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EASD: Twice-Daily Aspirin Betters Platelet Inhibition for People with Diabetes

Posted: Monday, September 19, 2011

Twice-daily aspirin administration, but not a once-daily doubling of the dose, appears to provide good inhibition of platelet cyclooxygenase (COX)-1 in diabetic patients who have rapid recovery of COX-1 activity, and might enhance cardiovascular protection.

Aspirin is currently recommended for cardiovascular protection in patients with type 2 diabetes mellitus, but primary prevention trials have failed to demonstrate its efficacy in this population, possibly because of incomplete platelet inhibition. Researchers, led by Francesco Zaccardi, MD, from the Department of Medicine at Catholic University in Rome, Italy, investigated glycemic control and other factors as possible reasons for incomplete inhibition of thromboxane A2 by low-dose aspirin over 24 hours. Thromboxane A2 is prothrombotic.

The investigators recruited 100 patients with type 2 diabetes who were taking 100 mg of aspirin daily. They measured thromboxane B2, the hydrolysis product of thromboxane A2 and a marker of platelet COX-1 activity, every 3 hours, between 12 and 24 hours after an observed aspirin administration, to assess the kinetics of recovery of COX-1 activity. In addition, a subset of 46 patients had 24-hour continuous glucose monitoring. Of them, the 33 patients with the steepest slopes of recovery of COX-1 activity were randomly assigned to receive aspirin 100 mg daily, 200 mg daily, or 100 mg twice daily for 28 days. Recovery of COX-1 activity was then determined on day 29 during the 12 to 24 hour dosing period.

The researchers found that COX-1 activity showed linear kinetics with large variability among individuals in the slope of recovery of enzyme activity. Independent predictors of the slope of thromboxane B2 recovery were mean platelet volume, higher body mass index, and age. None of the parameters studied in continuous glucose monitoring (e.g., mean 24-hour glycemic value, mean amplitude of glycemic excursions), nor glycated hemoglobin or fasting glucose level, predicted the slope of recovery of thromboxane B2.

In the cohort with the steepest slopes of return of COX-1 activity, the subjects taking 100 mg of aspirin twice daily showed complete normalization of the slope of platelet COX-1 activity; the administration of 200 mg daily did not have such an effect.

The researchers conclude that neither 24-hour glucose control nor other glycemic indices affected the recovery rate of platelet COX-1 activity. They surmised that the interindividual variability in the return of COX-1 activity probably reflects abnormal megakaryopoiesis associated with type 2 diabetes. Twice-daily aspirin administration can overcome the inadequate thromboxane inhibition seen with once-daily dosing.

Source:, European Association for the Study of Diabetes (EASD) 47th Annual Meeting: Abstract 72. Presented September 13, 2011.

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