![]() ![]() ![]() a lower dose of aspirin, consistently with saturability of platelet thrombox- ane inhibition at low doses.5 The ADAPTABLE results are in line with previous knowledge about dose requirements for a full antith- rombotic effect of aspirin,6 and coherent with lack of evidence for a non-platelet mediated mechanism of action (e.g., anti-inflammatory) contributing to clinical efficacy. In fact, previous indirect3 as well as direct4 dose comparisons failed to show superiority of a higher dose vs. 81 mg of as- pirin makes the apparent equipoise between the two largely unsur- prising. ![]() While a streamlined design with greatly reduced costs is a welcome in- novation for a large, independent randomized clinical trial in the USA, lack of a pilot feasibility study and/or a pre-randomization run-in period to test tolerability of the study medications is a major weakness of the ADAPTABLE trial,1 as pointed out by Colin Baigent in the accompany- ing Editorial.2 Although asymmetrical dose switching may have biased the results toward the null, lack of a pharmacologically plausible hypothesis to justify the expected superiority of 325 vs. However, aspirin discontinuation was reported by 7% of the patients assigned to the 81-mg group and 11% of those assigned to the 325-mg group, and dose switching was reported by 7% in the 81-mg group and 42% in the 325-mg group. No heterogeneity in treatment effect was apparent among 8 prespecified sub-groups. Interestingly, all-cause death occurred in 315 patients (estimate at me- dian follow-up, 3.8%) in the 81-mg group and 357 patients (estimate at median follow-up, 4.4%) in the 325-mg group (HR, 0.87 95% CI, 0.75–1.01), with time-to-event curves progressively diverging after 6 months. During a median 26-month follow-up, there were no statistically significant differences between the two aspirin doses, either in the risk of the primary effectiveness endpoint or in the risk of hospitalization for major bleeding (estimated percentage, 0.63% in the 81-mg group and 0.60% in the 325-mg group HR, 1.18 95% CI, 0.79–1.77).The vast majority reported that they had been taking aspirin before enrolling in the trial of these patients, 85% and 12% reported taking 81 and 325 mg, respectively. About one-third had previous MI, and one-half had previous coronary revascularization proce- dures. Over 3 years, 15 076 patients (median age, 68 years) were recruited and randomly assigned in a 1:1 ra- tio to take 325 or 81 mg of aspirin daily. Patients with established ASCVD were identified with the use of electronic health record data at each institution moreover, to streamline procedures and reduce costs, patients were instructed to access a Web portal to give informed consent and be notified of their aspirin reg- imen (which they were asked to purchase themselves) and all trial visits were done virtually or by telephone, with outcomes ascertained remotely and without adjudication.(ASCVD).1 The primary safety outcome was hospitalization for major bleeding with an associated blood-product transfusion. ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness), an open-label, pragmatic, random- ized, controlled trial, funded by the Patient-Centered Outcomes Research Institute, was designed to test the hypothesis that a higher aspirin dose (325 mg daily) would result in a lower risk of death from any cause, hospitalization for myocardial infarction (MI), or hospitalization for stroke (primary effectiveness endpoint) than a lower dose (81 mg daily) among patients with atherosclerotic cardiovascular disease.The results of ‘Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease’ have been published in the New England Journal of Medicine. Gemelli 8, 00168, Rome, Italy and Department of Pharmacology, Fondazione Policlinico Gemelli-IRCCS, Catholic University School of Medicine, Largo F. Department of Cardiovascular and Pulmonary Sciences, Fondazione Policlinico Gemelli-IRCCS, Catholic University School of Medicine, Largo A.
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