Steven P. Dehmer, PhD; Michael V. Maciosek, PhD; Thomas J. Flottemesch, PhD; Amy B. LaFrance, MPH; Evelyn P. Whitlock, MD, MPH
Disclaimer: The views expressed in this article do not represent and should not be construed to represent a determination or policy of the Agency for Healthcare Research and Quality (AHRQ) or the U.S. Department of Health and Human Services.
Acknowledgment: The authors gratefully acknowledge the following persons for their contributions to this project: Robert McNellis, PA, MPH, at the AHRQ; Kirsten Bibbins-Domingo, PhD, MD, MAS, Michael L. LeFevre, MD, MSPH, Douglas K. Owens, MD, MS, and Michael P. Pignone, MD, MPH, of the USPSTF; Janelle M. Guirguis-Blake, MD, Jessica Chubak, PhD, MBHL, Melissa L. Anderson, MS, Tracy Beil, MS, Diana S.M. Buist, PhD, MPH, Brittany U. Burda, MPH, Corinne V. Evans, MPP, Alisha Feightner, MPH, Aruna Kamineni, PhD, MPH, Elizabeth A. O'Connor, PhD, Maya G. Rowland, MPH, Caitlyn A. Senger, MPH, and Selvi B. Williams, MD, MPH, with the Kaiser Permanente Research Affiliates Evidence-based Practice Center; and Logan H. Stuck, MS, at the HealthPartners Institute. The following persons provided peer review of the work plan, full evidence report, or both: Dong-Yun Kim, PhD, William Lawrence, MD, MS, Michael Pignone, MD, MPH, Glen Taksler, PhD, and Steven Teutsch, MD, MPH.
Financial Support: By contract HHSA-290-2012-00015-EPC4, Task Order 4, 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=M15-2129.
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 from Dr. Dehmer (e-mail, firstname.lastname@example.org). Statistical code and data set: Please contact Dr. Dehmer (e-mail, email@example.com) for availability (some restrictions may apply).
Requests for Single Reprints: Reprints are available from the AHRQ Web site (www.ahrq.gov).
Current Author Addresses: Drs. Dehmer and Maciosek and Ms. LaFrance: HealthPartners Institute, Mailstop 21111R, PO Box 1524, Minneapolis, MN 55440.
Dr. Flottemesch: Truven Health Analytics, 777 East Eisenhower Parkway, Ann Arbor, MI 48108.
Dr. Whitlock: Patient-Centered Outcomes Research Institute, 1828 L Street, Northwest, Suite 900, Washington, DC 20036.
Author Contributions: Conception and design: S.P. Dehmer, M.V. Maciosek, T.J. Flottemesch, E.P. Whitlock.
Analysis and interpretation of data: S.P. Dehmer, M.V. Maciosek, T.J. Flottemesch, A.B. LaFrance, E.P. Whitlock.
Drafting of the article: S.P. Dehmer, M.V. Maciosek.
Critical revision of the article for important intellectual content: S.P. Dehmer, M.V. Maciosek, T.J. Flottemesch, LaFrance, E.P. Whitlock.
Final approval of the article: S.P. Dehmer, M.V. Maciosek, T.J. Flottemesch, A.B. LaFrance, E.P. Whitlock.
Statistical expertise: T.J. Flottemesch, S.P. Dehmer.
Obtaining of funding: M.V. Maciosek, E.P. Whitlock.
Administrative, technical, or logistic support: A.B. LaFrance.
Collection and assembly of data: S.P. Dehmer, T.J. Flottemesch, E.P. Whitlock.
Evidence indicates that aspirin is effective for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) but also increases the risk for gastrointestinal (GI) and cerebral hemorrhages.
To assess the net balance of benefits and harms from routine aspirin use across clinically relevant age, sex, and CVD risk groups.
Decision analysis using a microsimulation model.
3 systematic evidence reviews.
Men and women aged 40 to 79 years with a 10-year CVD risk of 20% or less, and no history of CVD and without elevated risk for GI or cerebral hemorrhages that would contraindicate aspirin use.
Lifetime, 20 years, and 10 years.
Low-dose aspirin (≤100 mg/d).
Primary outcomes are length and quality of life measured in net life-years and quality-adjusted life-years. Benefits include reduced nonfatal myocardial infarction, nonfatal ischemic stroke, fatal CVD, CRC incidence, and CRC mortality. Harms include increased fatal and nonfatal GI bleeding and hemorrhagic stroke.
Lifetime net quality-adjusted life-years are positive for most adults initiating aspirin at ages 40 to 69 years, and life expectancy gains are expected for most men and women initiating aspirin at ages 40 to 59 years and 60 to 69 years with higher CVD risk. Harms may exceed benefits for persons starting aspirin in their 70s and for many during the first 10 to 20 years of use.
Results are most sensitive to the relative risk for hemorrhagic stroke and CVD mortality but are affected by all relative risk estimates, baseline GI bleeding incidence and case-fatality rates, and disutilities associated with aspirin use.
