Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial.
BACKGROUND
Antiplatelet therapy and antithrombin therapy have been demonstrated to reduce the risk of cardiac events in patients presenting with acute coronary syndrome, yet all effective therapies also increase the risk of bleeding.


RESULTS
In the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) trial, 12 562 patients were randomized to clopidogrel or placebo in addition to aspirin, and the primary outcome was cardiovascular (CV) death, myocardial infarction (MI), or stroke. The benefits were consistent among those undergoing percutaneous coronary intervention (PCI) [9.6% for clopidogrel, 13.2% for placebo; relative risk (RR), 0.72; 95% CI, 0.57 to 0.90], coronary artery bypass grafting (CABG) surgery (14.5% for clopidogrel 16.2% for placebo; RR, 0.89; 95% CI, 0.71 to 1.11), and medical therapy only (8.1% for clopidogrel, 10.0% for placebo; RR, 0.80; 95% CI, 0.69 to 0.92; test for interaction among strata, 0.53). For CABG during the initial hospitalization (530 for placebo, 485 for clopidogrel), the frequency of CV death, MI or stroke before CABG was 4.7% for placebo and 2.9% for clopidogrel (RR, 0.56; 95% CI, 0.29 to 1.08). For the entire study, there was a 1% excess of major bleeding but no significant excess of life-threatening bleeding. Among patients undergoing CABG, the rates of life-threatening bleeding were 5.6% for clopidogrel and 4.2% for placebo (RR, 1.30; 95% CI, 0.91 to 1.95; both nonsignificant).


CONCLUSIONS
The benefits versus risks of early and long-term clopidogrel therapy (freedom from CV death, MI, stroke, or life-threatening bleeding) are similar in those undergoing revascularization (CABG or PCI) and in the study population as a whole. Overall, the benefits of starting clopidogrel on admission appear to outweigh the risks, even among those who proceed to CABG during the initial hospitalization.
Fox
Keith A A
KA
Royal Infirmary of Edinburgh, Edinburgh, UK. k.a.a.fox@ed.ac.uk
Mehta
Shamir R
SR
Peters
Ron
R
Zhao
Feng
F
Lakkis
Nasser
N
Gersh
Bernard J
BJ
Yusuf
Salim
S
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000150:complications; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000503:physiopathology / Q000601:surgery* / Q000628:therapy; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D020521:Stroke / Q000453:epidemiology; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin