]]) begins to occur in the portal circulation prior to any measurable systemic level; thus, the measurement of plasma levels of the inactive form of acetylsalicylic acid may be an incomplete measure of efficacy. Nonetheless, peak plasma levels are achieved rapidly, within approximately 30 minutes, followed by rapid clearance with a half-life of 15-20 minutes. The systemic bioavailability of aspirin is about 50% for single oral doses ranging from 20-1300 mg.<ref name="pmid17488967">{{cite journal |author=Campbell CL, Smyth S, Montalescot G, Steinhubl SR |title=Aspirin dose for the prevention of cardiovascular disease: a systematic review |journal=JAMA |volume=297 |issue=18 |pages=2018–24 |year=2007 |month=May |pmid=17488967 |doi=10.1001/jama.297.18.2018 |url=}}</ref>
This non-randomized data from trials conducted many years ago with a substantial use of streptokinase demonstrates that the initial dose of 162 mg [[aspirin]] may be as effective as and perhaps safer than 325 mg for the acute treatment of [[STEMI|ST elevation myocardial infarction]]. These findings require confirmation in large randomized trials of fibrin specific agents before a firm recommendation can be made regarding the optimal initial dose of aspirin in STEMI patients.


Both the beneficial and detrimental effects of aspirin are believed to be primarily due to inhibition of prostanoid biosynthesis, in particular the inhibition of of [[thromboxane A2]] (TXA2) and prostaglandins (e.g., [[PGE2]] and [[PGI2]]).
==2013 Revised and 2007 Focused Update of the ACC/AHA 2004 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, 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><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>==


[[Aspirin]] irreversibly inhibits platelet [[cyclooxygenase]] 1 ([[COX-1]]) through acetylation of the amino acid [[serine]] at position 529, thereby preventing [[arachidonic acid]]'s access to the [[COX-1]] catalytic site through steric hindrance. By inhibiting [[COX-1]], the platelet is unable to synthesize prostaglandin H2, which, under normal circumstances, is then converted to [[thromboxane A2]] ([[thromboxane A2|TXA2]]) via the enzyme Thromboxane synthase. Although anucleate platelets possess some capacity for protein synthesis, they are incapable of overcoming [[COX-1]] inhibition with new protein synthesis, and the [[aspirin]]-induced defect spans the 8 to 10 day life span of the platelet. Because of platelet turnover, approximately 10% of platelets with normal COX activity will be recovered daily following cessation of [[aspirin]] therapy. Therefore, up to 10 days can be required for complete recovery of platelet COX activity; however, it may require only 20% of normal COX activity to exhibit normal hemostasis.<ref name="pmid1531663">{{cite journal |author=Roux S, Christeller S, Lüdin E |title=Effects of aspirin on coronary reocclusion and recurrent ischemia after thrombolysis: a meta-analysis |journal=J. Am. Coll. Cardiol. |volume=19 |issue=3 |pages=671–7 |year=1992 |month=March |pmid=1531663 |doi= |url=}}</ref><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=http://bmj.com/cgi/pmidlookup?view=long&pmid=11786451}}</ref><ref name="pmid10703994">{{cite journal |author=Sagar KA, Smyth MR |title=A comparative bioavailability study of different aspirin formulations using on-line multidimensional chromatography |journal=J Pharm Biomed Anal |volume=21 |issue=2 |pages=383–92 |year=1999 |month=November |pmid=10703994 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0731-7085(99)00177-6}}</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>
{|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 should be given before [[primary PCI]].<ref name="pmid18819961">{{cite journal |author=Jolly SS, Pogue J, Haladyn K, ''et al.'' |title=Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study |journal=Eur. Heart J. |volume=30 |issue=8 |pages=900–7 |year=2009 |month=April |pmid=18819961 |doi=10.1093/eurheartj/ehn417 |url=}}</ref><ref name="pmid2954724">{{cite journal |author=Barnathan ES, Schwartz JS, Taylor L, ''et al.'' |title=Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty |journal=Circulation |volume=76 |issue=1 |pages=125–34 |year=1987 |month=July |pmid=2954724 |doi= |url=}}</ref><ref name="pmid20818903">{{cite journal |author=Mehta SR, Bassand JP, Chrolavicius S, ''et al.'' |title=Dose comparisons of clopidogrel and aspirin in acute coronary syndromes |journal=N. Engl. J. Med. |volume=363 |issue=10 |pages=930–42 |year=2010 |month=September |pmid=20818903 |doi=10.1056/NEJMoa0909475 |url=}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' After PCI, aspirin should be continued indefinitely.<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="pmid8598866">{{cite journal |author=Schömig A, Neumann FJ, Kastrati A, ''et al.'' |title=A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents |journal=N. Engl. J. Med. |volume=334 |issue=17 |pages=1084–9 |year=1996 |month=April |pmid=8598866 |doi=10.1056/NEJM199604253341702 |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>  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' For all post-PCI STEMI stented patients without aspirin resistance, [[allergy]], or increased risk of [[bleeding]], aspirin 162 mg to 325 mg daily should be given for at least 1 month after BMS implantation, 3 months after [[sirolimus-eluting stent]] implantation, and 6 months after [[paclitaxel-eluting stent]] implantation, after which long-term aspirin use should be continued indefinitely at a dose of 75 mg to 162 mg daily. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' 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>'''5.''' 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>
|}


