The relative efficacy and safety of clopidogrel in women and men a sex-specific collaborative meta-analysis.
OBJECTIVE
This study sought to investigate the efficacy and safety of clopidogrel in women and men.


BACKGROUND
Previous analyses have shown sex-based differences in response to several antiplatelet medications. Little is known about the efficacy and safety of clopidogrel in women and men.


METHODS
This study performed a meta-analysis of all blinded randomized clinical trials comparing clopidogrel and placebo (CURE [Clopidogrel in Unstable Angina to Prevent Recurrent Events], CREDO [Clopidogrel for the Reduction of Events During Observation], CLARITY-TIMI 28 [Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28], COMMIT [Clopidogrel and Metoprolol in Myocardial Infarction Trial], and CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance] trials), involving a total of 79,613 patients, of whom 30% were women. The relative efficacy and safety of clopidogrel at reducing cardiovascular events (cardiovascular death, myocardial infarction [MI], or stroke) in women and men was estimated using random-effects modeling.


RESULTS
Overall, clopidogrel was associated with a highly significant 14% proportional reduction in the risk of cardiovascular events (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93), with no significant differences in treatment effect between women and men. Among the 23,533 women enrolled, there were fewer cardiovascular events in the clopidogrel group compared with the placebo group (11.0% vs. 11.8%; OR: 0.93; 95% CI: 0.86 to 1.01). In women the risk reduction with clopidogrel seemed to be greatest for MI (OR: 0.81; 95% CI: 0.70 to 0.93), with the effects on stroke (OR: 0.91; 95% CI: 0.69 to 1.21) or total death (OR: 0.99; 95% CI: 0.90 to 1.08) not statistically significant. Among the 56,091 men enrolled, there were fewer cardiovascular events in those receiving clopidogrel compared with placebo (7.8% vs. 9.0%; OR: 0.84; 95% CI: 0.78 to 0.91), and the risk reduction was significant for MI (OR: 0.83; 95% CI: 0.76 to 0.92), stroke (OR: 0.83; 95% CI: 0.71 to 0.96), and total death (OR: 0.91; 95% CI: 0.84 to 0.97). Clopidogrel increased the risk of major bleeding in both women (OR: 1.43; 95% CI: 1.15 to 1.79) and men (OR: 1.22; 95% CI: 1.05 to 1.42).


CONCLUSIONS
Clopidogrel reduces the risk of cardiovascular events in both women and men.
Berger
Jeffrey S
JS
New York University School of Medicine, New York, New York, USA. jeffrey.berger@nyumc.org
Bhatt
Deepak L
DL
Cannon
Christopher P
CP
Chen
Zhengming
Z
Jiang
Lixin
L
Jones
James B
JB
Mehta
Shamir R
SR
Sabatine
Marc S
MS
Steinhubl
Steven R
SR
Topol
Eric J
EJ
Berger
Peter B
PB
D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D015995:Prevalence; D055502:Secondary Prevention; D017678:Sex Distribution; D012737:Sex Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine