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Evaluation of the Benefits and Harms of Aspirin for Primary Prevention of Cardiovascular Events

A Comparison of Quantitative Approaches

Methods Research Reports

Investigators: , MD, PhD, , MD, MPH, , MD, MHS, , PhD, , BSc, and , MD, MPH.

Author Information and Affiliations
Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 12(14)-EHC149-EF

Structured Abstract


Prior work has described various quantitative approaches to the assessment of benefits and harms of medical interventions. Researchers rarely use these approaches in the context of a systematic review.


Our objectives were to illustrate two quantitative approaches to assessing benefits and harms in the context of a systematic review, and to determine the methodological challenges of applying these approaches in a systematic review.


We compared the number-needed-to-treat (NNT) and number-needed-to-harm (NNH) approach and the Gail/National Cancer Institute (NCI) approach for assessing the benefits (prevention of myocardial infarction [MI] and ischemic stroke) and harms (excess of hemorrhagic stroke and major gastrointestinal [GI] bleeds) of aspirin for primary prevention of cardiovascular events. We based our main analyses for these two approaches on the treatment effects from a meta-analysis of large primary prevention trials, and the incidence rates from observational studies. We focused on observational studies that were most applicable to our target population—aged 50 to 84 years, living in the United States without evidence of cardiovascular disease or stroke. We obtained relative weights denoting the relative importance of different outcomes (required by the Gail/NCI approach) from literature sources. These sources weighted major stroke nearly twice as much as MI and nearly eight times as much as major GI bleeds.


The NNT and NNH for aspirin declined with increasing age because of the increase in baseline incidence rates for all outcomes across age categories as obtained from observational studies. For example, in men aged 45–54, the NNT was 1,786 person-years of treatment to prevent one MI, and the NNH was 1,344 person-years of treatment to induce one major GI bleed (which corresponds to 5.6 MI prevented and 57.4 GI bleeds induced if 1,000 people are treated with aspirin for 10 years, compared with no aspirin use). For men aged 75–84, the NNT was 511 to prevent one MI and the NNH was 202 to induce one major GI bleed. A sensitivity analysis that considered different baseline incidence rates from randomized trials showed a much higher NNH for GI bleeds because the baseline incidence rate of that outcome was 2–3 times lower than in observational studies.

When we used relative weights, the Gail/NCI approach showed that aspirin caused more benefit than harm in all age categories of men and women. When we weighted outcomes equally in a sensitivity analysis, the harm from aspirin was greater compared with the main analysis because of greater relative weight for GI bleeds. When we weighted stroke as a very important outcome (weight of 1), MI as an important outcome (weight of 0.5), and GI bleed as an unimportant outcome (weight of 0), aspirin was associated with net benefit for all sex and age categories.

When comparing the two approaches in terms of estimates for a single outcome, we found comparable results for the number of people who would have a benefit or harm from treatment as long as the baseline incidence rates and the competing risk (all-cause mortality) were small. When the impact of the competing risk was larger, we found substantial differences between the NNT and NNH and Gail/NCI approaches, even though the baseline incidence rates and treatment effects used were identical.


The assessment of benefits and harms requires careful selection and integration of data from disparate sources, including baseline risks of events without treatment, the effects of treatments on various outcomes, and relative weights of these outcomes. We have illustrated that quantitative approaches are feasible in a specific decisionmaking context—using data from a systematic review of aspirin for primary prevention. Quantitative approaches can yield different results even if input data for baseline risks and treatment effects are identical. Quantitative approaches can be particularly valuable in demonstrating how the expected balance of benefits and harms depends on assumptions about the relative weights of different outcomes.

Updated February 2014

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. 290-2007-10061-I, Prepared by: Johns Hopkins University Evidence-based Practice Center, Baltimore, MD

Suggested citation:

Puhan MA, Singh S, Weiss CO, Varadhan R, Sharma R, Boyd CM. Evaluation of the Benefits and Harms of Aspirin for Primary Prevention of Cardiovascular Events: A Comparison of Quantitative Approaches. Methods Research Report. (Prepared by Johns Hopkins University Evidence-based Practice Center under contract No. 290-2007-10061-I). AHRQ Publication No. 12(14)-EHC149-EF. Rockville, MD: Agency for Healthcare Research and Quality. November 2013. Updated February 2014. www.effectivehealthcare.ahrq.gov/reports/final.cfm

This report is based on research conducted by the Johns Hopkins University Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. Contract No. 290-2007-10061-I). The findings and conclusions in this document are those of the author(s), who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

This report may periodically be assessed for the urgency to update. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program Web site at www.effectivehealthcare.ahrq.gov. Search on the title of the report.

None of the investigators have any affiliations or financial involvement that conflict with the material presented in this report.


540 Gaither Road, Rockville, MD 20850; www​.ahrq.gov

Bookshelf ID: NBK179079PMID: 24404631


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