Pragmatic Trials — Need for ADAPTABLE Design

This editorial reflects on the ADAPTABLE trial, which evaluated 81 mg versus 325 mg daily aspirin for secondary prevention of cardiovascular disease in over 15,000 patients. Despite innovative and cost-effective trial methods, including digital recruitment via electronic health records, remote consent, and virtual follow-up, no significant difference in efficacy or bleeding risk was found between the two doses. The estimated event rates were 7.28% in the 81-mg group and 7.51% in the 325-mg group for the composite endpoint (death, MI, or stroke), and 0.63% vs. 0.60% for major bleeding. However, the trial was affected by significant treatment crossover: 41.6% in the 325-mg group switched to 81 mg, which may have biased the results and masked true differences. The editorial emphasizes the need for pilot testing and better adherence strategies in pragmatic trial design. ADAPTABLE is nonetheless hailed as a breakthrough in demonstrating how large-scale, low-cost randomized studies can be successfully conducted in the U.S., with implications for broadening clinical inquiry using real-world infrastructure.

This editorial reflects on the ADAPTABLE trial, which evaluated 81 mg versus 325 mg daily aspirin for secondary prevention of cardiovascular disease in over 15,000 patients. Despite innovative and cost-effective trial methods, including digital recruitment via electronic health records, remote consent, and virtual follow-up, no significant difference in efficacy or bleeding risk was found between the two doses. The estimated event rates were 7.28% in the 81-mg group and 7.51% in the 325-mg group for the composite endpoint (death, MI, or stroke), and 0.63% vs. 0.60% for major bleeding. However, the trial was affected by significant treatment crossover: 41.6% in the 325-mg group switched to 81 mg, which may have biased the results and masked true differences. The editorial emphasizes the need for pilot testing and better adherence strategies in pragmatic trial design. ADAPTABLE is nonetheless hailed as a breakthrough in demonstrating how large-scale, low-cost randomized studies can be successfully conducted in the U.S., with implications for broadening clinical inquiry using real-world infrastructure.