Higher prevalence of aspirin resistance in patients with diabetes

March 24, 2007

More patients with diabetes are resistant to the platelet-inhibiting effects of low-dose aspirin than patients without diabetes. Therefore, patients with diabetes may benefit from higher aspirin doses for cardioprotection, Paul A. Gurbel, MD, said.

More patients with diabetes are resistant to the platelet-inhibiting effects of low-dose aspirin than patients without diabetes. Therefore, patients with diabetes may benefit from higher aspirin doses for cardioprotection, Paul A. Gurbel, MD, pictured right, said at the 2007 American College of Cardiology annual scientific session.

In a double-blind, double crossover study, Dr. Gurbel studied the effects of three doses of aspirin on platelet aggregation in 30 diabetics and 90 nondiabetics with a history of coronary artery disease (CAD). The patients were treated with aspirin at doses of 81 mg, 162 mg, and 325 mg daily for 4 weeks each.

Platelet aggregation was measured at the end of each 4-week period using four methods that directly and indirectly measure inhibition of cyclooxygenase-1 (COX-1).

The prevalence of aspirin resistance using direct measurement of COX-1 inhibition was low (

Among patients with diabetes, resistance decreased as the aspirin dose increased, such that at 325 mg/d there was no overall difference in platelet aggregation between the patients with diabetes and those without diabetes. There was, however, no dose-dependent effect of aspirin on ADP-induced aggregation in diabetic patients.

The greater efficacy of higher doses of aspirin in inhibiting platelets in the diabetics suggests that "the antiplatelet effect of aspirin is not solely mediated by inhibition of COX-1," said Dr. Gurbel, director, Sinai Center for Thrombosis Research, Sinai Hospital, and associate professor of medicine, Johns Hopkins University, Baltimore. "You see a dose-dependent effect of aspirin on inhibiting platelet aggregation even after COX-1 is maximally blocked."

The clinical practice of a "one size fits all" approach to prescribing aspirin therapy should be modified, he added. "If platelet aggregation is a cardiovascular risk factor, why aren’t we measuring it?" he said.

The lack of a greater effect of higher doses of aspirin on ADP-induced platelet aggregation in the diabetics suggests that some patients with diabetes may benefit from using an ADP receptor blocker in addition to a higher dose of aspirin.