This case study was submitted by the Duke Clinical & Translational Science Institute, a CTSA at Duke University.
Aspirin is a mainstay therapy for patients with atherosclerotic cardiovascular disease, but there are unanswered questions about the best dosage.
ADAPTABLE studied the effectiveness and safety of the two most common aspirin doses, and it served as the demonstration project for clinical trials in the Patient-Centered Outcomes Research network (PCORnet), funded by the Patient-Centered Outcomes Research Institute (PCORI).
ADAPTABLE is a pragmatic clinical trial in which 15,076 patients with established ASCVD and at high risk for ischemic events (reduced blood flow to tissues) were randomized in a 1:1 fashion to receive an aspirin dose of 81 mg/day vs 325 mg/day.
The primary endpoint is a composite of all-cause death, hospitalization for MI, or hospitalization for stroke. The primary safety endpoint is hospitalization for major bleeding with an associated blood product transfusion.
Results published in May 2021 found no differences in cardiovascular events or major bleeding between patients who took 81 mg and those who took 325 mg of aspirin daily.
In addition, this study—as the first demonstration project for pragmatic clinical trials using PCORnet—held important lessons regarding identifying a large cohort of eligible patients; engaging, recruiting, and randomly assigning patients; and performing critical follow-up.
Adrian Hernandez, MD (primary contact), Vice Dean and Executive Director, Duke Clinical Research Institute & Professor of Medicine; W. Schuyler Jones, MD, Assistant Professor of Medicine & Associate Professor in Population Health Sciences Duke University School of Medicine
Janis Curtis, MSPH
Duke Clinical & Translational Science Institute
Learn more about the project
Every year 720,000 Americans have a heart attack, and nearly 380,000 die of atherosclerotic cardiovascular disease (ASCVD), also known as hardening of the arteries. Many patients who
survive develop heart failure, stroke, and/or other cardiovascular complications.
These patients often experience chest pain, shortness of breath, and fatigue, which can lead
to significant distress and worsening quality of life. Rates of mental health illnesses such as
depression are high among both these patients and their caregivers; rates of depression may approach 66% in post-myocardial infarction (MI) patients. Coronary heart disease alone costs the US $108.9 billion each year.
Aspirin, also known as acetylsalicylic acid (ASA), is the most commonly prescribed medication for cardiovascular disease. It significantly reduces outcomes such as heart attack and stroke in patients with previous cardiovascular events and/or atherosclerosis at a cost of less than one cent per day.
However, despite a history of robust evidence generation in patients with cardiovascular disease, there are still critical unanswered questions on what dosage of aspirin is most
effective and safe. Despite dozens of clinical trials involving more than 200,000 patients, the optimal dose of aspirin has not been determined in direct comparative-effectiveness trials.
Demonstrated benefits are those that have been observed and are verifiable. Potential benefits are those logically expected with moderate to high confidence.
Methods and process of ADAPTABLE have changed how research can be done within health systems. Demonstrated.
Inform clinical practice guidelines, assisting clinicians who care for patients with ASCVD. Potential.
The study has defined the optimal dose of a low-cost drug that can enhance health promotion and disease prevention in communities or populations. Demonstrated.
This research has clinical and community implications. The framework for these implications was derived from the Translational Science Benefits Model created by the Institute of Clinical & Translational Sciences at Washington University in St. Louis.
ADAPTABLE answers the question about the most effective and safe dose of aspirin in patients with ASCVD, informing clinical practice guidelines and assisting clinicians who care for patients with ASCVD.
In addition, the methods and processes of ADAPTABLE have informed and changed how research can be done within health systems. The use of a computable phenotype led to the identification of a large potentially eligible population of patients with ASCVD in the study centers. Because aspirin is an over-the-counter medication and the trial is an open-label study, direct-to-patient approach strategies were used to initially approach a large group (~450,000) of potential participants.
Utilizing an electronic consent process and web-based patient portal, 15,076 participants were enrolled either virtually or via research coordinator/investigator assistance at a study center. The patient portal was also used for study retention and follow-up, obviating the need for participants to return to the study centers on a routine basis.
The nine Clinical Data Research Networks and their patient partners around the country were involved in every aspect of study design and conduct, including protocol review, design of patient-facing materials and the electronic consent form, and participant newsletters and blogs.
A Patient-Powered Research Network called Health eHeart centered at the University of California, San Francisco was deeply involved in all aspects of our patient engagement plans.
ADAPTABLE has defined the optimal dose of a low-cost drug (ASA) that can enhance health promotion and disease prevention in communities or populations.