[[COX-1]] is constitutively expressed in most cells and plays important roles beyond [[TXA2]] production in platelets. Of particular importance is the production of the cytoprotective prostaglandins by gastric mucosa. Unlike platelets, gastric mucosal cells possess the biosynthetic machinery necessary to overcome [[COX-1]] inhibition and, therefore, recover the ability to synthesize prostaglandins within a few hours after exposure to [[aspirin]]. [[COX-2]], a second cyclo oxygenase isoenzyme primarily responsible for synthesis of the platelet inhibitor PGI2 by endothelial cells and induced in response to inflammatory stimuli, is less sensitive to the effects of aspirin. [[Aspirin]] is 170 fold less effective at inhibiting [[COX-2]] than [[COX-1]].
{|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 81 mg of aspirin per day in preference to higher maintenance doses after primary PCI.<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="pmid20818903">{{cite journal |author=Mehta SR, Bassand JP, Chrolavicius S, ''et al.'' |title=Dose comparisons of clopidogrel and aspirin in acute coronary syndromes |journal=N. Engl. J. Med. |volume=363 |issue=10 |pages=930–42 |year=2010 |month=September |pmid=20818903 |doi=10.1056/NEJMoa0909475 |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>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In patients for whom the physician is concerned about risk of bleeding lower-dose 75 mg to 162 mg of [[aspirin]] is reasonable during the initial period after [[stent]] implantation. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]]) '' <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' 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>
|}


At higher doses, [[aspirin]] suppresses vascular endothelial cell production of [[prostacyclin]], which, if unopposed, results in inhibition of platelet aggregation and induces vasodilatation.
===Antiplatelet Therapy to Support PCI After 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>===


It has been postulated that [[aspirin]]’s anti-inflammatory properties may explain at least part of its mechanism of benefit in CVD. However, with [[aspirin]]’s much greater selectivity for [[COX-1]] and the central role of [[COX-2]] in inflammation, dosages that achieve measurable anti-inflammatory activity (up to several grams daily) are much higher than those proven clinically effective in the prevention of atherothrombotic events. Consistent with this is the lack of an effect on high sensitivity C-reactive protein levels in most studies.
{|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.''' After PCI, aspirin should be continued indefinitely.<ref name="pmid20818903">{{cite journal |author=Mehta SR, Bassand JP, Chrolavicius S, ''et al.'' |title=Dose comparisons of clopidogrel and aspirin in acute coronary syndromes |journal=N. Engl. J. Med. |volume=363 |issue=10 |pages=930–42 |year=2010 |month=September |pmid=20818903 |doi=10.1056/NEJMoa0909475 |url=}}</ref><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="pmid20817281">{{cite journal |author=Mehta SR, Tanguay JF, Eikelboom JW, ''et al.'' |title=Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial |journal=Lancet |volume=376 |issue=9748 |pages=1233–43 |year=2010 |month=October |pmid=20817281 |doi=10.1016/S0140-6736(10)61088-4 |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>
|}


Currently, there is no gold standard measure of [[aspirin]]’s pharmacodynamics.
{|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.''' After PCI, it is reasonable to use 81 mg of aspirin per day in preference to higher maintenance doses.<ref name="pmid20818903">{{cite journal |author=Mehta SR, Bassand JP, Chrolavicius S, ''et al.'' |title=Dose comparisons of clopidogrel and aspirin in acute coronary syndromes |journal=N. Engl. J. Med. |volume=363|issue=10 |pages=930–42 |year=2010 |month=September |pmid=20818903 |doi=10.1056/NEJMoa0909475 |url=}}</ref><ref name="pmid20817281">{{cite journal |author=Mehta SR, Tanguay JF, Eikelboom JW, ''et al.'' |title=Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial |journal=Lancet|volume=376 |issue=9748 |pages=1233–43 |year=2010 |month=October |pmid=20817281 |doi=10.1016/S0140-6736(10)61088-4 |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>
|}


