Rationale and Design of the Aspirin Dosing—A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial

Abstract

BACKGROUNDThe 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 is a subject of controversy. METHODSUsing an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTSA total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONSIn this pragmatic trial involving patients with established cardiovascular disease, there was 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. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.

Characteristics of clinical trials evaluating cardiovascular therapies for Coronavirus Disease 2019 Registered on ClinicalTrials.gov: a cross sectional analysis

“…Integration of research into routine clinical care 30 or established registries 31 focusing on specific disease states, therapies, or patient populations could help establish such infrastructures 32 . Additionally, utilization of adaptive trial designs 33 , real-world data, and technology-based platforms for trial enrollment and execution has the potential to substantially decrease trial costs and complexity 34 . While such trials are often open label, the benefits of efficient evidence generation using these mechanisms may outweigh the potential for bias introduction, especially if efforts are made to transparently acknowledge pertinent trial limitations upon reporting.…”

PCORnet® 2020: current state, accomplishments, and future directions

“…After networks and their sites complete a query against data obtained from patients seen in the past 18 months, they can be reidentified by the health systems (which hold reidentification keys), enabling a variety of techniques for rapidly recruiting participants into trials. This is a unique ability of the PCORnet infrastructure and has been used successfully in ongoing clinical trials, such as ADAPTABLE, which is studying the optimal dosage of aspirin for secondary prevention of ischemic heart disease [17].…”

Precision Medicine in TAVR: How to Select the Right Device for the Right Patient

“…The investigators of the Aspirin Dosing-A Patient-centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) trial capitalized on the availability of electronic health records, online study platforms, and health plan claims to evaluate the comparative effectiveness of 2 doses of aspirin in the secondary prevention of atherosclerotic cardiovascular disease. 10 Isolated European national registries may also be suited to address these questions in future registry-based randomized trials, including the Swedish Web-system for Enhancement and Development of Evidenced-based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDE-HEART) registry and the Western Denmark Heart Registry (WDHR). 11,12 Leveraging national registries to conduct observational studies assessing the real-life safety and comparative effectiveness of different TAVR devices should also be considered, using rigorous, prespecified statistical analysis plans incorporating strategies accounting for practice variations across hospitals and heterogeneity in case-mix.…”