Further Ex Vivo Evidence Supporting Higher Aspirin Dosing in Patients With Coronary Artery Disease and Diabetes

Aspirin remains the cornerstone antiplatelet agent for primary and secondary prevention in patients with diabetes mellitus (DM), a disease associated with heightened platelet reactivity, endothelial dysfunction, and inflammation.1,2 Patients with DM are at a greater risk of death, myocardial infarction, and stroke resulting from thrombotic event occurrence than are patients without diabetes. Because reactive platelets play a central role in the genesis of thrombotic events, the antiplatelet effects of various antiplatelet therapy regimens have been a focus of ex vivo investigations in this high-risk population. The current guidelines recommend aspirin (75 to 162 mg QD) for primary prevention in men aged >50 years and women aged >60 years with diabetes at increased cardiovascular risk (10-year risk >10%). Despite these recommendations, the clinical efficacy of the widely used low-dose aspirin regimen (75 to 81 mg QD) to treat the patient with diabetes remains a major source of controversy, and the optimal dose is unknown.3Article see p 180Previous investigations have examined the dose-related effects of aspirin on platelet reactivity. In stable patients with coronary artery disease (CAD), low-dose aspirin did not inhibit platelet function in a significant number, despite highly effective blockade of its primary platelet target cyclooxygenase-1 (COX-1).4,5 The ASPECT (Aspirin-Induced Platelet Effect) study, a double-blind, double-crossover, William design investigation of 81, 162, and 325 mg QD aspirin administered as single doses for 4 weeks, each over a 12-week period, was the largest serial pharmacodynamic investigation of the dose-related effects of aspirin on platelet function in patients with CAD.4 It was clearly demonstrated in the ASPECT study that aspirin inhibited platelet aggregation stimulated by agonists other than arachidonic acid in a dose-dependent manner; significant effects were observed for collagen- and shear-induced aggregation …