In May 2021, the New England Journal of Medicine published the results of the ADAPTABLE, which were also presented at the virtual American College of Cardiology (ACC) 2021 Scientific Session. The main purpose of the study was to determinate the appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease which is still a subject of controversy. Despite acetylsalicylic acid has been established as an appropriate long-term medication for patients with ischemic heart disease since the 1980s, there is still no reliable information on the correct dose. The US guidelines suggest any dose in the range of 81 mg to 325 mg daily can be used, whereas the European guidelines recommend 81 mg daily, although this is mainly based on observational data and expert opinion; there is little hard, randomized-trial evidence.
The ADAPTABLE trial randomly assigned 15,076 patients established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. Before randomization, 96% of those with available information were already taking aspirin, 85% of whom were taking 81 mg. After a mean follow-up of 26 months, the primary efficacy endpoint — a composite of all-cause death, myocardial infarction (MI), or stroke — had occurred in 7.28% of the 81-mg group and 7.51% of the 325-mg group (hazard ratio [HR], 1.02; 95% CI, 0.91 - 1.14). The primary safety outcome, hospitalization for major bleeding with an associated blood transfusion, occurred in 0.63% of the 81-mg group and 0.60% of the 325-mg group (HR, 1.18; 95% CI, 0.79-1.77). Patients assigned to 325 mg had a higher incidence of dose switching (41.6%) than those assigned to 81 mg (7.1%) and were more likely to discontinue treatment (11.1% vs 7.0%). This resulted in fewer median days of exposure to the assigned dose in the 325-mg group (434 vs 650 days). A sensitivity analysis based on which dose the patient actually reported taking showed a higher risk for death, MI, or stroke in patients who took 81 mg than those who took 325 mg (HR, 1.25; 95% CI, 1.10 - 1.43).
Given the substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily, the results support the approach of starting new patients on 81 mg. Nevertheless, patients who have tolerated 325 mg long term may want to stay on this dose as it may be associated with moderate benefit.
Reference: The New England Journal of Medicine May 15, 2021
DOI: 10.1056/NEJMoa2102137
