Association of Clopidogrel Pretreatment With Mortality, Cardiovascular Events, and Major Bleeding Among Patients Undergoing Percutaneous Coronary Intervention A Systematic Review and Meta-analysis

Context Clopidogrel pretreatment is recommended for patients with acute coronary syndromes (ACS) and stable coronary artery disease who are scheduled for percutaneous coronary intervention (PCI), but whether using clopidogrel as a pretreatment for PCI is associated with positive clinical outcomes has not been established. Objective To evaluate the association of clopidogrel pretreatment vs no treatment with mortality and major bleeding after PCI. Data Sources MEDLINE, EMBASE, Cochrane Controlled Trials Register databases, and reference lists of qualifying articles. Study Selection Studies reporting clinical data on mortality and major bleeding were included. Of the 392 titles identified, 15 articles published between August 2001 and September 2012 met the inclusion criteria: 6 randomized controlled trials (RCTs), 2 observational analyses of RCTs, and 7 observational studies. Data Extraction Quality of studies was assessed with the Ottawa Scale and the Jadad Score as appropriate. Results were independently extracted by 2 reviewers. A random-effect model was applied. Pretreatment was defined as the administration of clopidogrel before PCI or catheterization. The main analysis was performed on RCTs and confirmed by observational analyses and observational studies. Prespecified subgroups-clinical presentation and clopidogrel loading dose-were analyzed. The primary efficacy and safety end points were all-cause mortality and major bleeding. Secondary end points included major cardiac events. Results Of the 37 814 patients included in the meta-analysis, 8608 patients had participated in RCTs; 10 945, in observational analyses of RCTs; and 18 261, in observational studies. Analysis of RCTs showed that clopidogrel pretreatment was not associated with a reduction of death (absolute risk, 1.54% vs 1.97%; OR, 0.80; 95% CI, 0.57-1.11; P=.17) but was associated with a lower risk of major cardiac events (9.83% vs 12.35%; OR, 0.77; 95% CI, 0.66-0.89; P<.001). There was no significant association between pretreatment and major bleeding overall (3.57% vs 3.08%; OR, 1.18; 95% CI, 0.93-1.50; P=.18). Analyses from observational analyses of RCTs and observational studies were consistent for all results. Conclusions Among patients scheduled for PCI, clopidogrel pretreatment was not associated with a lower risk of mortality but was associated with a lower risk of major coronary events. JAMA.2012;308(23):2507-2517 www.jama.com