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Platelets play a central role in the pathogenesis of atherothrombosis.1) Thus, achieving platelet inhibition is an important part of managing patients that have experienced an atherothrombotic event. Dual antiplatelet therapy with clopidogrel plus aspirin has been shown to markedly reduce ischemic events in patients undergoing percutaneous coronary intervention (PCI) and stenting.2) Despite its proven benefit of dual antiplatelet therapy, diabetic patients remain at increased risk of recurrent ischemic events when compared to non-diabetic patients.  Refer to the page 462-466  Recent evidence suggests that diabetic patients are resistant or partially responsive to treatments with a dual antiplatelet effect (especially clopidogrel) which is related to poor clinical outcomes such as stent thrombosis and recurrent atherothrombotic events.3),4) Yang et al.5) previously reported that triple antiplatelet therapy (dual antiplatelet plus cilostazol) results in more potent inhibition of adenosine diphosphase (ADP) induced platelet aggregation than dual antiplatelet therapy in patients with diabetes and drug-eluting stent (DES) implantation. These results suggest that triple antiplatelet therapy is a treatment option for amelioration of low responsiveness to clopidogrel in diabetes mellitus (DM).  No treatments of clopidogrel low responsiveness in DM have been reported to date. An initial approach to clopidogrel low responsiveness was considered to be a correctable cause of resistance, including hyperglycemia, noncompliance, insulin resistance (metabolic syndrome) and drug interaction.  Currently, practical strategies to overcome clopidogrel low responsiveness include 1) addition of cilostazol, 2) increasing the dose of antiplatelet agents, and 3) the use of new drugs, such as prasugrel or ticagrelor.

Strategy for the Treatment of Clopidogrel Low Responsiveness in Diabetes Mellitus and Stent Implantation