Importance: Low-dose aspirin is used for primary cardiovascular disease prevention and may have benefits for colorectal cancer prevention.
Objective: To review the benefits and harms of aspirin in primary cardiovascular disease prevention and colorectal cancer prevention to inform the US Preventive Services Task Force.
Data sources: MEDLINE, PubMed, Embase, and the Cochrane Central Register of Controlled Trials through January 2021; literature surveillance through January 21, 2022.
Study selection: English-language randomized clinical trials (RCTs) of low-dose aspirin (≤100 mg/d) compared with placebo or no intervention in primary prevention populations.
Data extraction and synthesis: Single extraction, verified by a second reviewer. Quantitative synthesis using Peto fixed-effects meta-analysis.
Main outcomes and measures: Cardiovascular disease events and mortality, all-cause mortality, colorectal cancer incidence and mortality, major bleeding, and hemorrhagic stroke.
Results: Eleven RCTs (N = 134 470) and 1 pilot trial (N = 400) of low-dose aspirin for primary cardiovascular disease prevention were included. Low-dose aspirin was associated with a significant decrease in major cardiovascular disease events (odds ratio [OR], 0.90 [95% CI, 0.85-0.95]; 11 RCTs [n = 134 470]; I2 = 0%; range in absolute effects, -2.5% to 0.1%). Results for individual cardiovascular disease outcomes were significant, with similar magnitude of benefit. Aspirin was not significantly associated with reductions in cardiovascular disease mortality or all-cause mortality. There was limited trial evidence on benefits for colorectal cancer, with the findings highly variable by length of follow-up and statistically significant only when considering long-term observational follow-up beyond randomized trial periods. Low-dose aspirin was associated with significant increases in total major bleeding (OR, 1.44 [95% CI, 1.32-1.57]; 10 RCTs [n = 133 194]; I2 = 4.7%; range in absolute effects, 0.1% to 1.0%) and in site-specific bleeding, with similar magnitude.
Conclusions and relevance: Low-dose aspirin was associated with small absolute risk reductions in major cardiovascular disease events and small absolute increases in major bleeding. Colorectal cancer results were less robust and highly variable.