There has been only 1 randomized study that directly compared [[aspirin]] dose in [[STEMI]]. The Duke University Clinical Cardiology Group Study-II (DUCCS-II) compared the efficacy of 81 and 325 mg [[aspirin]] doses in 162 patients with [[STEMI]] treated with front loaded [[tissue plasminogen activator]] or an isolated plasminogen [[streptokinase]] activator complex. No effect of [[aspirin]] dose on clinical outcomes was noted; however, because of its early termination, the study was severely underpowered. The majority of data supporting the use of [[aspirin]] in the setting of [[acute myocardial infarction]] are from ISIS-2. In this study, 162.5 mg [[aspirin]] reduced vascular mortality, re-infarction, and stroke without substantially increasing the risk of major bleeding. Other studies of [[aspirin]] in the acute setting of [[myocardial infarction]] have been severely underpowered to address the clinical efficacy and safety profile of [[aspirin]] in this setting.
==See Also==
* [[The Living Guidelines: STEMI | The STEMI Living Guidelines: Vote on current recommendations and suggest revisions to the guidelines]]


A wide range of [[aspirin]] doses, preparations, and methods of ingestion have been evaluated to determine the best way to achieve maximal antiplatelet activity in the acute setting. In a study that evaluated the acute antiplatelet effects of 40 mg, 100 mg, 300 mg, and 500 mg doses of [[aspirin]], the 300 mg and 500 mg doses were found to achieve equal levels of platelet inhibition 2 hours following ingestion, suggesting that there is no added benefit for doses of more than 300 mg. However, at very low doses (0.45 mg/kg, corresponding to about 30 mg in an adult), it may take 10 days to effectively suppress [[Thromboxane A2|TXA2]] production. <ref name="pmid7045161">{{cite journal |author=Patrignani P, Filabozzi P, Patrono C |title=Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects |journal=J. Clin. Invest. |volume=69 |issue=6 |pages=1366–72 |year=1982 |month=June |pmid=7045161 |pmc=370209 |doi= |url=}}</ref>
==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>


[[Aspirin]] absorption and the onset of antiplatelet activity are significantly shortened by chewing or drinking soluble [[aspirin]], with maximal inhibition of serum [[Thromboxane B2]] ([[Thromboxane B2|TXB2]]) production achieved within 20 to 30 minutes compared with swallowing a whole pill that required approximately 60 minutes.
*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>


In another study of 18 volunteers, chewing an 81 mg, 162 mg, or 324 mg [[aspirin]] pill led to equivalent reduction in [[Thromboxane B2|TXB2]] production, but maximal inhibition by 15 minutes after ingestion was achieved only with the 162 mg and 324 mg doses. The results of these and other studies suggest that to rapidly (within 15 minutes) achieve the maximal effects of [[aspirin]], at least 162 mg should be chewed or dissolved, then swallowed.<ref name="pmid7942533">{{cite journal |author=Dabaghi SF, Kamat SG, Payne J, ''et al'' |title=Effects of low-dose aspirin on in vitro platelet aggregation in the early minutes after ingestion in normal subjects |journal=Am. J. Cardiol. |volume=74 |issue=7 |pages=720–3 |year=1994 |month=October |pmid=7942533 |doi= |url=}}</ref><ref name="pmid10468077">{{cite journal |author=Feldman M, Cryer B |title=Aspirin absorption rates and platelet inhibition times with 325-mg buffered aspirin tablets (chewed or swallowed intact) and with buffered aspirin solution |journal=Am. J. Cardiol. |volume=84 |issue=4 |pages=404–9 |year=1999 |month=August |pmid=10468077 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(99)00324-0}}</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>
 
The major risk of [[aspirin]], as with other non steroidal anti inflammatory drugs ([[NSAIDs]]), is the risk of bleeding. Although the antiplatelet effects of [[aspirin]] likely contribute to an increase in the risk of bleeding, as highlighted by an increased risk of hemorrhagic stroke of 0.2 events per 1000 patient years, the majority of the increased bleeding has a gastrointestinal tract etiology.
 
