Background: Multiple studies have shown that there is wide variability in the response to clopidogrel, and that patients with low response (high on treatment platelet reactivity - HTPR) are at increased risk of adverse cardiac events. Ticagrelor has been shown to have superior antiplatelet effects to those of clopidogrel, which have translated to reduction of clinical ischemic events in the PLATO study. However, the antiplatelet efficacy of ticagrelor in patients with diabetes and HTPR during clopidogrel treatment has not been tested.
Methods: We recruited patients with diabetes and stable or unstable angina (no Troponin elevation), planned to undergo coronary angiography with possible percutaneous coronary intervention (PCI). Patients were included in the study if they received chronic clopidogrel treatment or were preloaded with clopidogrel 300 mg at least 24 hours before angiography. Platelet reactivity was tested using the VerifyNow P2Y12 assay, and HTPR was defined as a PRU ≥ 208. Patients with HTPR were randomized to receive before the coronary angiography either additional clopidogrel 300 mg or ticagrelor 180 mg, with subsequent respective treatment following PCI. Additional VerifyNow testing was performed 24 hours after the PCI.
Results: We enrolled 168 diabetic patients (mean age 64.6±9.9 years, 70.6% men) during the study period. A total of 92 (54.8%) patients responded well to clopidogrel (mean PRU 128.6±66.5). Seventy-six patients (45.2%) had HTPR (mean PRU 271.2±45.5), and were randomly assigned to clopidogrel or ticagrelor treatment. Among these patients only 46 patients (61.3%) underwent PCI (26 patients treated with ticagrelor and 19 patients with clopidogrel). Baseline and post-treatment PRU among the two groups are presented in the figure. None of the patients in the ticagrelor group had HTPR, while 10 patients (52.6%) in the clopidogrel group had persistent HTPR.
