Interaction of diabetes with antithrombotic agents Symposium 

Professor Verheugt said that, on balance, platelet response to aspirin appears reduced in diabetes, although post-hoc analyses suggest similar aspirin benefits for diabetics and non-diabetics in preventing recurrent ischemia. The presence of diabetes by itself does not change the indication for aspirin therapy, he said. Ongoing prospective studies will better define aspirin’s role in diabetes.

Professor Bhatt said clopidogrel was superior to aspirin in preventing adverse events among both diabetics and non-diabetics with recent ischemia (CAPRIE). He suggested clopidogrel plus aspirin may be superior to aspirin alone for long-term secondary prevention in both diabetics and non-diabetics, but not for primary prevention in men and women with multiple risk factors (CHARISMA). Diabetics show greater ex vivo platelet reactivity at baseline, he said, and lesser platelet inhibition after clopidogrel, compared to non-diabetic patients. Current randomised studies that are testing higher doses of clopidogrel and the newer ADP-P2Y12 receptor antagonists (prasugrel, AZD6140 and cangrelor) should provide further information relevant to diabetes.

Professor Huber said that most data on glycoprotein IIb/IIIa receptor inhibitors in diabetics come from post-hoc analyses, before the widespread use of clopidogrel. These inhibitors seem to offer clinical benefit in diabetics with unstable coronary syndromes, when treated conservatively and, even more so, when undergoing percutaneous coronary interventions. In the randomised ISAR-SWEET trial of 701 diabetics, however, abciximab on top of clopidogrel, compared to placebo, did not significantly reduce the risk of death or myocardial infarction one year after elective percutaneous revascularization, he noted, although restenosis rates were lower. Prospective data are few, and more information is needed on the interaction with clopidogrel, he added.

Professor Arnesen presented an insightful post-hoc analysis of 3 large randomised trials: WARIS, ASPECT, and WARIS II. He consistently showed that, with diabetes, oral anticoagulants lacked effectiveness in preventing major adverse events after myocardial infarction. In this setting, he said, antiplatelet agents might be preferred. Thrombotic mechanisms may differ in diabetes, he observed, through special involvement of advanced glycation end-products, nitric oxide, the thrombin-thrombomodulin-protein C/S pathway, or vitamin K-independent thrombin generation.