Although this increased risk of gastrointestinal bleeding is more commonly attributed to non [[aspirin]] [[NSAIDs]], a recent evaluation of patients hospitalized for ulcer bleeding found that low-dose aspirin therapy was responsible for as much ulcer bleeding as all other [[NSAID]]s combined. In another prospective evaluation of 18 820 hospitalized patients, 1225 were admitted as a result of adverse drug reactions, and low-dose [[aspirin]] was identified as one of the most common causal agents, with 18% of the hospitalizations and 61% of the fatal cases associated with [[aspirin]].<ref name="pmid17239674">{{cite journal |author=Hovens MM, Snoep JD, Eikenboom JC, van der Bom JG, Mertens BJ, Huisman MV |title=Prevalence of persistent platelet reactivity despite use of aspirin: a systematic review |journal=Am. Heart J. |volume=153 |issue=2 |pages=175–81 |year=2007 |month=February |pmid=17239674 |doi=10.1016/j.ahj.2006.10.040 |url=}}</ref><ref name="pmid15996977">{{cite journal |author=Jochmann N, Stangl K, Garbe E, Baumann G, Stangl V |title=Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases |journal=Eur. Heart J. |volume=26 |issue=16 |pages=1585–95 |year=2005 |month=August |pmid=15996977 |doi=10.1093/eurheartj/ehi397 |url=}}</ref><ref name="pmid16551714">{{cite journal |author=Becker DM, Segal J, Vaidya D, ''et al'' |title=Sex differences in platelet reactivity and response to low-dose aspirin therapy |journal=JAMA |volume=295 |issue=12 |pages=1420–7 |year=2006 |month=March |pmid=16551714 |doi=10.1001/jama.295.12.1420 |url=}}</ref><ref name="pmid16418466">{{cite journal |author=Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL |title=Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials |journal=JAMA |volume=295 |issue=3 |pages=306–13 |year=2006 |month=January |pmid=16418466 |doi=10.1001/jama.295.3.306 |url=}}</ref>
 
An analysis of [[aspirin]]-treated patients from the UKTIA trial found almost double the risk of gastrointestinal bleeding among patients randomized to 1200 mg/day of aspirin compared with 300 mg/day. In the Dutch-TIA trial, where the higher [[aspirin]] dose was more reflective of contemporary dosing, a trend toward less bleeding was noted in the 30 mg group (2.6%) than the 283 mg group (3.2%).
 
Observational data from the BRAVO (Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion) and CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trials also demonstrated an increased risk of bleeding with higher doses of [[aspirin]], even when doses no greater than 325 mg were used.<ref name="pmid12874182">{{cite journal |author=Topol EJ, Easton D, Harrington RA, ''et al'' |title=Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease |journal=Circulation |volume=108 |issue=4 |pages=399–406 |year=2003 |month=July |pmid=12874182 |doi=10.1161/01.CIR.0000084501.48570.F6 |url=}}</ref><ref name="pmid15028352">{{cite journal |author=Quinn MJ, Aronow HD, Califf RM, ''et al'' |title=Aspirin dose and six-month outcome after an acute coronary syndrome |journal=J. Am. Coll. Cardiol. |volume=43 |issue=6 |pages=972–8 |year=2004 |month=March |pmid=15028352 |doi=10.1016/j.jacc.2003.09.059 |url=}}</ref>
 
===Dosing===
If not given prior to hospital admission, [[Aspirin]] should be administered to all patients at a dose of 162 to 325 mg to chew and swallow, unless there is a compelling contraindication (e.g., history of anaphylactic reaction). [[Aspirin]] is generally administered orally and is rapidly absorbed in the stomach and upper intestine. Enteric coating may delay the absorption, and it is for this reason that not enteric coated aspirin is often administered in the setting of ST elevation MI. It should also be noted that aspirin can also be administered via the intravenous route.<ref name="pmid18086929">{{cite journal |author=Berger JS, Stebbins A, Granger CB, ''et al'' |title=Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy |journal=Circulation |volume=117 |issue=2 |pages=192–9 |year=2008 |month=January |pmid=18086929 |doi=10.1161/CIRCULATIONAHA.107.729558 |url=}}</ref>
 
