Effect of addition of clopidogrel to aspirin on mortality: systematic review of randomized trials.

Background and Purpose—In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, addition of clopidogrel to aspirin was associated with an unexpected increase in mortality in patients with lacunar strokes. We assessed the effect of the addition of clopidogrel to aspirin on mortality in a meta-analysis of published randomized trials. Methods—Randomized trials in which clopidogrel was added to aspirin in subjects with vascular disease or vascular risk factors were identified. Trials were restricted to those with a mean follow-up of ≥14 days in which both the combination of aspirin and clopidogrel was tested and mortality was reported. Results—Twelve trials included 90 934 participants (mean age, 63 years; 70% men; median follow-up, 1 year) with 6849 observed deaths. There was no significant increase in mortality with the combination therapy either in 4 short-term (14 days–3 months; OR, 0.93; 95% CI, 0.87–0.99) or in 7 long-term (>3 months; hazard ratio, 0.97; 95% CI, 0.91–1.04) trials after 1 l...