Elsevier

American Heart Journal

Volume 162, Issue 1, July 2011, Pages 115-124.e2
American Heart Journal

Clinical Investigation
Prevention and Rehabilitation
Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: A meta-analysis of randomized trials

https://doi.org/10.1016/j.ahj.2011.04.006Get rights and content

Background

The benefit of aspirin to prevent cardiovascular events in subjects without clinical cardiovascular disease relative to the increased risk of bleeding is uncertain.

Methods

A meta-analysis of randomized trials of aspirin versus placebo/control to assess the effect of aspirin on major cardiovascular events (MCEs) (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), individual components of the MCE, stroke subtype, all-cause mortality, and major bleeding. Nine trials involving 102,621 patients were included: 52,145 allocated to aspirin and 50,476 to placebo/control.

Results

Over a mean follow-up of 6.9 years, aspirin was associated with a reduction in MCE (risk ratio [RR] 0.90, 95% CI 0.85-0.96, P < .001). There was no significant reduction for myocardial infarction, stroke, ischemic stroke, or all-cause mortality. Aspirin was associated with hemorrhagic stroke (RR 1.35, 95% CI 1.01-1.81, P = .04) and major bleeding (RR 1.62, 95% CI 1.31-2.00, P < .001). In meta-regression, the benefits and bleeding risks of aspirin were independent of baseline cardiovascular risk, background therapy, age, sex, and aspirin dose. The number needed to treat to prevent 1 MCE over a mean follow-up of 6.9 years was 253 (95% CI 163-568), which was offset by the number needed to harm to cause 1 major bleed of 261 (95% CI 182-476).

Conclusions

The current totality of evidence provides only modest support for a benefit of aspirin in patients without clinical cardiovascular disease, which is offset by its risk. For every 1,000 subjects treated with aspirin over a 5-year period, aspirin would prevent 2.9 MCE and cause 2.8 major bleeds.

Section snippets

Search strategy

From 1966 to 2005, a computerized search was performed that identified 6 published randomized trials of aspirin in patients without clinical CVD. In the previous meta-analysis of these trials, aspirin therapy significantly reduced the risk of an MCE (nonfatal MI, nonfatal stroke, or cardiovascular death) by 12% in women and 14% in men.18 From 2005 to the present, a subsequent review of the literature (MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE) identified 3

Results

Nine prospective randomized trials involving 102,621 participants were identified for inclusion. A total of 710,053 person-years of exposure were recorded: 359,709 in the aspirin group and 350,344 in the placebo or control group. All trials included patients without clinical CVD, which was defined as the absence of a cardiovascular event, or clinical symptoms of CVD including angina or transient ischemic attack. Among the 3 new trials,19, 20, 21 2 included only diabetic patients,19, 21 and 2

Discussion

The current meta-analysis included 9 prevention trials in >100,000 subjects without clinical evidence of CVD treated with aspirin versus placebo or control for the prevention of ischemic cardiovascular events. The pooled results found a statistically significant 10% relative reduction in the primary end point of MCE and a statistically significant 62% relative increase in major bleeding events. The absolute benefit versus risk demonstrated that, in 1,000 patients treated for 5 years, there were

Conclusions

This meta-analysis of >100,000 randomized patients (>700,000 person-year follow-up) comparing aspirin versus placebo or control demonstrated that aspirin decreased MCE by approximately 10% among patients without clinical CVD. Major bleeding, however, occurred more frequently with aspirin therapy. The decision to use aspirin for the prevention of a first MI or stroke remains a complex issue. Weighing the overall benefit and risk requires careful consideration by the physician and patient before

Disclosures

Dr Jeffrey Berger reports receiving research support from Astra Zaneca and has received honoraria for advisory board participation from Astra Zaneca. Dr William Hiatt reports receiving research support from Astra Zaneca.

Conflicts of interest: none. Drs Berger and Hiatt had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Acknowledgements

We thank Dr Sanjay Kaul for his insightful comments and editorial assistance.

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    Roger S. Blumenthal, MD served as guest editor for this article.

    Dr Berger was partially funded by an American Heart Association Fellow to Faculty Award (0775074N). Dr Krantz was partially funded by grant U01 HL079160 from the National Heart, Lung, and Blood Institute.

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