ADAPTABLE Study Finds Optimal Aspirin Dose Could Come Down to Patient Preference

The ADAPTABLE study from DCRI suggests patients with existing CVD saw similar outcomes whether they were receiving 81 mg or 325 mg aspirin, but also suggests patients with the higher dose were more likely to discontinue therapy.

A new study has returned an answer to the age-old question: what is the optimal aspirin dose for prevention of cardiovascular events?

Results of the ADAPTABLE study indicate there were no major differences in events or major bleeding in patients with existing cardiovascular disease, regardless of whether they were taking the 81 and 325 mg daily doses of aspirin, but investigators noted discontinuation was markedly lower with the 81 mg dose.

“Earlier studies have primarily investigated aspirin—either 81 or 325 mg daily dose—compared with placebo, whereas ADAPTABLE was a direct comparison of the two doses,” said lead investigator Schuyler Jones, MD, assistant professor of medicine at the Duke Clinical Research Institute (DCRI), which is part of the Duke University School of Medicine, in a statement. “We found that there is no difference between the two doses in terms of effectiveness and safety, and we think that because the 81 mg dose had better long-term adherence, it may be the best choice for patients.”

For years, debate has raged around the appropriateness of different aspirin doses in various patient populations, which was the impetus behind creating the ADAPTABLE study. Presented at the American College of Cardiology’s 70th Annual Scientific Sessions (ACC.21), the study enrolled 15,076 patients with existing cardiovascular disease from 40 medical centers across the US.

An open-label, pragmatic trial led by the Duke Clinical Research Institute, ADAPTABLE employed a unique design by allowed patients to enroll and randomize themselves using a secure website, which was also used to record data related to follow-up every 3 or 6 months. Recruitment for the trial begin in April 2016 and ended in June 2019, during this period 50,245 patients visited the website, 32,164 entered a personalized access code, and 15,076 were enrolled and underwent randomization.

Of the 15,076 who underwent randomization, 13,357 reported taking aspirin prior to enrollment and 85.3% of these patients were taking 81 mg of aspirin. In total, 7540 were randomized to 81 mg aspirin and 7536 were randomized to 325 mg aspirin. Of note, the median follow-up of patients included in the study was 26.2 (IQR, 19.0-34.9) months.

The primary effectiveness outcome of the study was a composite outcome defined as death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, which was assessed in a time-to-event analysis. The primary safety outcome of the study was hospitalization for major bleeding, which was also assessed in a time-to-event analysis.

Upon completion of the trial, results suggested the primary effectiveness outcome occurred in 7.28% (n=590) of patients taking 81 mg aspirin daily compared to 7.51% (n=569) of patients taking 325 mg aspirin daily (HR, 1.02; 95% CI, 0.91-1.14; P =.75). In safety analysis, results indicated hospitalization for bleeding occurred in 0.63% (n=53) of patients receiving 81 mg aspirin and 0.60% (n=44) of patients in the 325 mg group (HR, 1.18; 95% CI, 0.79-1.77; P =.41).

Further analysis revealed patients in the 325 mg group had a higher incidence of dose switching during the trial, with 41.6% of patients opting to switch to 81 mg compared to just 7.1% of 81 mg aspirin patients opting to switch to 325 mg aspirin. Investigators pointed out rates of disparities in aspirin discontinuation among the study groups, with discontinuation reported by 7.0% of those assigned to 81 mg aspirin and 11.1% of those assigned to 325 mg aspirin. Additionally, patients in the 325 mg group also had fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs 650 days [IQR, 415 to 922]).

“Daily aspirin is an essential part of treatment for most people with heart disease. Patients and clinicians should use the information from the study to have a conversation about the dose of aspirin they prefer,” Jones said.

This study, "Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease,” was presented at ACC.21 and simultaneously published in the New England Journal of Medicine.