====Efficacy and safety of low dose (162 mg) aspirin versus high dose (325 mg) aspirin in STEMI patients====
Large, prospective, randomized trials randomizing STEMI patients to either low vs high doses of aspirin in STEMI are lacking.  The 30 day mortality and [[bleeding]] risks associated with the administration of 162 mg versus 325 mg [[aspirin]] among patients with [[STEMI]] treated with thrombolytic therapy has been compared in a non-randomized retrospective analysis. <ref name="pmid14671242">{{cite journal |author=Alberts MJ, Bergman DL, Molner E, Jovanovic BD, Ushiwata I, Teruya J |title=Antiplatelet effect of aspirin in patients with cerebrovascular disease |journal=Stroke |volume=35 |issue=1 |pages=175–8 |year=2004 |month=January |pmid=14671242 |doi=10.1161/01.STR.0000106763.46123.F6 |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>
Data for the analysis was drawn from a total of 48,422 patients with acute ST segment elevation [[myocardial infarction]] in the GUSTO I and GUSTO III trials (Global Utilization of [[Streptokinase]] and Tissue Plasminogen Activator for Occluded Coronary Arteries).  24.4% of patients (n=11 828) were treated in a non-randomized fashio with an initial aspirin dose of 325 mg, and 75.6% (n=36 594) were treated with 162 mg. 24-hour mortality did not differ between the two doses: 2.9% for those receiving an initial [[aspirin]] dose of 325 mg versus 2.8% (P=0.894) for those receiving an initial [[aspirin]] dose 162 mg. 7 and 30 day mortality rates were 5.2% versus 4.9% (P=0.118) and 7.1% versus 6.5% (P=0.017) among patients receiving the 325 versus 162 mg [[aspirin]] respectively.  After multivariate adjustment for imbalances in baseline characteristics, the initial [[aspirin]] dose was not associated with 24-hour (odds ratio [OR], 1.01; 95% CI, 0.82 to 1.25), 7-day (OR, 1.00; 95% CI, 0.87 to 1.17), or 30-day (OR, 0.99; 95% CI, 0.87 to 1.12) mortality rates. No significant difference was noted for [[reinfarction]] or the composite of death or [[reinfarction]] between the two aspirin dose groups. In-hospital moderate/severe bleeding occurred in 9.3% of those treated with 325 mg versus 12.2% among those receiving 162 mg (P<0.001). However, after adjustment for imbalances in baseline characteristics, an initial dose of 325 mg was associated with a significant increase in moderate/severe [[bleeding]] (OR, 1.14; 95% CI, 1.05 to 1.24; P=0.003) compared to an initial does of 162 mg.
 
This non-randomized data from trials conducted many years ago with a substantial use of streptokinase demonstrates that the initial dose of 162 mg [[aspirin]] may be as effective as and perhaps safer than 325 mg for the acute treatment of [[STEMI|ST elevation myocardial infarction]]. These findings require confirmation in large randomized trials before a firm recommendation can be made regarding the optimal initial dose of aspirin in STEMI patients.
 
===Side Effects and Contraindications===
 
The use of [[aspirin]] is contraindicated in those with a hypersensitivity to salicylate.
 
Aspirin suppositories (300 mg) can be used safely and are the recommended route of administration for patients with severe nausea and vomiting or known upper-gastrointestinal disorders.
 
In patients with true [[aspirin]] allergy ([[hives]], [[nasal polyps]], [[bronchospasm]], or [[anaphylaxis]]), [[clopidogrel]] or [[ticlopidine]] may be substituted.<ref name="pmid15231615">{{cite journal |author=Pirmohamed M, James S, Meakin S, ''et al'' |title=Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients |journal=BMJ |volume=329 |issue=7456 |pages=15–9 |year=2004 |month=July |pmid=15231615 |pmc=443443 |doi=10.1136/bmj.329.7456.15 |url=}}</ref>
 
==Guidelines (DO NOT EDIT)==
 
===Class I===
 
* For all post [[Percutaneous Coronary Intervention]]s ([[PCI]]) stented [[STEMI]] patients without [[aspirin]] resistance, [[allergy]], or increased risk of [[bleeding]], [[aspirin]] 162 mg to 325 mg daily should be given for at least 1 month after bare metal stent (BMS) implantation, 3 months after [[Sirolimus]] eluting stent implantation (SES), and 6 months after [[Paclitaxel]] eluting stent implantation (PES), after which long term [[aspirin]] use should be continued indefinitely at a dose of 75 mg to 162 mg daily. '''Class I (Level of Evidence: B)'''<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>
 
===Class IIa===
 
* In patients for whom the physician is concerned about risk of bleeding lower-dose 75 mg to 162 mg of [[aspirin]] is reasonable during the initial period after stent implantation. '''Class IIa (Level of Evidence: C)'''<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>


