Cardiovascular Disease

Loren Bonner

Results of a new pragmatic trial called ADAPTABLE will give clinicians and their patients with heart disease more to discuss when it comes to the right dose of aspirin needed to prevent another heart attack or stroke.

Researchers evaluated aspirin taken at 81 mg per day compared with 325 mg per day among patients with established atherosclerotic cardiovascular disease (ASCVD).

The study findings, which were published on May 27, 2021, in the New England Journal of Medicine, failed to show that aspirin 325 mg was superior to 81 mg in patients with ASCVD.

“This clinical question has vexed many of my fellow clinical pharmacists from the days we learned about cardioprotection of aspirin therapy in school,” said Kevin Haynes, PharmD, from the clinical research organization HealthCore, which helped recruit patients for the study.

Aspirin is recommended for the primary prevention of CVD for high-risk patients, but there has been long-standing debate over the best dosage of this commonly used medication, especially since aspirin is purchased over the counter.

“This trial advances the evidence on this clinical question as we assist patients in the aisles of our stores in navigating the discussion with their doctors about the right dose,” said Haynes.

Study details

“Studying over-the-counter drugs has always been a challenge and the pragmatic recruitment and patient engagement in a trial like ADAPTABLE sets the stage for what is possible in large pragmatic clinical trials,” said Haynes.

The ADAPTABLE trial was a virtual trial involving 15,076 participants with established ASCVD. Patients were randomly assigned 81 mg or 325 mg of aspirin per day and followed for approximately 2 years.

Researchers found no differences in rates of death, hospitalization for a heart attack or stroke, and bleeding between participants who took 81 mg and those who took 325 mg per day.

The primary effectiveness outcome, assessed in a time-to-event analysis, was a composite of death from any cause; hospitalization for myocardial infarction; or hospitalization for stroke. The primary safety outcome was hospitalization for major bleeding.

Overall, there were differences in these endpoints, but also differences in study dose adherence.

Dose switching and discontinuation

Over the course of the trial, the research team found that participants who were assigned to 325 mg of aspirin per day were more likely to switch doses or stop taking aspirin than people assigned to 81 mg per day (42% vs. 7%, respectively). This dose switching and discontinuation may have affected the results, said W. Schuyler Jones, MD, lead author of the study.

“The fact that patients who didn’t switch aspirin doses during the study had better outcomes was interesting,” said Jones, who is an interventional cardiologist at Duke University Health System.

“Possibly, there were medical reasons for switching aspirin dose—such as atrial fibrillation, cancer diagnosis, or percutaneous coronary intervention,” he continued.

Schuyler said he thinks the primary take-away message is that 81 mg per day is the appropriate dose for most patients with established heart disease.

“But those patients who have tolerated 325 mg over time should speak to their clinicians about staying on that dose,” he said.

People with heart disease should discuss the following aspirin dosing guidelines with their clinicians:

• If you are on 81 mg now, staying on that dose is probably right since no differences were found between the two doses.
• If you are resuming aspirin, starting a lower dose (81 mg) is probably right due to better tolerability. There is no conclusive evidence that a higher dose is better.
• If you are on 325 mg now and doing okay, consider staying on that dose.

Source: theaspirinstudy.org/