Janelle M. Guirguis-Blake, MD; Corinne V. Evans, MPP; Caitlyn A. Senger, MPH; Elizabeth A. O'Connor, PhD; Evelyn P. Whitlock, MD, MPH
Note: This review was conducted by the Kaiser Permanente Research Affiliates Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ). The staff of AHRQ provided oversight for the project and assisted in the external review of the companion draft evidence synthesis.
Disclaimer: The views expressed in this manuscript do not represent and should not be construed to represent a determination or policy of the AHRQ or the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank the following persons for their contributions to this project: AHRQ staff; the U.S. Preventive Services Task Force; Steven Teutsch, MD, Diana Petitti, MD, MPH, Nancy R. Cook, ScD, Mark Alberts, MD, FAHA, and colleagues at the Centers for Disease Control and Prevention's National Center for Chronic Disease Prevention and Health Prevention who provided expert review of the report; and Maya Rowland, MPH, Brittany Burda, MPH, Keshia Bigler, BS, Kevin Lutz, MFA, and Smyth Lai, MLS, at the Kaiser Permanente Center for Health Research.
Financial Support: By contract HHSA-290-2012-00015-EPC4, Task Order 2, from AHRQ.
Disclosures: The authors report a contract with AHRQ during the conduct of the study. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-2113.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available at www.uspreventiveservicestaskforce.org/Page/Document/final-research-plan-aspirin-to-prevent-cardiovascular-diseas/aspirin-to-prevent-cardiovascular-disease-and-cancer. Statistical code: Not available. Data set: Available at www.ncbi.nlm.nih.gov/books/NBK321623.
Requests for Single Reprints: Reprints are available from the AHRQ Web site (www.ahrq.gov).
Current Author Addresses: Dr. Guirguis-Blake: University of Washington, Department of Family Medicine, Tacoma Family Medicine Residency Program, 521 Martin Luther King Jr. Way, Tacoma, WA 98405.
Dr. O'Connor, Ms. Evans, and Ms. Senger: Kaiser Permanente Center for Health Research, 3800 North Interstate Avenue, Portland, OR 97227.
Dr. Whitlock: Patient-Centered Outcomes Research Institute, 1828 L. Street, Northwest, Suite 900 Washington, DC 20036.
Author Contributions:Conception and design: J. Guirguis-Blake, C.V. Evans, C.A. Senger, E.P. Whitlock.
Analysis and interpretation of data: J. Guirguis-Blake, C.V. Evans, C.A. Senger, E.A. O'Connor, E.P. Whitlock.
Drafting of the article: J. Guirguis-Blake, C.V. Evans, C.A. Senger.
Critical revision of the article for important intellectual content: J. Guirguis-Blake, C.V. Evans, C.A. Senger, E.P. Whitlock.
Final approval of the article: J. Guirguis-Blake, C.V. Evans, C.A. Senger, E.A. O'Connor, E.P. Whitlock.
Statistical expertise: E.A. O'Connor.
Administrative, technical, or logistic support: C.V. Evans, C.A. Senger.
Collection and assembly of data: J. Guirguis-Blake, C.V. Evans, C.A. Senger, E.P. Whitlock.
Guirguis-Blake JM, Evans CV, Senger CA, O'Connor EA, Whitlock EP. Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164:804-813. doi: 10.7326/M15-2113
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Published: Ann Intern Med. 2016;164(12):804-813.
Published at www.annals.org on 12 April 2016
Cardiovascular disease (CVD) is the leading cause of death in the United States.
To update a systematic review about the benefits of aspirin for the primary prevention of cardiovascular events in adults aged 40 years or older and to evaluate effect modification in subpopulations.
MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (January 2008 to January 2015), and Cochrane Database of Systematic Reviews.
Two investigators independently reviewed 3396 abstracts and 65 articles according to prespecified criteria. All included trials evaluated aspirin for the primary prevention of cardiovascular events.
Two investigators assessed study quality; data were abstracted by 1 reviewer and checked by a second.
Two good-quality and 9 fair-quality randomized, controlled trials were identified. In analyses of all doses, aspirin reduced the risk for nonfatal myocardial infarction (MI) (relative risk [RR], 0.78 [95% CI, 0.71 to 0.87]) but not nonfatal stroke; aspirin showed little or no benefit for all-cause or cardiovascular mortality. Benefits began within the first 5 years. Older adults achieved greater relative MI reduction, but no other effect modifications were found in analyzed subpopulations. In trials with aspirin doses of 100 mg or less per day, the reduction in nonfatal MI benefit persisted (absolute risk reduction, 0.15 to 1.43 events per 1000 person-years) and a 14% reduction in nonfatal stroke benefit was noted, but no benefit was found for all-cause mortality (RR, 0.95 [CI, 0.89 to 1.01]) or cardiovascular mortality (RR, 0.97 [CI, 0.85 to 1.10]).
Evidence for aspirin in primary prevention is heterogeneous and limited by rare events and few credible subgroup analyses.
The beneficial effect of aspirin for the primary prevention of CVD is modest and occurs at doses of 100 mg or less per day. Older adults seem to achieve a greater relative MI benefit.
Agency for Healthcare Research and Quality.
Analytic framework with key questions.
CVD = cardiovascular disease; MI = myocardial infarction; NSAID = nonsteroidal anti-inflammatory drug; PPI =protein-pump inhibitor; SSRI = selective serotonin reuptake inhibitor.
Summary of evidence search and selection.
KQ = key question.
Appendix Table. Methodological and Intervention Characteristics of Included Trials for Primary Prevention of Cardiovascular Events
Benefits of aspirin for nonfatal MI and nonfatal stroke.
AAA = Aspirin for Asymptomatic Atherosclerosis; ABI = ankle—brachial index; BMD = British Male Doctors Trial; CG = control group; CVD = cardiovascular disease; ETDRS = Early Treatment Diabetic Retinopathy; HOT = Hypertension Optimal Treatment; IG = intervention group; JPAD = Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes; JPPP = Japanese Primary Prevention Project; MI = myocardial infarction; PHS = Physicians' Health Study; POPADAD = Prevention of Progression of Arterial Disease and Diabetes; PPP = Primary Prevention Project; RR = relative risk; TPT = Thrombosis Prevention Trial; WHS = Women's Health Study.
Benefits of aspirin for CVD mortality and all-cause mortality.
AAA = Aspirin for Asymptomatic Atherosclerosis; ABI = ankle–brachial index; BMD = British Male Doctors Trial; CG = control group; CVD = cardiovascular disease; ETDRS = Early Treatment Diabetic Retinopathy; HOT = Hypertension Optimal Treatment; IG = intervention group; JPAD = Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes; JPPP = Japanese Primary Prevention Project; PHS = Physicians' Health Study; POPADAD = Prevention of Progression of Arterial Disease and Diabetes; PPP = Primary Prevention Project; RR = relative risk; TPT = Thrombosis Prevention Trial; WHS = Women's Health Study.
Table 1. Pooled Estimates for All Included Trials and Trials With Aspirin Doses of ≤100 mg/d
Table 2. Absolute Risk Reduction With Low-Dose Aspirin Use ≤10 Years
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