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

Study Questions:

What is the association of clopidogrel pretreatment versus no treatment with mortality and major bleeding after percutaneous coronary intervention (PCI)?


Studies reporting clinical data on mortality and major bleeding were included in the analysis. Of the 392 titles identified, 15 articles published between August 2001 and September 2012 met the inclusion criteria: six randomized controlled trials (RCTs), two observational analyses of RCTs, and seven observational studies. The quality of studies was assessed with the Ottawa Scale and the Jadad Score as appropriate. Two reviewers independently extracted results. 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 endpoints were all-cause mortality and major bleeding. Secondary endpoints included major cardiac events.


Of the 37,814 patients included in the meta-analysis, 8,608 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%; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.57-1.11; p = 0.17), 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 < 0.001). 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 = 0.18). Analyses from observational analyses of RCTs and observational studies were consistent for all results.


The authors concluded that 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.


The current meta-analysis collected information in a population of more than 37,000 patients and found no significant association between clopidogrel pretreatment and survival, or between clopidogrel pretreatment and major bleeding. This meta-analysis, however, demonstrated a significant association between clopidogrel pretreatment and the reduction of major coronary events in the primary RCT analyses combining all types of patients, with fully consistent results obtained from observational studies. Whether pretreatment with newer and more potent antiplatelet agents improves survival needs to be assessed in large prospective studies.

Keywords: Platelet Aggregation Inhibitors, Catheterization, Angioplasty, Percutaneous Coronary Intervention

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