Results presented at the American College of Cardiology's 70th Scientific Session show most patients prefer a smaller dose and are more likely to stick with it.
Aspirin is the most common drug used after people have a heart attack, stroke, or bypass surgery, but until now doctors have not had clear evidence whether it’s best to give patients a low dose—the 81-mg “baby aspirin”—or a regular 325-mg dose.
A head-to-head comparison found the lower dose works just fine, as there were no significant differences in cardiovascular or major bleeding events in the 15,076-patient, real-world trial presented today during the 70th American College of Cardiology Scientific Session.
There was, however, better adherence with the low dose, so starting with the baby aspirin may be the best choice for most patients, said Schuyler Jones, MD, assistant professor of medicine at the Duke Clinical Research Institute and lead author of the study, called ADAPTABLE. Results were simultaneously published in the New England Journal of Medicine.1
While many praised the trial’s pragmatic design, it had one big downside: doctors could not stop patients from changing doses, and many did. As a result, a commentator in the Journal questioned how reliable the findings are and whether investigators should have run a pilot that would have revealed this problem.2
But Jones hailed the arrival of a direct comparison. “There really hasn’t been a clear answer about what is the most effective and safe dose of aspirin for these patients. Instead, there have been conflicting findings, with some research suggesting 81 mg may reduce the risk of bleeding, but the higher dose may provide more effective prevention of heart attacks and stroke,” he said in a statement. “These earlier studies have primarily investigated aspirin—either 81- or 325-mg daily dose—compared with placebo.”
The study design combined classic clinical trial elements with electronic health records and claims data, including that of both commercial payers and CMS. Patients took part by mail, email, or phone and enrolled through a secure website that allowed follow-up every 3 to 6 months for a period of just over 2 years (26.2 months), from April 2016 to June 2019. Patients had to have established atherosclerotic cardiovascular disease plus 1 other risk factor; the median age was 67 years. Most patients were White, 9% were Black, 3% were Hispanic, and 1% were Asian. Patient groups were well balanced at the start of the study, with 7540 taking 81-mg and 7536 taking 325-mg daily doses.
However, of the 96% taking aspirin before the study, 85% were taking baby aspirin, and during the study, switching doses was far more common among those randomized to the 325-mg dose (41.6% in this group switched their dose at least once) compared with the 81-mg dose (only 7.1% switched).
“We made every effort to encourage them to stay on their study dose, but nevertheless people felt very strongly about it, so the differential effects of the 2 doses are less clear since dose switching occurred very frequently, especially in the 325-mg group,” Jones said, while noting that many patients in each group stayed on the assigned dose for over a year. Investigators will conduct additional analyses to learn reasons why patients switch doses.
If patients are taking a 325-mg dose of aspirin and tolerating it well, they are likely fine to continue—but those resuming aspirin or starting it for the first time should probably start with the low dose, he said.
Colin Baigent, of Oxford University, was less convinced. “Because switching was not likely to have been at random, bias arising from this degree of crossover could have obscured a true difference in efficacy or safety (or both), and moreover it is also not possible to conclude that the lack of any significant difference between the 2 dose groups implies equivalence of the effects of the doses,” he wrote in the Journal.
Results were as follows:
ADAPTABLE is the first clinical trial to use PCORnet, the National Patient-Centered Clinical Research Network, a partnership of clinical research networks funded by the Patient-Centered Outcomes Research Institute, which funded the study.
While Jones said his team will do more work to tease out why so many patients switched doses, the big winner may be the study's methodology, which won praise from commenters, including Baigent.
Jane Linderbaum, APRN, CNP, FACC; a member of the ACC Annual Scientific Session Program Committee and cardiovascular nurse practitioner; who is an assistant professor of Medicine at the Mayo Clinic, in Rochester, Minnesota, commended Jones and the research team during a press conference on “this patient-centric study.” She predicted the real-world methodology would become more common.
“There's going to be lots of studies looking to learn from what you've done,” Linderbaum said, praising the use of electronic health records and the fact that patients could enroll themselves and manage their own consent process. “This is a great opportunity for a low-cost trial … during a very challenging time in medicine, both for clinicians, certainly, and for patients.”
1. Jones WS, Mulder H, Wruck LM, et al, for the ADAPTABLE Team. Comparative effectiveness of aspiring dosing in cardiovascular disease. N Engl M Med. Published May 15, 2021. doi:10.1056/NEJMoa2102137
2. Baigent C. Pragmatic trials—need for an ADAPTABLE design. N Engl J Med. Published May 15, 2021. doi:10.1056/NEJMe2106430