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Evidence summaries

Clopidogrel and Aspirin in Acute ST-Segment Elevation Myocardial Infarction (STEMI)

Addition of clopidogrel to aspirin with other standard treatments reduces mortality and major vascular events in patients with acute STEMI. Level of evidence: "A"

A multicentre RCT 1 of 45 852 patients with acute myocardial infarction was carried out in 1 250 hospitals in China. Patients admitted to care within 24 h of suspected infarction onset were randomly allocated to clopidogrel 75 mg daily or placebo in addition to aspirin 162 mg daily. 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Clopidogrel produced a 9% (95% CI 3-14) proportional reduction in death, reinfarction, or stroke (2 121 [9.2%] clopidogrel vs. 2 310 [10.1%] placebo; p=0.002), corresponding to 9 fewer events per 1 000 patients treated for about 2 weeks, as well as a 7% (1-13) proportional reduction in any death (1 726 [7.5%] vs. 1 845 [8.1%]; p=0.03). No significant excess risk was noted with clopidogrel, either overall (134 [0.58%] vs. 125 [0.55%]; p=0.59), or in patients aged older than 70 years or in those given fibrinolytic therapy.

In a multicentre placebo-controlled RCT of clopidogrel in patients receiving fibrinolytics for STEMI, a prospectively planned analysis of the 1 863 patients undergoing PCI after mandated angiography was performed 2. Patients received aspirin and were randomized to either clopidogrel (300 mg loading dose, then 75 mg once daily) or placebo initiated with fibrinolysis and given until coronary angiography was performed after 2 to 8 days. During 30 days follow-up, pretreatment with clopidogrel resulted in a reduction in cardiovascular death, MI, or stroke: 70 (7.5%) vs. 112 (12.0%), adjusted OR 0.59 (95% CI, 0.43-0.81); p =0.001; NNT=23. The reduction was evident both prior to PCI (OR 0.62) and following PCI (OR 0.54). There was no significant excess in the rates of major or minor bleeding (18 (2.0%) vs. 17 (1.9%); P>0.99).

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    References

    • Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, Collins R, Liu LS, COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005 Nov 5;366(9497):1607-21. [PubMed]
    • Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E, Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005 Sep 14;294(10):1224-32. [PubMed]

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