The role of clopidogrel in early and sustained arterial patency after fibrinolysis for ST-segment elevation myocardial infarction: the ECG CLARITY-TIMI 28 Study.
OBJECTIVE
This study was designed to determine the relationship between clopidogrel and early ST-segment resolution (STRes) and the interaction of the two with clinical outcomes after fibrinolysis.


BACKGROUND
ST-segment resolution is an early noninvasive marker of coronary reperfusion.


METHODS
The CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28) trial randomized 3,491 patients with ST-segment elevation myocardial infarction (STEMI) undergoing fibrinolysis to clopidogrel versus placebo. ST-segment resolution was defined as complete (>70%), partial (30% to 70%), or none (<30%).


RESULTS
Electrocardiograms were valid for interpretation in 2,431 patients at 90 min and 2,087 at 180 min. There was no difference in the rate of complete STRes between the clopidogrel and placebo groups at 90 min (38.4% vs. 36.6% at 90 min). When patients were stratified by STRes category, treatment with clopidogrel resulted in greater benefit among those with evidence of early STRes, with greater odds of an open artery at late angiography in patients with partial (odds ratio [OR] 1.4, p = 0.04) or complete (OR 2.0, p < 0.001) STRes, but no improvement in those with no STRes at 90 min (OR 0.89, p = 0.48) (p for interaction = 0.003). Clopidogrel was also associated with a significant reduction in the odds of an in-hospital death or myocardial infarction in patients who achieved partial (OR 0.30, p = 0.003) or complete STRes at 90 min (OR 0.49, p = 0.056), whereas clinical benefit was not apparent in patients who had no STRes (OR 0.98, p = 0.95) (p for interaction = 0.027). By 30 days, the clinical benefit of clopidogrel was predominately seen in patients with complete STRes.


CONCLUSIONS
Clopidogrel appears to improve late coronary patency and clinical outcomes by preventing reocclusion of open arteries rather than by facilitating early reperfusion.
Scirica
Benjamin M
BM
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. bscirica@partners.org
Sabatine
Marc S
MS
Morrow
David A
DA
Gibson
C Michael
CM
Murphy
Sabina A
SA
Wiviott
Stephen D
SD
Giugliano
Robert P
RP
McCabe
Carolyn H
CH
Cannon
Christopher P
CP
Braunwald
Eugene
E
D000368:Aged; D000077144:Clopidogrel; D003326:Coronary Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D015996:Survival Rate; D015912:Thrombolytic Therapy; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine