A novel, large-scale aspirin trial concluded by offering dose guidance for patients with cardiovascular disease. But the most significant legacy of the three-year study may be its influence on future large-scale clinical studies.
Published in the New England Journal of Medicine (NEJM) in May, the Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness trial (ADAPTABLE) trial answers a question asked by clinicians and patients for years, says W. Schuyler Jones, MD, a Duke cardiologist, principal investigator of the study, and lead author of the NEJM analysis.
The trial determined that a lower dose of aspirin (81 mg) is as effective as the higher dose (325 mg) with no differences in the rates of major bleeding. Clinicians are advised to recommend patients use the lower dose.
“The consensus of the study is that patients who were assigned to the two aspirin doses had similar effectiveness and safety event rates, and that low dose aspirin provides enough antiplatelet and anti-inflammatory action that it balances the risk of an ischemic event as well as the risk of bleeding from the higher dose,” Jones says.
ADAPTABLE used an open-label, pragmatic design to randomly assign patients with established atherosclerotic cardiovascular disease to 81 or 325 mg of aspirin daily. The trial involved more than 15,000 patients followed for a median time of 26.2 months. The trial methodology, described as pragmatic, attracted a great deal of attention among researchers, Jones says, because of the low barriers to participate and a new model of patient engagement in the project. The analysis featured several distinctions from traditional randomized clinical trials:
- A new recruitment method
- Electronic informed consent
- Patient-directed enrollment and randomization
- Remote data collection
Open-label study model presented challenges
“There are two big angles to the ADAPTABLE story,” says Jones. “First, of course, is the aspirin dose recommendation. But the other important element relates to how this study was done and what that means for future studies.”
The study was conducted in an open-label fashion, and the model did present challenges. “The big concern was that we discovered a lot of dose switching within the group taking the 325 mg aspirin dose,” Jones says. “We noted many reasons for this dose switching, including patient and clinician preferences, and these issues may have introduced bias and complicated the interpretation of results.”
But as a result of ADAPTABLE, new trials are underway. Investigators are adapting the pragmatic emphasis points in future studies, Jones says. An analysis of the use of a statin or a placebo in helping prevent dementia among patients over 75 has been launched using the aspirin trial model.
“The lessons learned from ADAPTABLE are important and they include gathering already-collected clinical practice data from a huge trial population, partnering with patient advocates, and avoiding open-label problems in the future versions of pragmatic clinical trials,” Jones says.