ACC 2021: ADAPTABLE Answers the Aspirin Question, Provides Framework for Novel Research Methods

The results provide insight into which dose may be best for most patients.

Results from a landmark clinical trial that sought to determine the safest and most effective dose of aspirin for patients with existing cardiovascular disease were presented Saturday morning as part of the 70th annual American College of Cardiology Scientific Session & Expo.

DCRI’s Schuyler Jones, MD, the principal investigator of the ADAPTABLE study, shared results in a late-breaking clinical trials session. The findings were simultaneously published in the New England Journal of Medicine.

Adaptable, the aspirin study

ADAPTABLE randomized 15,076 people with existing cardiovascular disease to receive either baby aspirin (81 mg) or regular strength aspirin (325 mg). Although aspirin is the most commonly used medication for people with cardiovascular disease to prevent a heart attack or stroke, there has been little evidence as to which dose provides the best protection while also minimizing risk of bleeding. ADAPTABLE is the largest study to date to seek the answer to this question.

Ultimately, investigators found no significant difference in either protective effects or bleeding risk between the two doses. However, the group taking the lower dose were less likely to switch doses mid-study (41.6 percent of patients taking 325 mg switched doses, as compared to 7 percent who switched from the 81 mg group). Patients in the lower dose group were also slightly less likely to discontinue aspirin completely (11 percent discontinued in the 325 mg group, as compared to 7 percent in the 81 mg group).

“Although patients may have switched doses because of tolerability, other considerations also could have factored in, such as prior patient beliefs or clinician preferences,” Jones said. “For example, nearly all of the participants were taking aspirin prior to participating in ADAPTABLE, and the majority of them were taking the lower dose. This prior experience could have led to bias about which dose was best.”

Despite the range of factors contributing to dose switching, Jones said that the ADAPTABLE results suggest that the lower dose may be better for most patients, as the two doses had similar safety and effectiveness profiles but the lower dose group saw lower rates of dose switching.

The ADAPTABLE results, which were shared with study participants in a lay-language publication and through a Town Hall recording, should prompt shared decision-making discussions—both for those who participated in the study and for the wider population of people who are taking aspirin as a secondary prevention method, Jones said. Together with clinicians, people should make the decision about which dose of aspirin is right for them.

Beyond answers for aspirin dosing, ADAPTABLE also provides many insights for the future of clinical research via its novel design. It was the first trial to leverage PCORnet®, the Patient-Centered Clinical Research Network, which is an integrated partnership of clinical research networks funded by the Patient-Centered Outcomes Research Institute (PCORI). ADAPTABLE also included many pragmatic elements, such as:

  • The ability for patients to enroll and consent to the study online
  • The opportunity for patients to report outcomes via an online portal that would typically be collected at follow-up visits—making ADAPTABLE a virtual study
  • The collection of patient information from electronic health records linked with Medicare and private insurance information
  • Engagement with patient partners at all levels of the study, from protocol design to creation of study materials to dissemination of results

“We learned so many incredible things from ADAPTABLE about how to streamline processes and alleviate the burden of participating in research for both sites and patients,” Jones said. “From its remote follow-up techniques to its engagement with patient partners, ADAPTABLE provides a blueprint for how research can be improved in the future.”

Moving forward, the ADAPTABLE team will be running additional exploratory analyses to better understand the factors that contributed to dose switching during the study.

In addition to Jones, DCRI contributors to ADAPTABLE include Adrian Hernandez, MD, MHS; Amber Sharlow, MBA, CCRA; Lesley Curtis, PhD; Brad Hammill, DrPH; Debra Harris; Laura Qualls, MS; Hillary Mulder, MS; Lisa Wruck, PhD, MSPH; Michael Pencina, PhD; and Patty McAdams. Former DCRI contributors include Matthew Roe, MD; Lisa Berdan, PA, MHS; Guillaume Marquis-Gravel, MD, MSc; and Holly Robertson, PhD, PMP.