An enteric coating did not hurt the effectiveness of aspirin pills for secondary prevention of atherosclerotic cardiovascular disease (ASCVD), but it didn’t make it any safer either, researchers found in the ADAPTABLE trial.
Between enteric-coated and uncoated aspirin users, there was no difference in the combined incidence of myocardial infarction, stroke, or all-cause death over a median 26.2 months of follow-up (adjusted HR 0.94, 95% CI 0.80-1.09), reported Mark Effron, MD, of John Ochsner Heart and Vascular Institute at the University of Queensland-Ochsner Clinical School in New Orleans, and colleagues.
Major bleeding events, namely hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage, were similarly likely between groups as well (adjusted HR 0.82, 95% CI 0.49-1.37), the study authors showed in JAMA Cardiology.
“While prior pharmacodynamic studies have found that enteric coating impedes the temporal dissolution of the aspirin in the small intestine and limits overall drug absorption, the results of the present study suggest no clear differences in clinical outcomes and should promote further discussion about the appropriate formulation and dose for individual patients,” Effron’s group concluded.
An enteric coating, also known commercially as “safety coating,” is thought to decrease gastrointestinal (GI) bleeding from aspirin — a concept that the investigators said their post hoc secondary analysis of ADAPTABLE does not totally disprove.
Effron and colleagues noted that they did not assess minor GI tract or other bleeding. Moreover, they acknowledged that they could not track whether ADAPTABLE participants adhered to their reported initial aspirin formulation, nor whether they switched formulations during the trial.
Historically, “it has been recommended for patients to use enteric-coated aspirin over the plain pressed uncoated formulations to minimize GI tract ulceration and bleeding, but to our knowledge, no study has shown that the enteric-coated formulation is safer than uncoated aspirin,” the group wrote.
Effron and colleagues reported that coadministration of acid-reducing medication with enteric-coated aspirin did not change ischemic or bleeding rates in the study.
“More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve ischemic and bleeding outcomes among patients with ASCVD,” they urged.
ADAPTABLE was an open-label, multicenter trial originally designed to test low- versus high-dose aspirin (81 vs 325 mg daily) in people with ASCVD. The main results showed no between-group differences in the primary safety and effectiveness endpoints.
For their secondary analysis, Effron’s group relied on the 10,678 participants — almost all already using aspirin of some kind before entering the trial — who self-reported the aspirin formulation they chose for the study.
Median age was 68 years, 68% were men, and 84% were white. The proportions self-reporting use of enteric-coated aspirin versus uncoated aspirin were 69% and 31%, respectively.
Regardless of the coating of each pill, aspirin dose once again showed no association with effectiveness or safety in the secondary analysis.
The study authors warned that the present report should be treated as observational despite the randomized nature of the larger ADAPTABLE trial.
“Because the participants decided which formulation of aspirin they would use, there may be unknown confounders leading to the choice of aspirin formulation used by the participant,” Effron and colleagues noted.
“For instance, a well-known leading brand of aspirin has a large number of their aspirin products, particularly cardiovascular products, packaged with the phrase ‘safety coating’ included,” they added.
The study was supported by the Patient-Centered Outcomes Research Institute.
Effron reported receiving personal fees, holding stock, and receiving a pension from Eli Lilly. Co-authors reported multiple relationships with industry.
Source Reference: Sleem A, et al “Effectiveness and safety of enteric-coated vs uncoated aspirin in patients with cardiovascular disease: a secondary analysis of the ADAPTABLE randomized clinical trial” JAMA Cardiol 2023; DOI: 10.1001/jamacardio.2023.3364.