CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy- Thrombolysis In Myocardial Infarction 28)

18 Mar, 14

Background

A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death.

Prior clopidogrel studies such as CREDO and CURE have been conducted in patients with non-ST elevation acute coronary syndromes.

However, benefits of addition of clopidogrel in patients of MI with ST-segment elevation and receiving fibrinolytic therapy, including aspirin, has not been evaluated.

Aim

To evaluate whether the addition of clopidogrel to standard fibrinolytic therapy, including aspirin, would improve infarct-related artery patency and decrease ischemic complications in patients with ST-segment elevation MI (STEMI).

Study Design

Multicenter, randomized, double-blind, placebo controlled study.

Patient Characteristics

3491 patients, aged 18-75 years, presenting with ischemic discomfort at rest within 12 hours before randomization and which lasted more than 20 minutes; ST-segment elevation of at least 0.1 mV in at least two contiguous limb leads, ST-segment elevation of at least 0.2 mV in at least two contiguous precordial leads, or left bundle-branch block that was not known to be old; and if they were scheduled to receive a fibrinolytic agent, an anticoagulant (if a fibrin-specific lytic agent was prescribed) and aspirin.

Exclusion Criteria

Clopidogrel treatment within 7 days before enrollment or planned treatment with clopidogrel or glycoprotein (GP) IIb/IIIa inhibitors before coronary angiography
Contraindication to thrombolytic therapy
Cardiogenic shock
Prior coronary artery bypass grafting
Intention of angiography with 48 hours in absence of new indication
Received excessive doses of heparin

Study Groups

Group 1: N=1752, randomized to 300-mg loading dose of clopidogrel followed by 75 mg/day
Group 2: N=1739, placebo

Primary Endpoint

Composite of death or recurrent MI or an occluded infarct-related artery (TIMI flow 0 or 1) on angiography.

Results

Clopidogrel significantly reduced the primary composite endpoint by 36%, as compared to placebo

Rate of an occluded infarct-related artery was reduced by 41% with clopidogrel, as compared to placebo

Rate of recurrent MI was reduced by 30% with clopidogrel

Clopidogrel improved all angiographic measurements, including optimal epicardial flow (defined by TIMI flow grade of 3) by 36%, and the odds of achieving optimal myocardial reperfusion (defined by a TIMI myocardial-reperfusion grade of 3) by 21%. The odds of intracoronary thrombus was reduced by 27% with clopidogrel. Clopidogrel also resulted in less severe stenosis and a larger minimal luminal diameter of the infarct-related artery
Clopidogrel reduced the cumulative incidence of the end point of death from cardiovascular causes, recurrent MI, or recurrent ischemia leading to the need for urgent revascularization, by 20%
Major and minor bleeding complication rates were similar in both groups

Conclusion

Addition of clopidogrel to aspirin and a standard fibrinolytic regimen improves the patency rate of the infarct-related artery and reduces ischemic complications in STEMI patients aged 75 years or younger.

Presented at ACC Scientific Sessions, 2005