Clopidogrel monotherapy is superior to aspirin monotherapy for prevention of major adverse cardiovascular or cerebrovascular events (MACCE) without increasing major bleeding risk and supports the use of clopidogrel over aspirin for secondary prevention in patients with coronary artery disease (CAD), according to a systematic review and meta-analysis published Aug. 31 in The Lancet.

Marco Valgimigli, MD, et al., examined outcomes in 28,982 patients with established CAD (14,507 assigned to clopidogrel; 14,475 assigned to aspirin) who had discontinued or never started dual antiplatelet therapy from seven randomized trials (ASCET, CADET, CAPRIE, HOST-EXAM, STOPDAPT-2, STOPDAPT-3 and SMART-CHOICE). Their mean age was 66 years and 22% were men.

In this individual patient level analysis, results revealed that MACCE was approximately 14% less likely in patients receiving clopidogrel vs. aspirin (929 events [2.61 per 100 patient-years] vs. 1,062 events [2.99 per 100 patient-years]; p=0.0082) at the longest follow-up of 5.5 years. Notably, the relative risk reduction in MACCE observed with clopidogrel vs. aspirin was primarily driven by the approximate 20% reduction in myocardial infarction and stroke events.

Findings also showed no difference in major bleeding, any bleeding or gastrointestinal bleeding (256 events [0.71 per 100 patient-years] with clopidogrel vs. 279 events [0.77 per 100 patient-years] with aspirin; hazard ratio, 0.94; p=0.64). Additionally, no difference in all-cause or cardiovascular mortality was observed between groups.

In other findings, treatment effects were consistent across subgroups. Even patients with impaired responsiveness to clopidogrel because of genetic or clinical factors still benefited from its use over aspirin.

Although both clopidogrel and aspirin are available as generic medications, clopidogrel may cost incrementally more in many countries, the researchers note. Thus, cost-effectiveness studies "are needed to better inform clinical and policy decisions."

Valgimigli and colleagues write the overall study results "support the consideration of clopidogrel as the preferred long-term antiplatelet strategy instead of aspirin in patients with established CAD."