Meta-Analysis of the Efficacy and Safety of Clopidogrel Plus Aspirin as Compared to Antiplatelet Monotherapy for the Prevention of Vascular Events

doi:10.1016/j.amjcard.2007.11.057

The American Journal of Cardiology

Volume 101, Issue 7, 1 April 2008, Pages 960-966

https://doi.org/10.1016/j.amjcard.2007.11.057 Get rights and content

Antiplatelet agents are central to the treatment and prevention of cardiovascular disease. Although aspirin is the most widely used agent, randomized trials have assessed whether adding clopidogrel to aspirin (“dual-antiplatelet therapy”) offers additional benefit with acceptable safety. Unfortunately, these trials have reached conflicting results, in part because of the heterogenous populations they studied. To clarify the role of dual-antiplatelet therapy for patients with vascular disease, a systematic review and meta-analysis of randomized controlled trials was performed. Medline and the Cochrane Collaboration and American College of Physicians Journal Club databases were searched for trials published from 1966 to August 2006 that compared aspirin and clopidogrel with antiplatelet monotherapy. Only trials that presented clinically relevant efficacy and safety outcomes were included. From each trial, demographic data and outcomes were recorded. Summary odds ratios and 95% confidence intervals (CIs) were calculated using a random-effects model. Eight trials comprising 91,744 patients were included. Mean follow-up ranged from 28 days to 18 months. Compared with aspirin alone, dual therapy with aspirin and clopidogrel reduced the odds ratio of the composite outcome of death, reinfarction, and stroke by 15% (95% CI 23% to 6%) in patients with acute coronary syndromes and by 34% (95% CI 44% to 22%) in patients who underwent percutaneous coronary intervention. Dual therapy also significantly reduced the odds of fatal and nonfatal reinfarction in these patient groups but did not significantly reduce the odds of all-cause mortality. Dual therapy was associated with significantly increased risk for major bleeding in studies >1 month in duration (odds ratio 1.80, 95% CI 1.40 to 2.30). In conclusion, combining aspirin and clopidogrel significantly reduces the odds of major cardiovascular events in patients with acute coronary syndromes or those who undergo percutaneous coronary intervention but at the expense of significant increases in the risk for bleeding.

Section snippets

Methods

We performed an electronic search of Medline (1966 to August 2006); the Cochrane Collaboration’s Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Cochrane Database of Systematic Reviews; and the American College of Physicians Journal Club database using medical subject headings and keywords related to aspirin and clopidogrel, cardiovascular disease (i.e., “unstable angina,” “ACS,” “myocardial infarction,” “stroke,” “percutaneous coronary intervention,” and

Results

Our search identified 370 reports, of which 8 reported on trials that met our inclusion criteria (Figure 1). Three studies each assessed patients with ACS and those who underwent PCI. The other 2 studies evaluated patients with recent ischemic strokes or transient ischemic attacks⁷ and those with established vascular disease or multiple atherothrombotic risk factors.⁸ All trials compared combined clopidogrel and aspirin with aspirin monotherapy, with the exception of the MATCH trial,⁷ which

Discussion

This meta-analysis of randomized controlled trials demonstrates that the use of clopidogrel in combination with aspirin for patients with ACS or those who undergo PCI significantly reduces the odds of major coronary events and fatal or nonfatal MI, compared with aspirin alone. In contrast, dual-antiplatelet therapy does not reduce the odds of all-cause mortality in these patients, is not superior to antiplatelet monotherapy for patients with subacute vascular disease or recent stroke, and when

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Coronary artery diseaseMeta-Analysis of the Efficacy and Safety of Clopidogrel Plus Aspirin as Compared to Antiplatelet Monotherapy for the Prevention of Vascular Events

Section snippets

Methods

Results

Discussion

Lancet

Lancet

Control Clin Trials

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation

N Engl J Med

Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial

Lancet

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

N Engl J Med

Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial

JAMA

Coronary artery disease
Meta-Analysis of the Efficacy and Safety of Clopidogrel Plus Aspirin as Compared to Antiplatelet Monotherapy for the Prevention of Vascular Events