A study designed to tease out genetic factors for drug resistance to aspirin failed to identify even one case of true drug resistance. Instead, researchers reported online Dec. 4 in Circulation, the enteric coating on aspirin appears to lead to delayed or reduced absorption of the drug.
The benefits of low-dose aspirin for reducing the risk of adverse events in patients with cardiovascular disease are well known. But some studies have estimated that up to 28 percent of patients who receive the therapy are aspirin resistant. Tilo Grosser, MD, of the Institute for Translational Medicine and Therapeutics at Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues sought to explore the variance in response to aspirin and estimate the commonality of a specific phenotype that might explain pharmacological resistance to aspirin.
They recruited 400 healthy people for the study, which was carried out in three phases. First, the volunteers ingested a single dose of 325 mg regular immediate-release aspirin (Bayer Health Care) or enteric-coated aspirin (Safety Coated Bayer Aspirin). The researchers used before and after blood and urine tests to measure responses to the drug. Volunteers who appeared to be drug resistant underwent repeat testing. If they failed to respond again, they were given an 81 mg dose of enteric-coated aspirin and 75 mg clopidogrel for one week in a crossover design.
In the first phase, all 40 volunteers who took regular immediate-release aspirin responded to the drug eight hours after dosing. Of those taking enteric-coated aspirin, 150 were assessed at four hours and 210 at eight hours. In the four-hour group, 49 percent were deemed non-responders and in the eight-hour group, 17 percent were considered non-responders. In the next phases, all responded to aspirin through repeated exposure, extended dosing or the addition of aspirin to their platelets ex vivo.
“We found that under acute dosing conditions, the frequency of ‘resistance’ based solely on the failure to suppress the aggregation response to arachidonic acid was conditioned by the formulation of aspirin and the timing of the measurement,” Grosser and colleagues wrote. “‘Resistance' was measurable after enteric-coated, but not immediate-release, formulations of aspirin and appeared more frequent after the former when measurements were performed four hours rather than eight hours after dosing.”
They pointed out that they did not find one case that met their criteria for aspirin resistance that might be attributed to genomic variation or pathways. “By contrast, pseudoresistance, due to delayed and reduced drug absorption was common after ingestion of enteric-coated aspirin,” they concluded. “These observations question the value of seeking to diagnose aspirin resistance with single point-of-care diagnostic approaches and support the finding of inconsistent platelet inhibition following enteric-coated preparations of aspirin.”
The study was funded in part by Bayer Health Care in Morristown, N.J.