Authors
Sabatine MS, Cannon CP, Gibson CM, et al.
Title
Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-segment Elevation
References
N Engl J Med 2005;352:1179-1189.
Background
Despite fibrinolytic therapy for ST-elevation myocardial infarction, there continues to be situations of inadequate reperfusion or reocclusion resulting in mortality.
Purpose
To determine whether clopidogrel is useful in patients with ST-elevation myocardial infarction, in addition to fibrinolysis and aspirin therapy.
Design
  • Multicenter, double blind, randomized, placebo-controlled trial
  • 3,491 patients, aged 18 to 75 years of age, within 12 hours after the onset of an ST-elevation myocardial infarction.
  • Patients were scheduled to undergo angiography 48-192 hours after the initiation of study medication.
Exclusion Criteria
None.
Follow-Up
30 days
Treatment Regimen
  • Clopidogrel 300 mg loading dose, then 75 mg once daily versus placebo up to and including day of angiography (or if no angiography, up to and including day 8 or hospital discharge, whichever came first)
  • All patients received a fibrinolytic agent, aspirin, and heparin (if fibrin-specific agent was chosen).
Results
Patients who underwent angiography:

Primary Endpoint: Composite of an occluded infarct-related artery (TIMI flow grade 0 or 1) on angiography, death from any cause before angiography could be performed, or recurrent myocardial infarction before angiography

Patients who did not undergo angiography:

Primary Endpoint: Composite of death or recurrent myocardial infarction by day 8 or hospital discharge, whichever came first.

Primary safety endpoint: Rate of TIMI major bleeding by the end of the day post-angiography or by day 8 or hospital discharge, whichever came first (if angiography not done)

Clopidogrel had significant benefit on all angiographic measurements. Clopidogrel reduced the risk of intracoronary thrombus (43% vs 50.8%; p<0.001).

At 30 days, there was no significant difference in cardiovascular death. Clopidogrel reduced the incidence of ischemic complications, including stroke.

Rates of intracranial hemorrhage and minor bleeding were comparable between the two groups.
Summary
In patients 75 years of age or younger presenting with ST-elevation myocardial infarction and treated with a fibrinolytic and aspirin benefit from the addition of clopidogrel to improve the patency rate of the infarct-related artery to reduce ischemic complications, without increasing bleeding risk.
Implications
None.
Related Figures
[2]