Seven studies (n=25,383 patients) were included in the review, of which five were RCTs. Four RCTs were judged to be at low risk of bias. Follow-up in all trials was 30 days.
Major adverse coronary events: There was a statistically significant lower incidence of major adverse coronary events in patients treated with 600mg loading dose of clopidogrel compared with those receiving 300mg loading dose in the fixed-effect analysis (RR 0.78, 95% CI 0.69 to 0.88; I2=43%) and the random-effects analysis (RR 0.66, 95% CI 0.52 to 0.84; I2=43%). Results of sensitivity analyses were also reported. The test of interaction revealed no impact of study design on treatment effect.
Myocardial infarction and death composite outcome: There was a statistically significant reduction in the composite outcome (RR 0.52, 95% CI 0.29 to 0.99; I2=52%; random-effects model).
Major bleeding events: There was no statistically significant difference between the 600mg and 300mg clopidogrel dose groups for the incidence of major bleeding events (RR 0.91, 95% CI 0.73 to 1.15; I2=0%; random-effects model); this was replicated in the fixed-effect model. Excluding the largest study from the analysis did not change the non-significant result.
The authors stated that the funnel plots were not ideally shaped.