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


{{STEMI}}
[[Category:Disease]]
 
[[Category:Cardiology]]
[[Category:Cardiology]]
[[Category:Ischemic heart diseases]]
[[Category:Intensive care medicine]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]


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Latest revision as of 16:53, 7 November 2016

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

Overview

Antiplatelet therapy with aspirin is a mainstay of pharmacotherapy in STEMI. In the International Study of Infarct Survival 2 (ISIS 2), aspirin reduced mortality in STEMI as much as streptokinase (by approximately 25%) when compared to the administration of neither agent. [1] Full doses of non-enteric coated aspirin should be administered as soon as possible to patients with STEMI if there are no contraindications.

Indications

All STEMI patients should receive a full dose of non-enteric coated or intravenous aspirin (162 to 325 mg) within the first 24 hours of presentation. Aspirin should be administered irrespective of the reperfusion strategy selected (either primary PCI, fibrinolytic administration, or no reperfusion therapy).

Contraindications

It should be noted that prior to hospital discharge, these patients with hypersensitivity can be treated with aspirin desensitization.

  • Active major bleeding at a non compressible site is another contraindication.

Clinical Trial Data Supporting the Administration of Aspirin in STEMI

ISIS 2 was a landmark trial which randomized a total of 17,187 patients from 417 hospitals who presented within 24 hours (median 5 h) of STEMI symptom onset to one of 4 strategies:

  1. Streptokinase (SK) (1.5 million units) administered via the intravenous route over 1 hour or
  2. Aspirin (ASA) (enteric coated at a dose of 160 mg/day) for one month or
  3. Both streptokinase and aspirin treatments or
  4. Neither treatment

Both streptokinase alone and aspirin alone were associated with a similar significant reduction in 5 week cardiovascular mortality:

9.2% (791/8592) incidence of cardiovascular deaths among streptokinase versus 12.0% (1029/8595) among placebo infusion patients (odds reduction: 25% +/- 4; p < 0.00001)
9.4% (804/8587) incidence of cardiovascular deaths among aspirin versus 11.8% (1016/8600) among placebo tablet patients (odds reduction: 23% +/- 4; p < 0.00001)

The combination of streptokinase and aspirin was associated with a significant reduction in cardiovascular mortality when compared to the administration of either agent alone (p < 0.0001). Furthermore, the effect of SK and ASA appeared to be additive as the mortality was only 8.0% (343/4292) among patients treated with both SK and ASA vs 13.2% (568/4300) among those treated with neither agent (42% +/- 5 relative risk reduction; 95% confidence limits 34% to 50%).

Streptokinase was associated with an increased risk of bleeding requiring transfusion (0.5% versus 0.2%) and intracranial hemorrhage (ICH) (0.1% versus 0.0%). Streptokinase was, however, associated with fewer non-ICH strokes (0.6% versus 0.8%).

Aspirin was associated with a significant reduction in nonfatal reinfarction (1.0% versus 2.0%) as well as nonfatal stroke (0.3% versus 0.6%). In contrast to streptokinase, aspirin was not associated with a significant increase in intracranial hemorrhage or bleeding requiring transfusion. Furthermore, while streptokinase alone was associated with an increased risk of reinfarction, the addition of aspirin to streptokinase reduced the increased risk of reinfarction associated with streptokinase administration.

Mechanism(s) of Action

Suppression of Prostaglandins and Thromboxanes

Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme. This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors. It should be noted that NSAIDs compete with aspirin to bind to this serine residue, and this is the mechanism by which a prior dose of a NSAID inhibits the efficacy of aspirin. While inhibition of thromboxane inhibits platelet aggregation, inhibition of prostaglandins may increase the risk of vasoconstriction. Given the potential for vasoconstriction with increasing doses, higher doses of aspirin (325 mg and greater) may not be more effective than doses of 162 to 75 mg.

COX-1 and COX-2 Inhibition

There are at least two different types of cyclooxygenase (COX): COX-1 and COX-2. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. Normally COX-2 produces prostanoids, most of which are pro-inflammatory. Aspirin-modified COX-2 produces lipoxins, most of which are anti-inflammatory. Newer NSAID drugs called COX-2 selective inhibitors have been developed that inhibit only COX-2, with the intent to reduce the incidence of gastrointestinal side-effects.

