Drug products: Clopidogrel Accord, Clopidogrel Actavis, Clopidogrel Aliud, Clopidogrel Aristo, Clopidogrel Aurobindo, Clopidogrel Krka, Clopidogrel Mylan, Clopidogrel Orion, Clopidogrel Pensa, Clopidogrel ratiopharm, Clopidogrel Sandoz, Clopidogrel STADA, Clopidogrel Teva, Clopidogrel Teva Pharma, Clopidogrel Teva Pharma B.V., Clopidogrel Zentiva, Cloriocard, Grepid, Klopidogrel Arrow, Plavix
ATC code: B01AC04
Substances: clopidogrel, clopidogrel besylate, clopidogrel hydrobromide monohydrate, clopidogrel hydrochloride, clopidogrel hydrogensulphate
Clopidogrel as secondary prevention lowers the risk of cardiovascular disease equally overall in men and women. In men, the risk of myocardial infarction, stroke, and total mortality of cardiovascular disease is decreased while in women the lowered risk of myocardial infarction is more pronounced. In the large COMMIT-study patients with suspected myocardial infarction was treated with clopidogrel or placebo in combination with aspirin. The addition of clopidogrel was found to lower the relative risk of death by all causes and the risk of re-infarction, stroke, or death in a similar way in men and women.
Clopidogrel is a prodrug and it is reported that AUC and Cmax of the active metabolite are similar in healthy adult men and women (79 men, 77 women) .
A large sex-specific meta-analysis (in total 56 091 men, 23 522 women) reports that clopidogrel is effective in reducing cardiovascular events in both men and women. Women achieved cardiovascular benefit mainly by a reduced risk of myocardial infarction (MI), while men had reductions of the risks of suffering MI, stroke and all-cause mortality. Among women, the absolute risk reduction was 0.8% for the composite end point (cardiovascular event, MI, stroke, cardiovascular mortality, all-cause mortality) and 0.7% for MI alone. Among men, the absolute risk reduction was 1.2% for the composite end point and 0.6% for MI . . More recent meta-analyses on P2Y12 inhibitors (prasugrel, ticagrelor, cangrelor) compared to clopidogrel confirms these findings [3, 4].
In the large COMMIT study (in total 45,852, 28% women), which was included in one of the meta-analysis, patients admitted to hospital within 24 h of suspected acute MI onset were randomly allocated clopidogrel 75 mg daily or matching placebo in addition to aspirin 162 mg daily for 4 weeks or until hospital discharge. Clopidogrel reduced the relative risk of death from any cause with 7% and the relative risk of composite outcome of death, re-infarction or stroke with 9%. This benefit was consistent across age and patient’s sex .
Men and women with acute coronary syndrome treated with clopidogrel had similar reduction rates of cardiovascular death, MI or stroke in the PLATO clinical trial, also included in the meta-analyses , in two other clinical trials [7, 8], and a cohort study .
Some studies describe a higher platelet reactivity [10-14] and more clopidogrel resistance in women [15-19], although other studies report no sex differences in platelet response to clopidogrel [20-25]. However, it is unclear whether this is explained by sex differences in pharmacodynamic response to clopidogrel [13, 14, 20, 22] or by a higher baseline pre-treatment platelet activity in women [10, 11]. Furthermore, frequency of clopidogrel resistance may vary between populations.
The risk of major bleeding from clopidogrel treatment was similar in men and women in a large meta-analysis . In a US register-based study in IBS patients (1489 men, 5728 women), treatment with clopidogrel was associated with a higher incidence of GI symptoms in women but not in men .
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2018-11-12
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson