Platelet Sensitivity to Aspirin Declines Over Time

Prolonged treatment with aspirin is associated with a progressive reduction in antiplatelet activity, physicians in Rome report. But the same is not true for prolonged treatment with ticlopidine.

Previous research has suggested a progressive decrease in aspirin’s clinical efficacy after 2 years of treatment, Dr. Fabio M. Pulcinelli and his associates explain in the Journal of the American College of Cardiology for March 17. To explore the underlying mechanism, the research team at the University “La Sapienza” monitored patient blood samples for 2 years following initiation of antiplatelet treatment.

In a cohort of 150 patients with evidence of atherothrombosis, the maximal percentage of platelet aggregation in response to collagen decreased from 88.2% at baseline to 37.9% after 2 months. Repeat testing revealed a progressive increase, to 46.1% at 6 months, 48.2% at 12 months and 61.9% at 24 months. The 24-month measurement was significantly higher than that observed at 2 months.

Sensitivity to the agonist ADP was also reduced during follow-up, although the effect was less pronounced. Results were not affected by aspirin dosage (100 mg or 330 mg daily) or by presence of hypertension or hypercholesterolemia.

In a group of 80 patients matched for gender, age and risk factors, antiplatelet inhibition in response to treatment with ticlopidine did not change significantly during 2 years of treatment.

Other researchers have observed a reduction in cardiovascular events when treatment with aspirin was combined with clopidogrel, another antiplatelet agent.

“Future studies should therefore address the question of whether the superiority of such a combination is dependent on a more complete and efficient inhibition of platelet aggregation or on a protective effect provided by clopidogrel in patients with a progressively reduced sensitivity to aspirin,” Dr. Pulcinelli’s team concludes.

J Am Coll Cardiol 2004;43:979-984.