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Effect of Aspirin Dose on Mortality and Cardiovascular Events in People with Diabetes: A Meta-Analysis

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Abstract

Objectives

Pharmacologic evidence suggests adequate antiplatelet activity in diabetic patients requires >100 mg aspirin daily, yet recent trials have used ≤100 mg daily. This meta-analysis explored the relationship between aspirin dose and prevention of cardiovascular events.

Data Sources

Six electronic databases were searched using database-appropriate terms for aspirin, diabetes, and comparative study from inception until February 2010.

Review Methods

Randomized controlled trials and cohort studies comparing aspirin to no antiplatelet therapy were included if they reported cardiovascular events as pre-specified outcomes, aspirin dose, and number of diabetic patients. Studies were stratified by daily aspirin dose (≤100 mg; 101–325 mg; >325 mg) and pooled risk ratios (RR) were calculated using random effects models. All-cause mortality was the primary outcome of interest. Cardiovascular-related mortality, myocardial infarction, and stroke were secondary outcomes.

Results

Data for diabetic patients were available from 21 studies (n = 17,522). Overall, 1,172 (15.4%) of 7,592 aspirin users and 1,520 (18.4%) of 8,269 controls died (p = 0.31). The pooled RRs were 0.89 (95% CI: 0.72–1.10; p = 0.27) from 13 studies using ≤100 mg (I2 = 64%); 0.89 (95% CI: 0.61–1.30; p = 0.55) from four studies using 101–325 mg (I2 = 83%); and 0.96 (95% CI: 0.85–1.08; p = 0.50) from eight studies using >325 mg (I2 = 0%). Aspirin use was associated with a significantly lower risk of mortality (RR: 0.82; 95% CI: 0.69–0.98; p = 0.03) in 13 secondary prevention studies (I2 = 27%), whereas aspirin use in seven primary prevention studies (I2 = 0%) was not (RR: 1.01; 95% CI 0.85–1.19; p = 0.94). A substantial amount of heterogeneity was observed amongst studies in all outcomes. Although inclusion of cohort studies was a major source of heterogeneity, stratification by study design did not reveal a significant dose-response relationship.

Conclusions/Interpretation

This summary of available data does not support an aspirin dose-response effect for prevention of cardiovascular events in diabetic patients. However, the systematic review identified an important gap in randomized controlled trial evidence for using 101–325 mg aspirin daily in diabetes.

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Contributors

We are very grateful for the additional information provided by original study authors.

We thank Angela Adams, Dr. Tomasz Hruczkowski, Dr. Raimar Löbenberg, Dr. Franco Pasutto, and Soleil Surette for their assistance during the article screening phase of our meta-analysis.

We also thank Dr. Sumit Majumdar for providing comments on a draft of this manuscript.

Funding Sources

Dr. Simpson is supported as a New Investigator by the Canadian Institutes of Health Research (CIHR). Mr. Gamble holds a Canada Graduate Scholarship from CIHR and a full-time Health Research Studentship from the Alberta Heritage Foundation for Medical Research (AHFMR).

Prior Presentations

An abstract of this study was presented at the American Diabetes Association Scientific Sessions in June 2010.

Conflict of Interest Disclosure

None disclosed.

Author information

Authors and Affiliations

  1. Faculty of Pharmacy & Pharmaceutical Sciences, 3126 Dentistry / Pharmacy Centre, University of Alberta, Edmonton, AB, Canada, T6G 2N8

    Scot H. Simpson BSP, PharmD, MSc

  2. School of Public Health, University of Alberta, Edmonton, AB, Canada

    John-Michael Gamble BSc(Pharm), MSc

  3. Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada

    Laurie Mereu MD

  4. University of Alberta Library Services, Edmonton, AB, Canada

    Thane Chambers MSc

Authors
  1. Scot H. Simpson BSP, PharmD, MSc
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  2. John-Michael Gamble BSc(Pharm), MSc
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  3. Laurie Mereu MD
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Corresponding author

Correspondence to Scot H. Simpson BSP, PharmD, MSc.

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Simpson, S.H., Gamble, JM., Mereu, L. et al. Effect of Aspirin Dose on Mortality and Cardiovascular Events in People with Diabetes: A Meta-Analysis. J GEN INTERN MED 26, 1336–1344 (2011). https://doi.org/10.1007/s11606-011-1757-y

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