Clopidogrel Versus Ticagrelor for Antiplatelet Maintenance in Diabetic Patients Treated With Percutaneous Coronary Intervention

September 13, 2016 835 CORRPONDENCE A large proportion of patients with coronary artery disease treated with elective percutaneous coronary intervention have high residual platelet reactivity1 and endothelial dysfunction, which might represent the link to the occurrence of ischemic events.2 This is even more the case for patients with diabetes mellitus, in whom more potent P2Y12 receptor inhibitors have been proposed with promising results in terms of reduced platelet reactivity.3 Nevertheless, whether this enhanced platelet inhibition also might be beneficial to the endothelial function is yet unknown. CLOTILDIA (Clopidogrel High Dose Versus Ticagrelor for Antiplatelet Maintenance in Diabetic Patients)4 was a single-center, prospective, randomized, open label, crossover study, enrolling patients with type 2 diabetes mellitus and stable coronary artery disease treated with percutaneous coronary intervention and drug-eluting stent implantation. Patients were recruited at least 1 month after percutaneous coronary intervention (3.8±2.1 months), while they were still on dual-antiplatelet therapy with aspirin (100 mg/d) and clopidogrel (75 mg/d). At study entry (T0), with the use of a computer-based randomization system, patients were assigned randomly to receive either 90 mg ticagrelor twice daily or clopidogrel 150 mg once daily for 14 days. On day 15 (T1), a crossover was performed to the alternate therapy for an additional 14 days (until T2). At each time point (T0, T1, and T2), all patients underwent ultrasound-based measurement of brachial artery reactivity (including flow-mediated dilation [FMD] and nitroglycerin-mediated dilation [NMD]), and platelet function testing using the VerifyNow P2Y12 assay (Accumetrics). A total of 42 patients were enrolled in this study; 21 were assigned randomly to receive ticagrelor, and 21 were assigned randomly to receive high-dose clopidogrel. Baseline characteristics were similar in the 2 groups. Values of FMD and NMD at the 3 study time points are shown in the Figure. At T0, no significant differences in FMD and NMD were observed between the 2 groups (FMD, 10.0±4.2% versus 9.7±3.4%, P=0.867; NMD, 12.3±3.3% versus 12.3±3.5%, P=0.968). From T0 to T1, both study groups showed a significant increase in FMD (ticagrelor, P<0.001; highdose clopidogrel, P=0.049) and NMD (ticagrelor, P<0.001; high-dose clopidogrel, P=0.034). Yet, at T1 patients who received ticagrelor had significantly higher values of both FMD and NMD values than patients who received high-dose clopidogrel (FMD, 16.0±4.4% versus 12.0±3.6%, P=0.009; NMD, 18.8±3.8% versus 15.1±4.5%, P=0.043). From T1 to T2, although a significant decrease was observed in brachial artery reactivity indexes switching from ticagrelor to high-dose clopidogrel (FMD, P<0.001; NMD, P=0.003), a significant further increase was observed crossing over from high-dose clopidogrel to ticagrelor in both FMD (P<0.001) and NMD (0.009). At T2, patients who received ticagrelor in comparison with patients who received high-dose clopidogrel showed significantly higher values of FMD (17.2±5.4% versus 11.2±4.4%, P<0.001) and NMD (18.6±6.4% versus 13.5±5.9%, P=0.020). At the end of the study drug assignment period, both FMD and NMD values were significantly higher with ticagrelor in comparison with high-dose clopidogrel (FMD, 16.6±4.8% Fabio Mangiacapra, MD, PhD Elena Panaioli, MD Iginio Colaiori, MD Elisabetta Ricottini, MD Angelo Lauria Pantano, MD, PhD Paolo Pozzilli, MD Emanuele Barbato, MD, PhD Germano Di Sciascio, MD