Aspirin Efficacy in Primary Prevention: A Meta-analysis of Randomized Controlled Trials
The role of aspirin as a means of primary prevention remains controversial.
We have conducted a meta-analysis of all randomized controlled trials (RCTs) to evaluate the role of aspirin in primary prevention.
Literature search was performed via PubMed, Embase, and the Cochrane Library for all related RCTs. All-cause mortality was the primary endpoint. Secondary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular mortality, cerebrovascular events, and bleeding events. We used a random effects model to report the risk ratios (RRs) with 95% confidence intervals (CIs).
Our analysis included 17 RCTs (164,862 patients; 83,309 received aspirin and 81,744 received placebo). Our study did not demonstrate any significant reduction in all-cause mortality for patients treated with aspirin when compared with placebo (RR 0.97; 95% CI 0.93–1.01; P = 0.13). Sensitivity analysis performed by excluding healthy elderly (≥ 65) showed significant reductions in all-cause mortality in the aspirin-treated patients (RR 0.94; 95% CI 0.90–0.99; P = 0.01). There were no significant differences between both groups regarding cardiovascular mortality and cerebrovascular events (P > 0.05). However, aspirin-treated patients significantly reduced MACE and MI events (RR 0.89; 95% CI 0.85–0.93; P < 0.001 and RR 0.88; 95% CI 0.78–0.98; P = 0.02, respectively), respectively. However, aspirin was associated with a significantly higher incidence of bleeding, including major bleeding and intracranial bleeding (P < 0.001).
Aspirin use in primary prevention has resulted in a lower incidence of MACE and MI without significantly effecting cerebrovascular events. However, aspirin was associated with a higher bleeding risk. Use of aspirin as a means of primary prevention should be thoroughly discussed with patients and pursued based on the risk of cardiovascular disease while also considering bleeding risk.
KeywordsAspirin Primary prevention Meta-analysis Cardiovascular disease
MB: study design, data extraction, data analysis, manuscript drafting, and final approval; BK: study design, data extraction, data analysis, manuscript drafting, and final approval; YZ: data search, data extraction, analysis, and final approval; IG: data search, data extraction, and final approval; AA: data extraction, data analysis, and final approval; OB: study design, manuscript drafting, and final approval; LR: data analysis, figure creation, and final approval; GB: data interpretation, manuscript revising, and final approval; MLA: data interpretation, manuscript revising, and final approval.
Compliance with Ethical Standards
Conflict of interest
The authors report no relationships that could be construed as a conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 7.Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, 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;337:a1840.CrossRefGoogle Scholar
- 10.Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018.Google Scholar
- 12.Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet (London, England). 2018;392:1036–46.CrossRefGoogle Scholar
- 14.Goicoechea M, de Vinuesa SG, Quiroga B, Verde E, Bernis C, Morales E, et al. Aspirin for primary prevention of cardiovascular disease and renal disease progression in chronic kidney disease patients: a multicenter randomized clinical trial (AASER Study). Cardiovasc Drugs Ther. 2018;32:255–63.CrossRefGoogle Scholar
- 18.Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, HOT Study Group, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. Lancet (London, England). 1998;351:1755–62.CrossRefGoogle Scholar
- 19.Final report on the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med. 1989;321:129–35.Google Scholar
- 22.The Medical Research Council’s General Practice Research. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet (London, England). 1998;351:233–41.CrossRefGoogle Scholar
- 23.Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representation. Eur Heart J. 2016;37:2315–81.CrossRefGoogle Scholar
- 26.Ebell MH. USPSTF recommendations: new and updated in 2016. Am Fam Phys. 2017;96:697–8.Google Scholar