Antiplatelet Therapy in Diabetes: Efficacy and Limitations of Current Treatment Strategies and Future Directions

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality in patients with diabetes (1). The concomitant presence of multiple classical cardiovascular risk factors in diabetic subjects contributes to enhanced atherothrombotic risk (2). However, other risk factors may be important such as abnormal platelet function (3). Platelets, in fact, play a key role in atherogenesis, and its thrombotic complications and measures, which lead to blockade of one or multiple pathways modulating platelet activation and aggregation processes, are pivotal in reducing ischemic risk in diabetic subjects (4). This article reviews currently available antiplatelet agents on ischemic events in diabetic patients, limitations of currently available treatment strategies, and antiplatelet agents currently under clinical development that may potentially overcome these limitations. ### Antiplatelet therapy There are three different classes of platelet-inhibiting drugs: cyclooxygenase-1 (COX-1) inhibitors (aspirin), ADP P2Y12 receptor antagonists (thienopyridines), and platelet glycoprotein (GP) IIb/IIIa inhibitors, which are mostly used for the prevention and treatment of atherothrombotic disorders (4) (Fig. 1). Aspirin inhibits the COX-1 enzyme and therefore blocks platelet thromboxane A2 synthesis (5). However, patients on aspirin therapy, particularly those at high risk, may continue to have recurrent thrombotic events. GP IIb/IIIa inhibitors are very potent antiplatelet agents, which exert effects through inhibition of the final common pathway that mediates platelet aggregation processes, and have been shown to be effective in preventing thrombotic complications in high-risk patients undergoing percutaneous coronary interventions (PCI) (4). However, these agents are available only for parenteral use and have a short duration of action, which impedes their use for long-term protection. The need for alternative antiplatelet treatment strategies led to the evaluation of effects obtained from a combination of oral antiplatelet agents inhibiting other platelet-activating pathways. Ticlopidine is a first-generation thienopyridine, which irreversibly blocks the platelet ADP P2Y12 receptor (6). Its combination with aspirin is associated …