Aspirin Nonresponsiveness Variable, Unpredictable
The wide variability of measurements of nonresponsiveness to aspirin therapy has important clinical implications. Future studies should aim to determine an accurate measurement of aspirin resistance and answer the question of how to treat patients who do not respond to aspirin therapy.
Reports of aspirin resistance have risen in the past decade, as newer and presumably better measures of aspirin resistance have emerged, according to Steven R. Steinhubl, MD, Associate Professor of Medicine at the University of Kentucky. Measurements using thromboelustography, urinary thromboxane, flow cytometry, light transmission-aggregometry and PFA-100 predict that from 0.5% to 75% of the population is resistant to aspirin therapy, he said.
Add or Increase?
Steinhubl raised doubts about adding clopidogrel or increasing the dose of aspirin in nonresponders. The benefit of either strategy may be related to the patient population in question or other factors that have not yet been identified, he said.
“There is compelling evidence that in some populations, the addition of clopidogrel to aspirin improved clinical outcomes, most notably in the CURE trial,” he said. CURE suggested that 20% of the population is resistant to aspirin therapy and would benefit from the addition of clopidogrel.
The increase in risk for coronary events in patients given placebo compared with patients given clopidogrel can be explained by the population that participated in the trial, according to Steinhubl. CURE’s focus was on patients with acute coronary syndromes, and evidence from the trial may not be easily extrapolated to other patient groups, Steinhubl said.
In the CHARISMA trial, for instance, the addition of clopidogrel for aspirin nonresponders did not have a beneficial effect and “actually showed a trend toward harm,” Steinhubl said.
The benefits of increasing the aspirin dose is also questionable. In a study by P-Y Lee from the University of Hong Kong, using the VerifyNow (Accumetrics) assay, all patients on 300 mg of aspirin responded. According to a study by Mark J. Alberts, MD, from Northwestern University in Chicago, 72% of patients on 325 mg of aspirin responded to therapy.
Similarly, no meta-analyses have shown thus far even a trend toward a benefit with higher-dose aspirin and “in fact almost every trial that has compared head-to-head different doses of aspirin has shown a benefit favoring the lower dose of aspirin,” Steinhubl said.
