Ibuprofen Makes Aspirin Moot for Stroke Patients

By Michael Smith
BUFFALO, N.Y., March 13 -- For secondary stroke prophylaxis, ibuprofen nearly cancels out the antiplatelet benefit of aspirin, researchers here said.
The combination markedly reduces aspirin's antiplatelet effect to the point that patients taking both may have essentially normal platelet aggregation for up to 20 hours a day, according to Francis Gengo, PharmD, of the University of Buffalo, and colleagues.
Taking both drugs together "can have clinical consequences for patients taking aspirin," Dr. Gengo and colleagues reported previously in the January issue of the Journal of Clinical Pharmacology.
Indeed, a second study, reported in the March issue of the journal, found that among patients who had a recurrent cerebral ischemic event, 66% were non-responsive to aspirin.
Dr. Gengo and colleagues found that taking a non-selective non-steroidal anti-inflammatory drug along with aspirin significantly increased the odds (P=0.001) of a recurrent event.
The implication, Dr. Gengo said, is that "whatever number of patients who have had strokes because of the interaction between aspirin and NSAIDs, those strokes were preventable."
The problem is that aspirin irreversibly binds the Cox-1 enzyme and renders a platelet unable to aggregate. NSAIDs also bind the enzyme, but their effects are reversible, Dr. Gengo and colleagues noted.
Competition between the drugs can inhibit the effect of aspirin, the researchers showed in the earlier study, which combined a pharmacological analysis of drug interactions in 10 healthy volunteers, with a similar examination of 18 patients who were taking prophylactic aspirin and a concomitant NSAID.
In a crossover study, the healthy volunteers were given 400 mg of ibuprofen, 325 mg of aspirin, and ibuprofen followed by aspirin two hours later.
The study found that two hours after taking aspirin alone, platelet aggregation was inhibited by 76% to 91%, depending on the measuring technique used, and platelet function only returned to baseline values between 72 and 96 hours later.
In contrast, ibuprofen alone reduced aggregation by 33% to 45% and platelet aggregation was essentially normal within about five hours.
When the two drugs were taken together, the effect of aspirin was significantly reduced (P<0.007) and the average time for platelet aggregation to return to baseline values was again about five hours.
Among the 18 patients taking both drugs, there was no significant inhibition of platelet aggregation, the researchers said. However, when the patients stopped the NSAID and returned for testing, the effect of aspirin was restored, Dr. Gengo and colleagues found.
Interestingly, 13 of the 18 were being treated because of a recurrent cerebrovascular event. Dr. Gengo and colleagues said the ischemic events might have occurred regardless of the NSAID use.
"However, the likelihood that 13 of 18 patients taking aspirin and NSAIDs, with none showing inhibition of platelet aggregation, would by chance alone have another ischemic event seems remote," they said.
The researchers did not report any outside funding for the studies. Dr. Gengo reported no conflicts.
Primary source: Journal of Clinical PharmacologySource reference:Gengo FM, et al "Prevalence of platelet nonresponsiveness to aspirin in patients treated for secondary stroke prophylaxis and in patients with recurrent ischemic events" J Clin Pharmacol 2008; 48: 335-343. Additional source: Journal of Clinical PharmacologySource reference: Gengo FM, et al "Effects of ibuprofen on the magnitude and duration of aspirin's inhibition of platelet aggregation: clinical consequences in stroke prophylaxis" J Clin Pharmacol 2008; 48: 117.