Choices for Potent Platelet Inhibition in Patients With Diabetes Mellitus
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Article, see p 780
Diabetes mellitus provides challenges to clinicians seeking to optimize the efficacy of pharmacological therapies for the management and prevention of atherothrombotic events. On the one hand, it drives the progression of atherosclerosis, leading to the highly thrombogenic rupture and erosion of plaques, at the same time as increasing the thrombogenicity of blood through modulation of platelet reactivity, enhancement of plasma coagulability, and impairment of endogenous fibrinolysis.1 On the other hand, it is associated with reduced pharmacodynamic action of traditional oral antiplatelet therapies (aspirin and clopidogrel) through increased platelet turnover and, in the case of clopidogrel, impairment of hepatic active metabolite generation, thus rendering these therapies less effective despite the clinical imperative for more effective treatment.1 It was therefore inevitable that more effective treatments should be developed for patients who have diabetes mellitus, and others at high risk of atherothrombotic events, as well. This concept is well illustrated in the work of Franchi and colleagues2 who, in this issue of Circulation, have compared the pharmacodynamic properties of prasugrel and ticagrelor in patients with diabetes mellitus.
A key component of the rationale for comparing the effects of prasugrel and ticagrelor in patients who have diabetes mellitus is the different patterns of benefits seen in the diabetes subgroups in the pivotal phase 3 studies of these drugs in comparison with clopidogrel.3,4 With prasugrel, a particularly marked early benefit in reduced thrombotic events was seen in the diabetes subgroup, whereas, with ticagrelor, there was a more progressive accrual of benefit over 1 year, including progressive reduction in mortality. However, differences in study design can explain much of the difference in the patterns of early benefit: the clopidogrel regimen was substantially different between the 2 studies, with prasugrel being compared with a 300-mg loading …