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Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease
Alessandro Squizzato1, Tymen Keller, Erica Romualdi
1Research Center on Thromboembolic Disorders and Antithrombotic Therapies, Department of Clinical Medicine, University of Insubria, Medicina 1, viale Borri, 57, Varese, Italy, 21100.
Insights
Adding clopidogrel to aspirin reduces cardiovascular events but increases major bleeding risk. Benefits outweigh harms only in patients with acute non-ST coronary syndrome.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Aspirin is a standard prophylactic antiplatelet therapy for cardiovascular disease.
- Combining aspirin with a second antiplatelet, like clopidogrel, may enhance protection for high-risk individuals.
Purpose of the Study:
- To evaluate the benefits and harms of adding clopidogrel to long-term aspirin therapy.
- To assess the impact on preventing cardiovascular events in high-risk and established cardiovascular disease patients.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) comparing aspirin plus clopidogrel versus aspirin alone or with placebo.
- Searches updated through CENTRAL, MEDLINE, and EMBASE up to September 2009.
- Data extraction included cardiovascular events, mortality, and bleeding complications; pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.
Main Results:
- Two RCTs (CURE and CHARISMA) were included. Clopidogrel plus aspirin reduced cardiovascular events (OR: 0.87, 95% CI 0.81-0.94) but increased major bleeding (OR: 1.34, 95% CI 1.14-1.57).
- For every 1000 patients treated, 13 cardiovascular events were prevented, but 6 major bleeds occurred.
- In the CURE trial (acute coronary syndrome), 23 events were avoided and 10 major bleeds occurred per 1000 patients. In CHARISMA, 5 events were avoided and 3 bleeds occurred.
Conclusions:
- Clopidogrel combined with aspirin reduces cardiovascular event risk and increases bleeding risk compared to aspirin alone.
- The benefits of dual antiplatelet therapy outweigh the harms primarily in patients with acute non-ST segment elevation myocardial infarction.
Background:
Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for those at high risk and those with established cardiovascular disease.
Objectives:
To quantify the benefit and harm of adding clopidogrel to standard long-term aspirin therapy for preventing cardiovascular events in people at high risk of cardiovascular disease and those with established cardiovascular disease.
Search Strategy:
The searches have been updated: CENTRAL (Issue 3 2009), MEDLINE (2002 to September 2009) and EMBASE (2002 to September 2009).
Selection Criteria:
All randomized controlled trials comparing long term use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in patients with coronary disease, ischemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease were included.
Data Collection And Analysis:
Data on mortality, non-fatal myocardial infarction, non-fatal stroke, unstable angina, heart failure, revascularizations, major and minor bleeding, and all adverse events were collected. The overall treatment effect was estimated by the pooled odds ratio (OR) with 95% confidence interval (CI) using a fixed-effect model (Mantel-Haenszel).
Main Results:
No new studies were identified from the updated searches. A total of two RCTs were found: the CHARISMA and the CURE study. The CURE study enrolled only patients with a recent non-ST segment elevation acute coronary syndrome. The use of clopidogrel plus aspirin, compared with placebo plus aspirin, was associated with a lower risk of cardiovascular events (OR: 0.87, 95% CI 0.81 to 0.94; P<0.01) and a higher risk of major bleeding (OR 1.34, 95% CI 1.14 to 1.57; P<0.01). Overall, we would expect 13 cardiovascular events to be prevented for every 1000 patients treated with the combination, but 6 major bleeds would be caused. In the CURE trial, for every 1000 people treated, 23 events would be avoided and 10 major bleeds would be caused. In the CHARISMA trial, for every 1000 people treated, 5 cardiovascular events would be avoided and 3 major bleeds would be caused.
Authors' Conclusions:
The available evidence demonstrates that the use of clopidogrel plus aspirin is associated with a reduction in the risk of cardiovascular events and an increased risk of bleeding compared with aspirin alone. Only in patients with acute non-ST coronary syndrome benefits outweigh harms.
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