However, several of the new COX-2 selective inhibitors, such as Vioxx, have been withdrawn recently, after evidence emerged that COX-2 inhibitors increase the risk of heart attack. It is proposed that endothelial cells lining the microvasculature in the body express COX-2, and, by selectively inhibiting COX-2, prostaglandins (specifically PGI2; prostacyclin) are down-regulated with respect to thromboxane levels, as COX-1 in platelets is unaffected. Thus, the protective anti-coagulative effect of PGI2 is decreased, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new COX once aspirin has irreversibly inhibited the enzyme, an important difference with reversible inhibitors. Utilization of NSAIDs is contraindicated in STEMI, and NSAIDs therapy should be withdrawn in patients with STEMI because of a heightened risk of recurrent MI and congestive heart failure.

Aspirin Dosing

Full dose aspirin should be administered as soon as possible in the setting of STEMI, including in the pre-hospital setting if there are no contraindications. There are studies that suggest enteric coating may delay aspirin absorption. [4] Therefore, non-enteric coated aspirin is recommended in the setting of ST elevation MI. It should also be noted that aspirin can also be administered via the intravenous route.

Efficacy and Safety of Low Dose (162 mg) Aspirin versus High Dose (325 mg) Aspirin in STEMI Patients

Large, prospective, randomized trials randomizing STEMI patients to either low vs high doses of aspirin in STEMI are lacking. The 30 day mortality and bleeding risks associated with the administration of 162 mg versus 325 mg aspirin among patients with STEMI treated with thrombolytic therapy has been compared in a non-randomized retrospective analysis. [5][6][7] Data for the largest analysis was drawn from a total of 48,422 patients with acute ST segment elevation myocardial infarction in the GUSTO I and GUSTO III trials (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries). [7] 24.4% of patients (n=11 828) were treated in a non-randomized fashio with an initial aspirin dose of 325 mg, and 75.6% (n=36 594) were treated with 162 mg. 24-hour mortality did not differ between the two doses: 2.9% for those receiving an initial aspirin dose of 325 mg versus 2.8% (P=0.894) for those receiving an initial aspirin dose 162 mg. 7 and 30 day mortality rates were 5.2% versus 4.9% (P=0.118) and 7.1% versus 6.5% (P=0.017) among patients receiving the 325 versus 162 mg aspirin respectively. After multivariate adjustment for imbalances in baseline characteristics, the initial aspirin dose was not associated with 24-hour (odds ratio [OR], 1.01; 95% CI, 0.82 to 1.25), 7-day (OR, 1.00; 95% CI, 0.87 to 1.17), or 30-day (OR, 0.99; 95% CI, 0.87 to 1.12) mortality rates. No significant difference was noted for reinfarction or the composite of death or reinfarction between the two aspirin dose groups. In-hospital moderate/severe bleeding occurred in 9.3% of those treated with 325 mg versus 12.2% among those receiving 162 mg (P<0.001). However, after adjustment for imbalances in baseline characteristics, an initial dose of 325 mg was associated with a significant increase in moderate/severe bleeding (OR, 1.14; 95% CI, 1.05 to 1.24; P=0.003) compared to an initial does of 162 mg.

This non-randomized data from trials conducted many years ago with a substantial use of streptokinase demonstrates that the initial dose of 162 mg aspirin may be as effective as and perhaps safer than 325 mg for the acute treatment of ST elevation myocardial infarction. These findings require confirmation in large randomized trials of fibrin specific agents before a firm recommendation can be made regarding the optimal initial dose of aspirin in STEMI patients.

2013 Revised and 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (DO NOT EDIT)[8] [9][10]

Class I
"1. Aspirin 162 to 325 mg should be given before primary PCI.[11][12][13] (Level of Evidence: B)"
"2. After PCI, aspirin should be continued indefinitely.[14][15][16] (Level of Evidence: A)"
"3. For all post-PCI STEMI stented patients without aspirin resistance, allergy, or increased risk of bleeding, aspirin 162 mg to 325 mg daily should be given for at least 1 month after BMS implantation, 3 months after sirolimus-eluting stent implantation, and 6 months after paclitaxel-eluting stent implantation, after which long-term aspirin use should be continued indefinitely at a dose of 75 mg to 162 mg daily. (Level of Evidence: B) "
"4. 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.[17][18][19](Level of Evidence: A) "
"5. Aspirin should be continued indefinitely [17][18][19](Level of Evidence: A) and clopidogrel (75 mg daily) should be continued for at least 14 days [18][19](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 81 mg of aspirin per day in preference to higher maintenance doses after primary PCI.[14][13][6][20](Level of Evidence: B)"
"2. In patients for whom the physician is concerned about risk of bleeding lower-dose 75 mg to 162 mg of aspirin is reasonable during the initial period after stent implantation. (Level of Evidence: C) "
"3. It is reasonable to use aspirin 81 mg per day in preference to higher maintenance doses after fibrinolytic therapy.[14][16][6][20](Level of Evidence: B) "

