PHILADELPHIA—Twenty-one percent of patients who are nonresponsive to the most common aspirin dose for secondary stroke prophylaxis are potentially pharmacodynamically resistant, while the remaining 79% of patients may become platelet responsive at a higher aspirin dose, according to research presented at the 66th Annual Meeting of the American Academy of Neurology.
Erica S. Westphal, research associate, and Fran Gengo, PharmD, Director of Neuropharmacology at the Dent Neurologic Institute in Amherst, New York, and colleagues sought to determine whether patients who do not respond to daily 81-mg doses of aspirin are pharmacodynamically resistant or instead are underdosed and therefore pharmacokinetically resistant. No standardized therapeutic method exists for overcoming aspirin resistance in a secondary stroke prophylaxis population.
A total of 102 patients were platelet nonresponsive to 81 mg of aspirin. All patients had been taking aspirin daily for a minimum of two weeks and had detectable salicylate metabolites in their urine at the time of testing, which indicated compliance. The researchers determined platelet responsiveness with whole blood impedance platelet aggregation using collagen 1 μg/mL and arachidonate 0.5 mM as agonists. The investigators defined platelet nonresponsiveness as a level greater than 10 ohms of resistance to collagen 1 μg/mL and/or an ohms ratio of collagen 1 μg/mL to collagen 5 μg/mL greater than 0.5 and/or greater than 6 ohms to arachidonate.
Participants who were platelet nonresponsive were given an increased dose of aspirin as part of their care. All patients were retested at least two weeks after their aspirin dose had been changed.
Of the 102 patients who were initially platelet nonresponsive to 81 mg of aspirin, 57 (56%) met sensitivity criteria with 162 mg of aspirin, and 29 patients remained resistant. The aggregation response to collagen and arachidonate was statistically less in patients who became responsive to higher doses of aspirin.
Of the 29 patients who remained nonresponsive or partially responsive to 162 mg of aspirin, 10 became responsive on a dose greater than 162 mg, and nine patients remained resistant. Of the 16 patients who had a direct increase from 81 mg of aspirin to a dose greater than 162 mg, 14 patients became sensitive and two remained resistant.
—Colby Stong