The continuous challenge of antithrombotic strategies in diabetes: focus on direct oral anticoagulants

Direct oral anticoagulants (DOACs) include dabigatran, which inhibits thrombin, and apixaban, edoxaban, and rivaroxaban, which inhibit factor Xa. They have been extensively studied in large trials involving patients affected by the most common cardiovascular diseases. As the presence of diabetes leads to peculiar changes in primary and secondary hemostasis, in this review we highlight the current evidence regarding DOAC use in diabetic patients included in the majority of recently conducted studies. Overall, in trials involving patients with atrial fibrillation, data seem to confirm at least a similar efficacy and safety of DOACs compared to warfarin in patients with or without diabetes. Furthermore, in diabetic patients, treatment with DOACs is associated with a significant relative reduction in vascular death compared to warfarin. In trials enrolling patients undergoing percutaneous coronary intervention, results concerning bleeding events are consistent in patients with or without diabetes. With regards to the COMPASS study, in patients with diabetes (n = 10,241), addition of rivaroxaban 2.5 mg to aspirin resulted in a significantly lower incidence of major adverse cardiovascular events (HR 0.74, 95% CI 0.61-0.90; interaction p = 0.68) with higher rates of major bleeding expected (HR 1.70, 95% CI 1.25-2.31). The 3287 patients with peripheral artery disease and diabetes receiving rivaroxaban plus aspirin had a twofold higher absolute reduction in the composite endpoint (cardiovascular death, myocardial infarction, and stroke) than patients without diabetes. Finally, we report the involvement of cytochromes or P-glycoprotein on the metabolism of the most commonly prescribed glucose-lowering drugs. No clinically relevant interactions are expected during the concomitant use of DOACs and anti-diabetic agents.