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Antiplatelet Agents in Diabetic Patients: Clinical Advances and Remaining Questions

Pierre Sabouret, Magali Taiel-Sartral, Jean-Philippe Kevorkian, Bruno Vergès

Patients with diabetes mellitus (DM) are at significantly greater risk for major cardiovascular events (MACE) than non-DM patients. Primary and secondary prevention of cardiovascular disease (CVD) involves a multifactorial approach that aims to treat the cluster of risk factors associated with this condition including blood disorders and clinical features, such as hyperglycaemia, dyslipidemia, hypercoagulation, obesity and hypertension.

Platelet activation and aggregability play a key role in the genesis of arterial thrombus secondary to plaque rupture. For patients in secondary prevention, inhibition of platelet function is crucial to significantly decrease the rate of MACE. Inhibiting plaque rupture would therefore prevent platelet aggregation.

For patients with DM presenting with an acute coronary syndrome (ACS), a dual antiplatelet therapy with antagonism of COX1 and P2Y12 is central to their treatment, especially in the setting of percutaneous coronary intervention (PCI) and stenting. Large randomized trials have demonstrated that platelet inhibition with the P2Y12 antagonist clopidogrel, is associated with a better short and long-term prognosis after an acute coronary syndrome. Despite the clinical benefits of clopidogrel in patients with ACS, it has limitations in urgent and early PCI due to its slow onset of action, large interindividual variability and drug-drug interactions resulting in inconsistent drug response with reduced efficacy, especially in patients with diabetes. Therefore, newer drugs with a rapid onset of action, and a more potent and predictable effect have been developed. Prasugrel and ticagrelor have demonstrated net clinical benefit over clopidogrel in two major randomized trials, including a large number of diabetic patients, in patients presenting with non-ST elevation ACS (NSTE-ACS) and ST-elevation ACS (STE-ACS) revascularized by PCI. The aim of this review is to provide an overview of aspirin, P2Y12 receptor antagonists, and Glycoprotein (GP) IIb-IIIa inhibitors in the management of diabetic patients, with a focus on perspectives in optimal and appropriate agent selection and timing of treatment in both primary and secondary prevention.