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Too many study volunteers randomized to the 325-mg dose switched to the 81-mg one to settle the dosage issue But ADAPTABLE is still being celebrated as the kind of "pragmatic study'' that can be a less expensive, more realistic version of the RCT.
A large, innovative study designed to settle the long-festering issue about the preferred aspirin dose for people with established cardiovascular disease likely didn’t end the debate as hoped because so many of the people randomized to take the higher dose of aspirin switched to the lower one, according to results presented today at the American College of Cardiology’s annual meeting.
Results from the ADAPTABLE study showed no significant difference in the effectiveness or safety outcomes between taking an 81-milligram (mg) dose of aspirin daily or a 325-mg dose for secondary prevention of cardiovascular disease.
However, the true meaning of that tie in effectiveness and safety was clouded by the fact that 41.6% (2,963 of 7,130) of those assigned to the 325-mg dose switched to the 81-mg dose. A much smaller proportion (7%) of the volunteers switched in the other direction, from the 81-mg to the 325-mg one.
The study was published simultaneously in The New England Journal of Medicine, and the researchers said in the study published in the journal that further analysis showed that patients who continued to take the 325-mg dose had a lower rate of cardiovascular events, but they also cautioned against making too much of that result because of the biases inherent in that kind of analysis.
People with established cardiovascular disease are supposed to take a daily aspirin to prevent another heart attack and other cardiovascular events because aspirin helps make platelets less “sticky” and therefore blood less likely to clot and cause an obstruction in arteries supplying the heart and brain. But secondary prevention guidelines — notably those issued jointly by the American College of Cardiology and the American Heart Association — do not provide definitive guidance about the size of the dose. Research results have been mixed and haven’t sent that strong, conclusive signal about which dose would be best for most people.
Results from the ADAPTABLE study were widely anticipated because they might have added the evidence needed to settle the dosage question, but also because ADAPTABLE is an example of the kind of “pragmatic” study that researchers hope can tackle clinical issues in a way that is far less expensive than the traditional randomized clinical trial and in circumstances of actual “real world” clinical practice.
Funded by a grant from the Patient-Centered Outcomes Research Institute (PCORI), the ADAPTABLE study design included innovations such as identifying volunteers with algorithms that searched through electronic health records and using patient portals to have the study volunteers give informed consent. The researchers were advised by nine “patient-partners” about the study’s protocol and any materials and explanations they gave to patients. ADAPTABLE was the first clinical trial to use the National Patient-Centered Clinical Research Network (PCORnet), a PCORI-funded data center that enables pragmatic studies.
An accompanying editorial in NEJM by Colin Baigent, F. Med. Sci., heralded the ADAPTABLE results as providing proof of principle that large, pragmatic, randomized trials can be conducted in the U.S. as they have been in other countries. But Baigent also said a pilot study might have helped the researchers identify the switching problem and alter the study’s design.