Aspirin effects by age are uncertain. Stroke benefits are conservatively estimated. Gastrointestinal bleeding incidence and case-fatality rates account only for age and sex.
Lifetime aspirin use for primary prevention initiated at younger ages (40 to 69 years) and in persons with higher CVD risk shows the greatest potential for positive net benefit.
Agency for Healthcare Research and Quality.
Benefits and harms of routine aspirin use vary among individuals.
This modeling study suggested that lifetime aspirin use for primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) had potential net benefits for most men and women who did not have elevated bleeding risk and initiated aspirin use at ages 40 to 69 years. Overall benefits did not outweigh harms for persons in their 70s with a 10-year CVD risk of 20% or less.
Estimates of aspirin effects by age were uncertain.
Middle-aged men and women without elevated risk for gastrointestinal or cerebral hemorrhage should consider long-term aspirin use to prevent CVD and CRC.
Table 1. Key Aspirin Benefit and Harm Parameter Values*
Appendix Table 1. Health Utility Weights*
Simulation model and analysis design.
BMI = body mass index; BP = blood pressure; CRC = colorectal cancer; CVD = cardiovascular disease; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; SBP = systolic blood pressure.
Appendix Table 2. Comparison of Baseline Modeled CVD Event Rates With National Prevalence Estimates*
Appendix Table 3. Baseline GI Bleeding and Case-Fatality Rate Parameter Values*
Table 2. Net Life-Years and QALYs of Lifetime, 20-y, and 10-y Aspirin Use*
Table 3. Detailed Benefit and Harm Tradeoffs of Aspirin Use With a CVD Risk of 10%*
Appendix Table 4. Expanded Lifetime Benefit and Harm Tradeoffs of Aspirin Use for Men Aged 40–79 y*
Appendix Table 5. Expanded Lifetime Benefit and Harm Tradeoffs of Aspirin Use for Women Aged 40–79 y*
Appendix Table 6. Comparisons in Lifetime Net Benefit of Taking Aspirin for Men and Women With a CVD Risk of 10%*
Appendix Table 7. Comparisons in Net Benefit of Taking Aspirin Over 20 y for Men and Women With a CVD Risk of 10%*
Appendix Table 8. Comparisons in Net Benefit of Taking Aspirin Over 10 y for Men and Women With a CVD Risk 10%*
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Gen-Min Lin, Chih-Lu Han, Ching-Fen Wu, Wen-Been Wang, Shih-Ping Yang, Yi-Hwei Li
Hualien-Armed Forces General Hospital, Taipei Veteran General Hospital, Mannonite Christian Hospital, Tri-Service General Hospital, Tzu-Chi University
June 26, 2016
Aspirin for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer in Patients with Diabetes Mellitus
Dear Editor:We appreciate the work by professor Dehmer and colleagues, which reported that lifetime low-dose aspirin use for primary prevention of future cardiovascular disease (CVD) and colorectal cancer initiated at younger ages (40 to 69 years) and in persons with higher CVD risk shows the greatest potential for positive net benefit if the adverse bleeding effect of aspirin was considered (1). Notably in 2013, the American Diabetes Association (ADA), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) have suggested diabetic adults free of vascular disease at baseline who are at increased risk of CVD (2). This includes men >50 years old and most women >60 years old. Aspirin is not recommended for diabetic patients who have a low risk of CVD, such as men <50 years old and women <60 years old with no major vascular risk factors. Additionally, aspirin might be recommended in those with an intermediate risk of CVD. This joint statement by ADA/AHA/ACCF is somewhat conflicting to the conclusion of present study, particularly for the threshold of age initiated the use of aspirin in men and women with diabetes.As we know, diabetes is an independent risk factor of not only CVD but also colorectal cancer, especially in obese individuals (3). Since the joint statement by ADA/AHA/ACCF mainly focused on the CVD risk in adults, the benefit of aspirin use for the prevention of colorectal cancer might be overlooked. However, the evaluation of CVD risk factors did not include diabetes status in the present study that we could not comply the results with the previous joint recommendations by ADA/AHA/ACCF. In our opinion, it is worth for the authors to do further analyses specifically for patients with diabetes. Whether low dose aspirin prophylaxis could provide the greatest potential for positive net benefit as early as their 40 years old needs clarifications. References1. Dehmer SP, Maciosek MV, Flottemesch TJ, LaFrance AB, Whitlock EP. Aspirin for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: A Decision Analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2016; 164:777-86.2. Aspirin Therapy in Patients with Diabetes: An Update on Current Recommendations3. Peeters PJ, Bazelier MT, Leufkens HG, de Vries F, De Bruin ML. The risk of colorectal cancer in patients with type 2 diabetes: associations with treatment stage and obesity. Diabetes Care. 2015; 38:495-502.
Dehmer SP, Maciosek MV, Flottemesch TJ, LaFrance AB, Whitlock EP. Aspirin for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: A Decision Analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164:777-786. doi: 10.7326/M15-2129
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Published: Ann Intern Med. 2016;164(12):777-786.
Published at www.annals.org on 12 April 2016
Cardiology, Coronary Risk Factors, Prevention/Screening.
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