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Aspirin Use to Prevent Cardiovascular Disease and Colorectal CancerUpdated Evidence Report and Systematic Review for the US Preventive Services Task Force

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Abstract

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.

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Article Information

Corresponding Author: Janelle M. Guirguis-Blake, MD, Kaiser Permanente Evidence-based Practice Center, Department of Family Medicine, University of Washington, 521 Martin Luther King Jr Way, Tacoma, WA 98405 (jguirgui@u.washington.edu).

Accepted for Publication: February 21, 2022.

Correction: This article was corrected on May 6, 2022, for incorrect data in the abstract, Results, and Figure 3.

Author Contributions: Dr Guirguis-Blake had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Guirguis-Blake, Evans, Perdue, Bean.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Guirguis-Blake, Evans, Perdue, Bean.

Critical revision of the manuscript for important intellectual content: Guirguis-Blake, Evans, Perdue, Senger.

Statistical analysis: Guirguis-Blake, Perdue.

Administrative, technical, or material support: Evans, Perdue, Bean, Senger.

Supervision: Guirguis-Blake, Evans.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was funded under contract HSA-290-2015-00007-I-EPC5, Task Order 9, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the US Preventive Services Task Force (USPSTF).

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or data synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.

Additional Contributions: We thank the following individuals for their contributions to this project: Howard Tracer, MD (AHRQ); current and former members of the USPSTF who contributed to topic deliberations; Steven P. Dehmer, PhD, Michael Maciosek, PhD, Lauren O’Keefe, MS, and Elizabeth Grossman, MPH, from the decision analysis team for their collaboration; Jennifer Lin, MD, for mentoring and project oversight; and Melinda Davies, MA, and Jill Pope, BA (Center for Health Research), for technical and editorial assistance. USPSTF members, peer reviewers, and those commenting on behalf of partner organizations did not receive financial compensation for their contributions.

Additional Information: A draft version of this evidence report underwent external peer review from 6 content experts (Nancy Cook, ScD, Harvard Medical School; Colin Baigent, FFPH, FRCP, Oxford University; Asad Umar, DVM, PhD, National Cancer Institute; John McNeil, PhD, Monash University; Diana Petitti, MD, MPH, Arizona State University; and Vanessa Selak, PhD, University of Auckland) and 4 federal partners (the Centers for Disease Control and Prevention; the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the National Institute on Aging). Comments were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

Editorial Disclaimer: This evidence report is presented as a document in support of the accompanying USPSTF Recommendation Statement. It did not undergo additional peer review after submission to JAMA.

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