Design and rationale of Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 trial.

BACKGROUND: Although fibrinolysis is effective in improving outcomes in ST-elevation myocardial infarction (STEMI), failure to achieve reperfusion and/or reocclusion of the infarct-related artery occur in substantial proportions of patients during their index hospitalization and are associated with a significant increase in mortality. We hypothesize that the addition of clopidogrel to standard fibrinolytic therapy in patients with acute STEMI will improve reperfusion.

STUDY DESIGN: CLARITY-TIMI 28 is a multicenter, international, randomized, double-blind, placebo-controlled trial designed to examine the efficacy and safety of clopidogrel when added to standard adjuvant therapy for fibrinolysis. The primary efficacy end point is the composite of an occluded infarct-related artery (defined as TIMI flow grade 0 or 1) on the predischarge angiogram or death or a recurrent myocardial infarction (MI) up to the start of coronary angiography. For subjects who do not undergo angiography, occurrence of death or recurrent MI by day 8 or by hospital discharge, whichever comes first, is used. The primary safety assessment is TIMI major bleeding. Secondary end points include ST resolution at 180 minutes and the clinical composite of death, MI, or recurrent ischemia. Substudies include analyses of biomarkers, DNA, continuous electrocardiogram monitoring, and initiation of treatment in the ambulance.

CONCLUSIONS: CLARITY-TIMI 28 will help to define the role of clopidogrel as part of the pharmacologic reperfusion regimen for acute STEMI.