Clinical research study
Effect of Aspirin on Mortality in the Primary Prevention of Cardiovascular Disease

https://doi.org/10.1016/j.amjmed.2011.01.018Get rights and content

Abstract

Objective

The lack of a mortality benefit of aspirin in prior meta-analyses of primary prevention trials of cardiovascular disease has contributed to uncertainty about the balance of benefits and risks of aspirin in primary prevention. We performed an updated meta-analysis of randomized controlled trials of aspirin to obtain best estimates of the effect of aspirin on mortality in primary prevention.

Methods

Eligible articles were identified by searches of electronic databases and reference lists. Outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and bleeding. Data were pooled from individual trials using the DerSimonian-Laird random-effects model, and results are presented as relative risk (RR) and 95% confidence intervals (CIs).

Results

Nine randomized controlled trials enrolling 100,076 participants were included. Aspirin reduced all-cause mortality (RR 0.94; 95% CI, 0.88-1.00), myocardial infarction (RR 0.83; 95% CI, 0.69-1.00), ischemic stroke (RR 0.86; 95% CI, 0.75-0.98), and the composite of myocardial infarction, stroke, or cardiovascular death (RR 0.88; 95% CI, 0.83-0.94), but did not reduce cardiovascular mortality (RR 0.96; 95% CI, 0.84-1.09). Aspirin increased the risk of hemorrhagic stroke (RR 1.36; 95% CI, 1.01-1.82), major bleeding (RR 1.66; 95% CI, 1.41-1.95), and gastrointestinal bleeding (RR 1.37; 95% CI, 1.15-1.62). A lack of availability of patient-level data precluded exploration of benefits and risks of aspirin in key subgroups.

Conclusion

Aspirin prevents deaths, myocardial infarction, and ischemic stroke, and increases hemorrhagic stroke and major bleeding when used in the primary prevention of cardiovascular disease.

Section snippets

Materials and Methods

We adopted the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for the reporting of this meta-analysis.20, 21 A protocol was prospectively developed detailing the study objectives, primary and secondary outcomes, criteria for study selection, approach to assessing study quality, data synthesis, and statistical analyses.

Study Selection

The process of study selection is outlined in Figure 1. Reviewer agreement at the level of study selection from full text articles as assessed by Cohen's unweighted kappa was 0.86 (standard error 0.14).

Study Characteristics

Nine studies involving 100,076 participants were included. Study and participant characteristics are summarized in Table 1. Three of the nine studies, the British Doctors Trial (BDT),23 Physicians' Health Study (PHS),24 and Thrombosis Prevention Trial (TPT),25 did not include women, whereas the

Discussion

Our meta-analysis of 9 aspirin primary prevention trials involving 100,076 patients demonstrates that long-term aspirin compared with placebo or no aspirin reduces all-cause mortality, myocardial infarction, and ischemic stroke; does not reduce cardiovascular mortality; and increases hemorrhagic stroke, major bleeding, and gastrointestinal bleeding.

In the absence of a mortality benefit of aspirin, treatment guidelines for the use of aspirin for primary prevention of cardiovascular disease have

Conclusions

Our results demonstrate a consistent pattern of reduced mortality in all of the aspirin primary prevention trials and a significant, albeit modest, reduction in all-cause mortality when the data are pooled. This reduction in all-cause mortality tilts the balance between the benefits and risks of treatment in favor of the use of aspirin. The results of our meta-analysis are in agreement with those of the 2009 Antithrombotic Trialists' Collaboration meta-analysis in secondary prevention and

References (36)

  • J.S. Berger et al.

    Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials

    JAMA

    (2006)
  • C. Baigent et al.

    Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials

    Lancet

    (2009)
  • T.A. Pearson et al.

    AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular DiseasesAmerican Heart Association Science Advisory and Coordinating Committee

    Circulation

    (2002)
  • J.B. Buse et al.

    Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association

    Circulation

    (2007)
  • I. Graham et al.

    European guidelines on cardiovascular disease prevention in clinical practice: executive summaryFourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts)

    Eur J Cardiovasc Prev Rehabil

    (2007)
  • Aspirin for the prevention of cardiovascular diseaseU.S. Preventive Services Task Force recommendation statement

    Ann Intern Med

    (2009)
  • JBS 2Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice

    Heart

    (2005)
  • J. Belch et al.

    The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease

    BMJ

    (2008)
  • Cited by (0)

    Funding: None.

    Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.

    Authorship: All authors had access to the data and played a role in writing this manuscript.

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