What drives thrombogenesis despite antiplatelet therapy in diabetes mellitus?

Corresponding author: Robert F Storey, Department of Cardiovascular Science, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK. Email: r.f.storey@sheffield.ac.uk fibrillation will provide new information about the impact of thrombin inhibition on ischaemic events in diabetic compared with non-diabetic patients. Ongoing studies of the alternative strategy of targeting the principal platelet thrombin receptor, PAR-1, rather than thrombin itself will also reveal the potential of adding a further platelet inhibitor to aspirin and a P2Y 12 inhibitor in high-risk patients. This strategy has the advantage of more limited effects on haemostasis compared with anticoagulant therapies yet potentially synergistic antithrombotic effects and so the clinical trial results are eagerly awaited to determine whether it is possible to reduce rates of myocardial infarction and death without significantly compromising haemostasis. It is clear that the mechanisms by which diabetes mellitus drives increased propensity to thrombogenesis will continue to be unravelled in future work and our evolving scientific understanding will underpin new therapeutic strategies that reduce morbidity and mortality due to atherothrombosis in patients with diabetes mellitus.

[1]  MadhuChintala,et al.  SCH 602539, a Protease-Activated Receptor-1 Antagonist, Inhibits Thrombosis Alone and in Combination With Cangrelor in a Folts Model of Arterial Thrombosis in Cynomolgus Monkeys , 2010 .

[2]  D. Angiolillo,et al.  Review article: Platelet abnormalities in diabetes mellitus , 2010, Diabetes & vascular disease research.

[3]  Á. Cequier,et al.  Review article: Antithrombotic therapy in patients with diabetes mellitus and coronary artery disease , 2010, Diabetes & vascular disease research.

[4]  S. Stevens,et al.  Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial , 2010, European heart journal.

[5]  R. Investigators Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study. , 2010, American heart journal.

[6]  C. Held,et al.  The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA*CER) trial: study design and rationale. , 2009, American heart journal.

[7]  Deepak L. Bhatt,et al.  Apixaban, an Oral, Direct, Selective Factor Xa Inhibitor, in Combination With Antiplatelet Therapy After Acute Coronary Syndrome: Results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) Trial , 2009, Circulation.

[8]  Insung Chung,et al.  Faculty Opinions recommendation of Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction , 2009 .

[9]  R. Storey,et al.  Aspirin resistance and diabetes mellitus , 2008, Diabetologia.

[10]  Hidero Suzuki,et al.  Coagulation and fibrinolysis in diabetes mellitus , 1986 .

[11]  M. Chintala,et al.  Basic and translational research on proteinase-activated receptors: antagonism of the proteinase-activated receptor 1 for thrombin, a novel approach to antiplatelet therapy for atherothrombotic disease. , 2008, Journal of pharmacological sciences.