Source: Pharmacotherapy  |  Posted 4 years ago

By Danny Kucharsky

NEW ORLEANS, LA -- March 28, 2007 -- Low-dose aspirin may not provide adequate platelet inhibition in diabetic patients, according to results of a study presented here at the 56[^]th[] annual scientific session of the American College of Cardiology (ACC).

The double-blind, double crossover study presented on March 26[^]th[], aimed to determine the effects of 3 doses of aspirin on platelet aggregation in diabetics and nondiabetics.

According to lead investigator Dr. Paul Gurbel, MD, director, Sinai Centre for Thrombosis Research, Baltimore, Maryland, United States, the optimal dose of aspirin to prevent heart attacks in patients with diabetes has never been studied.

In the study, 120 patients (30 with diabetes) with stable coronary artery disease were randomly assigned to receive progressive aspirin doses of 81 mg (low dose), 162 mg, or 325 mg of daily for 4 weeks each, for a total of 12 weeks.

Platelet aggregation was evaluated extensively at the end of each 4-week period. Responses to aspirin were measured by cyclooxygenase 1 (COX-1)-specific assays and COX-1 nonspecific assays.

The overall prevalence of aspirin resistance was below 5% during the 81 mg aspirin treatment period using direct measurement of COX-1 inhibition. Resistance at 81 mg was much higher in diabetic patients when measured by indirect measurements of COX-1, including the levels of adenosine diphosphate (ADP; 27% in diabetics vs 14% in nondiabetics, []P[] = .052), collagen-induced aggregation (27% vs 4%, []P[] = .002), point-of-care VerifyNow aspirin assay (13% vs. 3%, []P[] = .02) and urinary thromboxane levels (37% vs. 17%, []P[] = .02).

Dr. Gurbel noted that "in general, increasing the dose of aspirin in the diabetic patient reduces the prevalence of resistance to a level observed in the nondiabetic patient." At a 325 mg daily dose, for example, collagen-induced platelet aggregation fell significantly, from 54% to 29% among diabetics ([]P[] < .001).

However, Dr. Gurbel said the researchers did not observe a dose-dependent effect of aspirin in ADP-induced aggregation in diabetic patients. This suggests a potential benefit of using ADP-receptor blockers in addition to higher-dose aspirin in selected diabetic patients.

Future large scale studies are needed to evaluate the clinical efficacy of higher aspirin doses in diabetic patients and the impact of diabetes and other variables on the responsiveness of platelets to aspirin and accurate dosing, said Dr. Gurbel.

[Presentation title: Effects of Diabetes on the Prevalence of Aspirin Resistance During Low Dose Aspirin Therapy. Abstract 1019-179]