Every year, 720,000 Americans have a heart attack, and nearly 380,000 die of coronary artery disease (CAD). Many of the patients who survive develop heart failure, stroke, or other cardiovascular complications. These conditions lead to substantial symptomatic, emotional, and functional difficulties for patients with CAD. Although novel therapies for treating CAD are needed, increasing the use of an inexpensive yet effective therapy, such as aspirin, will likely have a much greater effect on death and disability globally. To date, however, the best dose of aspirin (i.e., the one resulting in the lowest risk of ischemic and bleeding events) for the general population with ischemic heart disease has not been determined. Given the substantial burden of CAD and the continued growth of the population affected by it, defining the optimal aspirin dose will save thousands of lives globally.
The main objective of this pragmatic randomized clinical trial (PCT) is to identify the optimal dose of aspirin for secondary prevention in atherosclerotic cardiovascular disease (ASCVD). This trial will constitute the initial randomized comparative-effectiveness trial conducted by PCORnet: The National Patient-Centered Clinical Research Network.
This PCT will incorporate several essential aspects of the new genre of patient-centered comparative effectiveness trials:
- By using existing data sources to gather baseline characteristics and a combination of existing data and patient-reported outcomes during follow-up, the PCT will answer its critical question at a relatively low cost;
- an Internet portal will enable the PCT to collect and monitor data and allow for learning by both patients and clinicians, capitalizing on the frequent use of the Internet by the American public and clinicians;
- the PCT will not have a placebo control but instead will provide all patients with active treatment at different doses, with careful monitoring to balance benefit and risk;
- patient-reported outcomes will be collected;
- the evolving PCORnet infrastructure will be used to streamline administrative aspects of the trial, including centralization of IRB functions and contracts, electronic consent, and use of EHR and claims data;
- mechanistic studies that include genetic testing and platelet physiology studies may be performed to improve our understanding of the variable responses of patients to specific doses of aspirin if additional funding is garnered for a sub-study in a limited number of participants.
This PCT will allow us to identify the optimal dose of aspirin—one that will provide maximal benefit to patients with ASCVD, with low risk of bleeding. This PCT will save lives and reduce the burden of morbidity resulting from ASCVD globally.
Visit the ADAPTABLE: The Aspirin Study website.
Grady C, Cummings SR, Rowbotham MC, et al., Informed Consent. The New England Journal of Medicine (March 2017).
Johnston A, Jones WS, Hernandez AF. The ADAPTABLE Trial and Aspirin Dosing in Secondary Prevention for Patients with Coronary Artery Disease. Current Cardiology Reports (August 2016).
Hernandez AF, Fleurence RL, Rothman RL. The ADAPTABLE Trial and PCORnet: Shining Light on a New Research Paradigm. Annals of Internal Medicine (August 2015).
Which Aspirin Dose Is Best to Protect Patients with Heart Disease? Our First PCORnet Study
In this blog post, PCORI Executive Director Joe Selby, MD, MPH, wrote about the Board of Governors' approval of funding for this study, and discussed some of the key aspects of its design and goals.
VIDEO: PCORnet's First Pragmatic Clinical Trial
Dr. Russell Rothman explains the significance of the ADAPTABLE study and novel aspects of its design as a pragmatic clinical trial.