Outcome comparison of 600 mg versus 300 mg loading dose of clopidogrel for patients with ST-elevation myocardial infarction: a meta-analysis.

Background: A 600-mg loading dose (LD) of clopidogrel has been shown to be superior to a 300-mg LD in inhibiting platelet function. However, data for clinical superiority are limited, and there is a paucity of adequately powered randomized trials investigating this issue. This meta-analysis was performed to determine the optimal LD of clopidogrel in ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

Methods: A meta-analysis of controlled trials and observational studies was performed comparing 600-mg with 300-mg LDs of clopidogrel. The primary efficacy end point was a major adverse cardiac event (MACE), and the primary safety end point was major bleeding. Data were extracted on an intention to treat basis. The X2 test was used to evaluate heterogeneity. A random effects model was used, and odds ratios (OR) were calculated using the Mantel-Haenszel method.

Results: Nine studies involving 18 623 patients were included in the efficacy analysis. Mean duration of follow-up was 8 months. Four studies were eligible for the safety analysis. The MACE risk was lower with a 600-mg LD (7.0% [650/9231]) than with a 300-mg LD (9.2% [867/9392]; OR, 0.75; 95% CI, 0.63-0.91). On the other hand, there was no significant difference in the major bleeding events between the 2 groups (2.5% [89/3551] with 600 mg vs 2.3% [63/2796] with 300 mg; OR, 0.84; 95% CI, (0.60-1.16).

Conclusions: In ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention, administration of a 600-mg LD of clopidogrel is associated with a lower risk of MACE than is administration of a 300-mg LD, without increasing the risk of major bleeding.