Final Research Plan: Aspirin to Prevent Cardiovascular Disease
Final Research Plan for 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.
The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Report will form the basis of the USPSTF Recommendation Statement on this topic.
The draft Research Plan was available for comment from July 11 until August 7, 2013 at 5:00 p.m., ET.
Abbreviations: CVD = cardiovascular disease; MI = myocardial infarction.
The figure is an 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 may result in a decrease in myocardial infarction, ischemic stroke, and mortality related to all causes and cardiovascular disease (KQ 1). The figure also depicts whether regular aspirin use is associated with any potential harms (KQ 2).
Key Questions to Be Systematically Reviewed
- Does regular aspirin use in persons without known cardiovascular disease reduce myocardial infarction (MI), stroke, death from MI or stroke, or all-cause mortality?
- Does the effect of aspirin vary between a priori subgroups, such as age, sex, smoking status, race/ethnicity, 10-year cardiovascular risk, or related risk conditions (e.g., diabetes mellitus, decreased ankle–brachial index, or elevated blood pressure)?
- Does the effect of aspirin vary by dose, formulation (enteric coated), or duration of use?
- Does regular aspirin use increase gastrointestinal bleeding, hemorrhagic stroke, or other serious harms (e.g., age-related macular degeneration)?
- Does the effect of aspirin vary by subgroup characteristics, such as age, sex, smoking status, race/ethnicity, 10-year cardiovascular risk, related risk conditions (e.g., diabetes mellitus, decreased ankle–brachial index, or elevated blood pressure), gastrointestinal bleeding or hemorrhagic stroke risk factors (including history of gastrointestinal bleeding, ulcers, or nonsteroidal anti-inflammatory drug use), or concomitant medication use (nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, or proton pump inhibitors)?
- Does the effect of aspirin vary by dose, formulation, or duration of use?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- Which of the accepted and available cardiovascular risk prediction tools commonly used in practice are good candidates to guide therapeutic decisionmaking for aspirin use?
- Do these cardiovascular risk prediction tools vary by subgroup?
- What are the characteristics of patient preferences with respect to the trade-off of the benefits and harms of aspirin chemoprevention (i.e., do patients value averted cardiovascular events more or less highly than incurred harms)?
The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Report. Criteria are overarching as well as specific to each of the key questions (KQs).
|Aim||Primary prevention of cardiovascular disease: MI, stroke, death from MI or stroke, or all-cause mortality||Secondary and tertiary prevention of MI, stroke, death from MI or stroke, or all-cause mortality|
|Populations||Adults age 40 years and older without known cardiovascular disease||Nonhuman populations; other selected nongeneralizable populations; patients with an existing cardiovascular disease diagnosis or history (heart failure, previous stroke, previous MI, transient ischemic attack, angina, or previous bypass or angioplasty); patients with atrial fibrillation; patients with familial hypercholesterolemia; patients with hypercoagulable disorders; children and young adults (age <40 years)|
|Interventions||Regular oral aspirin use (minimum of 75 mg every other day); exposure of at least 12 months||Nonaspirin antithrombotic medications; studies that do not provide information on dose; interventions limited to irregular or occasional use only; studies in which aspirin is a cotreatment; nonoral, nontablet forms of aspirin; exposure of less than 12 months|
|Comparisons||Placebo or no treatment||Any active substance or intervention (e.g., nonaspirin medication, dietary supplements, dietary change, weight loss)|
|Outcomes||KQ 1: MI, stroke, death from MI or stroke, all-cause mortality, or quality of life
KQ 2: Gastrointestinal bleeding, hemorrhagic stroke, or other serious harms (e.g., age-related macular degeneration)
|KQ 1: Intermediate markers of cardiovascular disease (e.g., calcium scores, intima media thickness, asymptomatic electrocardiography findings); intermediate markers of platelet function or clotting (e.g., in vitro clotting time, platelet aggregation)
KQ 2: Intermediate markers of platelet function or clotting
|Study Design||KQ 1: Randomized, controlled trials; controlled clinical trials; systematic reviews and meta-analyses of randomized, controlled trials
KQ 2: Randomized, controlled trials; controlled clinical trials; large prospective cohort studies
|KQ 1: Observational studies (cohort, case control, case studies, or case series)
KQ 2: Case-control, case studies, or case series
|Timing of outcome assessment||12 months or longer||Less than 12 months|
|Country||Any country with a 2013 Human Development Index of “Very High”||Any country with less than a Human Development Index of “Very High”|
|Language||English||Languages other than English|
|Study Quality||Good and fair quality, according to USPSTF criteria||Poor quality, as defined by design-specific USPSTF criteria|
Response to Public Comment
The draft Research Plan was posted for public comment on the U.S. Preventive Services Task Force (USPSTF) Web site from July 11 to August 7, 2013. The USPSTF reviewed and considered all comments received and made minor changes to the Research Plan in response. The age range for the population of interest was changed from persons age 18 years and older to persons age 40 years and older to better reflect the potential target population for the intervention. In addition, the term “regular” aspirin use was substituted for “low dose” aspirin use to avoid confusion. The variety of dosages used in the trials will be characterized in the evidence report.
Internet Citation: Final Research Plan: Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication. U.S. Preventive Services Task Force. October 2013.