Antiplatelet Therapy to Support PCI After Fibrinolytic Therapy (DO NOT EDIT)[8]

Class I
"1. After PCI, aspirin should be continued indefinitely.[13][14][16][21][18][19](Level of Evidence: A) "
Class IIa
"1. After PCI, it is reasonable to use 81 mg of aspirin per day in preference to higher maintenance doses.[13][21][6][20](Level of Evidence: B) "

See Also

Sources

  • The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction [22]
  • The 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction [10]
  • 2013 Revised ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction[8]

References

  1. ↑ "Randomized 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". J. Am. Coll. Cardiol. 12 (6 Suppl A): 3A–13A. 1988. PMID 2903874. Unknown parameter |month= ignored (help)
  2. ↑ Pirmohamed M, James S, Meakin S; et al. (2004). "Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients". BMJ. 329 (7456): 15–9. doi:10.1136/bmj.329.7456.15. PMC 443443. PMID 15231615. Unknown parameter |month= ignored (help)
  3. ↑ "A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee". Lancet. 348 (9038): 1329–39. 1996. PMID 8918275. Retrieved 2010-07-01. Unknown parameter |month= ignored (help)
  4. ↑ Sagar KA, Smyth MR. Acomparative bioavailability study of different aspirin formulations using on-line multidimensional chromatography. J Pharm Biomed Anal 1999;21:383-92.
  5. ↑ Alberts MJ, Bergman DL, Molner E, Jovanovic BD, Ushiwata I, Teruya J (2004). "Antiplatelet effect of aspirin in patients with cerebrovascular disease". Stroke. 35 (1): 175–8. doi:10.1161/01.STR.0000106763.46123.F6. PMID 14671242. Unknown parameter |month= ignored (help)
  6. ↑ 6.0 6.1 6.2 6.3 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)
  7. ↑ 7.0 7.1 Berger JS, Stebbins A, Granger CB; et al. (2008). "Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy". Circulation. 117 (2): 192–9. doi:10.1161/CIRCULATIONAHA.107.729558. PMID 18086929. Unknown parameter |month= ignored (help)
  8. ↑ 8.0 8.1 8.2 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)
  9. ↑ Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M; 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.
  10. ↑ 10.0 10.1 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)
  11. ↑ Jolly SS, Pogue J, Haladyn K; et al. (2009). "Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study". Eur. Heart J. 30 (8): 900–7. doi:10.1093/eurheartj/ehn417. PMID 18819961. Unknown parameter |month= ignored (help)
  12. ↑ Barnathan ES, Schwartz JS, Taylor L; et al. (1987). "Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty". Circulation. 76 (1): 125–34. PMID 2954724. Unknown parameter |month= ignored (help)
  13. ↑ 13.0 13.1 13.2 13.3 Mehta SR, Bassand JP, Chrolavicius S; et al. (2010). "Dose comparisons of clopidogrel and aspirin in acute coronary syndromes". N. Engl. J. Med. 363 (10): 930–42. doi:10.1056/NEJMoa0909475. PMID 20818903. Unknown parameter |month= ignored (help)
  14. ↑ 14.0 14.1 14.2 14.3 "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)
  15. ↑ Schömig A, Neumann FJ, Kastrati A; et al. (1996). "A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents". N. Engl. J. Med. 334 (17): 1084–9. doi:10.1056/NEJM199604253341702. PMID 8598866. Unknown parameter |month= ignored (help)
  16. ↑ 16.0 16.1 16.2 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)
  17. ↑ 17.0 17.1 "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)
  18. ↑ 18.0 18.1 18.2 18.3 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)
  19. ↑ 19.0 19.1 19.2 19.3 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)
  20. ↑ 20.0 20.1 20.2 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)
  21. ↑ 21.0 21.1 Mehta SR, Tanguay JF, Eikelboom JW; et al. (2010). "Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial". Lancet. 376 (9748): 1233–43. doi:10.1016/S0140-6736(10)61088-4. PMID 20817281. Unknown parameter |month= ignored (help)
  22. ↑ 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)


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