Benefits and Risks Associated with Low-Dose Aspirin Use for the Primary Prevention of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Control Trials and Trial Sequential Analysis.

Background: The role of aspirin in cardiovascular primary prevention remains controversial. Moreover, evidence for the potential benefits of aspirin in patients with high cardiovascular risk remains limited. Objective: The aim of this study was to explore the role of low-dose aspirin in primary prevention. Methods: The PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized clinical trials (RCTs) from the date of inception to August 2021. The efficacy outcomes were major adverse cardiovascular events (MACE), myocardial infarction (MI), ischemic stroke (IS), all-cause mortality, and cardiovascular mortality, whereas safety outcomes were major bleeding, intracranial hemorrhage, and gastrointestinal (GI) bleeding. Subgroup analyses were based on different cardiovascular risks and diabetes statuses. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using the fixed- and random-effects models, and trial sequential analysis (TSA) was conducted to determine the robustness of the results. Results: A total of 10 RCTs fulfilled the inclusion criteria. The use of aspirin was associated with a significant reduction in the risk of MACE (RR 0.89, 95% CI 0.84–0.93), MI (RR 0.86, 95% CI 0.78–0.95), and IS (RR 0.84, 95% CI 0.76–0.93); however, aspirin also increased the risk of safety outcomes, i.e. major bleeding (RR 1.42, 95% CI 1.26–1.60), intracranial hemorrhage (RR 1.33, 95% CI 1.11–1.59), and GI bleeding (RR 1.91, 95% CI 1.44–2.54). Subgroup analyses revealed that in the absence of a statistically significant interaction, a trend toward a net benefit of lower incidence of cardiovascular events (number needed to treat of MACE: high risk: 682 vs. low risk: 2191) and lesser risk of bleeding events (number needed to harm of major bleeding: high risk: 983 vs. low risk: 819) was seen in the subgroup of high cardiovascular risk. Meanwhile, the greater MACE reduction was also detected in the high-risk group of diabetes or nondiabetes patients. Furthermore, a post hoc subgroup analysis indicated a significant rate reduction in patients aged ≤ 70 years but not in patients aged > 70 years. TSA confirmed the benefit of aspirin for MACE up to a relative risk reduction of 10%. Conclusion: The current study demonstrated that the cardiovascular benefits of low-dose aspirin were equally balanced by major bleeding events. In addition, the potential beneficial effects might be seen in the population ≤ 70 years of age with high cardiovascular risk and no increased risk of bleeding. [ABSTRACT FROM AUTHOR]