Final Research Plan

Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

May 14, 2020

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Figure 1 is the analytic framework that depicts the two Key Questions to be addressed in the systematic review. The figure illustrates how regular aspirin use in patients without known cardiovascular disease (CVD) may reduce CVD- and colorectal cancer (CRC) incidence and mortality, or all-cause mortality  (KQ1). Additionally, the figure depicts the posibility that regular aspirin use increases the incidence of major gastrointestinal bleeding, intracranial bleeding, or other serious harms (KQ2).

Abbreviations: CRC = colorectal cancer; CVD = cardiovascular disease.

  1. Does regular aspirin use in patients without known cardiovascular disease (CVD) reduce CVD and colorectal cancer (CRC) incidence and mortality, or all-cause mortality?
    1. Does the effect vary between a priori subgroups defined by age, sex, 10-year cardiovascular risk, diagnosis of diabetes mellitus, or race/ethnicity?
    2. Does the effect vary by dose or duration of aspirin use?
  2. Does regular aspirin use increase major gastrointestinal bleeding, intracranial bleeding, or other serious harms?
    1. Does the effect vary between a priori subgroups defined by age, sex, 10-year cardiovascular risk, diagnosis of diabetes mellitus, race/ethnicity, or bleeding risk factors?
    2. Does the effect vary by dose or duration of aspirin use?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. Current recommendations for aspirin use involve CVD risk estimation using the Pooled Cohort Equations. Are there patient populations for whom CVD risk is underestimated or overestimated using the Pooled Cohort Equations?
  2. What is the effect of aspirin discontinuation on CVD, CRC, all-cause mortality, and bleeding outcomes?
  3. What are the performance, applicability, and implementation characteristics of the most promising currently available bleeding risk prediction models?
Category Included Excluded
Aim Primary prevention of CVD, CRC, and/or all-cause mortality Secondary and tertiary prevention of CVD or CRC
Populations Adults age ≥40 years without known CVD and at average risk for CRC or unselected for CRC risk* Other selected nongeneralizable populations (e.g., those with genetic susceptibility syndromes or personal history of cancer)
Interventions Regular oral aspirin use (at least 75 mg every other day) for 12 months Coadministration with other nonaspirin antithrombotic medications (e.g., warfarin)
Comparisons Placebo or no treatment Any active substance or intervention
Outcomes KQ 1: Myocardial infarction, stroke, death from myocardial infarction or stroke, CRC incidence, CRC mortality, and all-cause mortality

KQ 2: Major bleeding, defined as bleeding requiring transfusion or hospitalization or leading to death (including but not limited to gastrointestinal bleeding), hemorrhagic stroke, or other serious harms

KQ 1: Intermediate markers of CVD (e.g., calcium scores, intimal medial thickness, or asymptomatic electrocardiography findings); intermediate markers of platelet function or clotting

KQ 2: Postoperative or minor bleeding

Study Designs All KQs: Good- and fair-quality studies, according to USPSTF criteria

KQ 1: Randomized, controlled trials; controlled clinical trials; and individual patient data meta-analyses

KQ 2: Randomized, controlled trials; controlled clinical trials; individual patient data meta-analyses; and large prospective observational studies

All KQs: Poor-quality studies, according to USPSTF criteria

KQ 1: Observational studies

KQ 2: Retrospective cohort studies, case control studies, case series, case reports, narrative reviews, commentaries, or editorials

Setting Studies conducted in countries categorized as “very high” on the 2017 Human Development Index, as defined by the United Nations Development Programme  

*For CRC outcomes only, populations with and without a history of CVD will be included.

The USPSTF has commissioned a decision model to supplement the systematic evidence review on the use of aspirin to prevent CVD and CRC, as it did for the previous topic update in 2016. The decision model is a mathematical simulation that projects the health outcomes that result from aspirin use for the prevention of CVD and CRC. In conjunction with the evidence review, the decision model will help the USPSTF examine the benefits and harms of aspirin use to prevent CVD and CRC at the population level and over different time horizons, and whether the net balance of benefits and harms varies by age, sex, CVD risk, or other subgroup characteristics.

The draft Research Plan was posted from January 30, 2020 to February 26, 2020. In response to public comment, race/ethnicity was added as an a priori subgroup for both key questions. The availability of other subgroups, such as those defined by CRC risk, will be audited and addressed in the report according to USPSTF subgroup methods.