Benefit of clopidogrel in patients with acute coronary syndromes without ST-segment elevation in various risk groups.
BACKGROUND
The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial demonstrated that clopidogrel, given early and continued long term, was superior to placebo in patients with non-ST-elevation acute coronary syndromes receiving aspirin. The purpose of the present analysis was to estimate the treatment effect Zof clopidogrel in patients who were stratified according to their risk of future cardiovascular events.


RESULTS
Patients (n=12 562) who presented within 24 hours after the onset of symptoms were randomized to receive clopidogrel (300 mg followed by 75 mg daily) or placebo in addition to aspirin for 3 to 12 months. Treatment effect was analyzed in various risk groups according to the Thrombolysis in Myocardial Infarction (TIMI) risk score. The TIMI risk model was validated in the CURE population (C statistic, 0.634). The primary composite outcome of cardiovascular death, myocardial infarction, or stroke increased proportionally with increasing risk according to the TIMI risk score. The impact of clopidogrel versus placebo on the rate of the primary outcome was as follows: low-risk group (TIMI score 0 to 2), 4.1% versus 5.7% (relative risk [RR], 0.71; 95% confidence interval [CI], 0.52 to 0.97; P< 0.04), intermediate-risk group (TIMI score 3 to 4), 9.8% versus 11.4% (RR, 0.85; 95% CI, 0.74 to 0.98; P<0.03), and high-risk group (TIMI score 5 to 7), 15.9% versus 20.7% (RR, 0.73; 95% CI, 0.60 to 0.90; P<0.004). There was no evidence of statistical heterogeneity among the groups.


CONCLUSIONS
The benefit of clopidogrel demonstrated in the CURE trial is consistent in low-, intermediate-, and high-risk patients with acute coronary syndromes (as stratified by TIMI risk score), thus supporting its use in all patients with documented non-ST elevation acute coronary syndromes.
Budaj
Andrzej
A
Postgraduate Medical School, Grochowski Hospital Warsaw, Poland.
Yusuf
Salim
S
Mehta
Shamir R
SR
Fox
Keith A A
KA
Tognoni
Gianni
G
Zhao
Feng
F
Chrolavicius
Susan
S
Hunt
David
D
Keltai
Matyas
M
Franzosi
Maria Grazia
MG
D000208:Acute Disease; D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D000077144:Clopidogrel; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin