Twelve studies (23,814 participants) were included in the review. Nine were RCTs (19,995 participants) and three were observational studies (3,819 participants). Sample sizes ranged from 40 to 17,263 and follow-up from 30 to 180 days. The methodological quality of studies was considered high with nine studies meeting at least three of the four quality measures. All studies defined the inception cohort. Loss to follow-up of less than 10% was reported in nine studies, as was blinded outcome assessment. However, seven studies did not clearly report whether patient enrolment was selective.
Major adverse cardiac and/or cerebrovascular events were significantly reduced by a 150mg dose of clopidogrel compared to a 75mg dose (3.89% versus 5.07%; OR 0.67, 95% CI 0.48 to 0.94; eight trials). There were also significant reductions in the individual outcomes myocardial infarction, target revascularization, and stent thrombosis, though not cardiovascular death.
A dose of 150mg/day significantly increased total bleeding complications (6.96% versus 6.20%; OR 1.21, 95% CI 1.09 to 1.34; eight trials). Minor bleeding also showed a statistically significant increase with the higher dose; major bleeding was also increased but not statistically.
Adenosine diphosphate-induced maximal platelet aggregation was also reported; both 20μM (three trials) and 5μM (three trials) were significantly lower with a clopidogrel dose of 150mg/day.
Results of subgroup analyses and a sensitivity analysis without the largest trial were reported. There was evidence of interactions between co-administration of statins, proton-pump inhibitors and GP IIb-IIIa inhibitors and clopidogrel dose. Details of these were reported.
There was evidence of possible publication bias for the outcome of cardiovascular death.