Aspirin has potential benefits for primary prevention of cardiovascular outcomes in diabetes: updated literature-based and individual participant data meta-analyses of randomized controlled trials

Abstract

Background The clinical benefit of aspirin for the primary prevention of cardiovascular disease (CVD) in diabetes remains uncertain. To evaluate the efficacy and safety of aspirin for the primary prevention of cardiovascular outcomes and all-cause mortality events in people with diabetes, we conducted an updated meta-analysis of published randomised controlled trials (RCTs) and a pooled analysis of individual participant data (IPD) from three trials. Methods Randomised controlled trials of aspirin compared with placebo (or no treatment) in participants with diabetes with no known CVD were identified from MEDLINE, Embase, Cochrane Library, and manual search of bibliographies to January 2019. Relative risks with 95% confidence intervals were used as the summary measures of associations. Results We included 12 RCTs based on 34,227 participants with a median treatment duration of 5.0 years. Comparing aspirin use with no aspirin, there was a significant reduction in risk of major adverse cardiovascular events (MACE)0.89 (0.83–0.95), with a number needed to treat (NNT)of 95 (95% CI 61 to 208) to prevent one MACE over 5 years average follow-up. Evidence was lacking of heterogeneity and publication bias among contributing trials for MACE. Aspirin use had no effect on other endpoints including all-cause mortality; however, there was a significant reduction in stroke for aspirin dosage ≤ 100 mg/day 0.75 (0.59–0.95). There were no significant effects of aspirin use on major bleeding and other bleeding events, though some of the estimates were imprecise. Pooled IPD from the three trials (2306 participants) showed no significant evidence of an effect of aspirin on any of the outcomes evaluated; however, aspirin reduced the risk of MACE in non-smokers 0.70 (0.51–0.96) with a NNT of 33 (95% CI 20 to 246) to prevent one MACE. Conclusions Aspirin has potential benefits in cardiovascular primary prevention in diabetes. The use of low dose aspirin may need to be individualised and based on each individual’s baseline CVD and bleeding risk. Systematic review registration PROSPERO: CRD42019122326 Electronic supplementary material The online version of this article (10.1186/s12933-019-0875-4) contains supplementary material, which is available to authorized users.

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