Abstract 5900: Differential Effect of Ticagrelor versus Clopidogrel on the Prevalence of High On-Treatment Platelet Reactivity: Results From the Onset-offset Study
Background: High on-treatment platelet reactivity to ADP (HPR) has been strongly linked to adverse event occurrence following coronary artery stenting in patients treated with aspirin and clopidogrel (C). The prevalence of HPR following treatment with ticagrelor (T), the first reversibly binding oral P2Y12 receptor antagonist, was compared with C in patients with stable coronary artery disease (CAD) in the ONSET-OFFSET study.
Methods: In a multicenter, randomized, double-blind, parallel-group study, 123 patients with stable CAD receiving aspirin (75–100 mg) were randomized to doses of T (180 mg load, 90 mg bid maintenance [n=57]), C (600 mg load, 75 mg qd maintenance [n=54]) or placebo (n=12) for 6 weeks. Light transmittance aggregometry (LTA) with ADP (20 uM), VerifyNow P2Y12 (VN), and vasodilator-stimulated phosphoprotein phosphorylation index (VASP-P) assays were performed predose; 2, 8, and 24 h after first dose; and after 6 weeks of maintenance treatment. HPR was defined by previously published cutpoints associated with risk of post-PCI ischemic events: LTA (20 uM ADP):≥59%; VN:>235 PRU; VASP-P>50%. Proportion differences for T versus C were analyzed by Chi-square test for each timepoint. Correlations between each different method were analyzed by Pearson method.
Results: T was associated with significantly lower prevalence of HPR compared with C at all time points post dose, as assessed by LTA, VN, and VASP-P (Table⇓). Placebo prevalences of HPR were consistently high (67–100%). Good correlations presented among LTA, VN, and VASP-P values (R 0.78 for LTA vs VN, 0.70 for LTA vs VASP, 0.83 for VN vs VASP, all p<0.0001).
Conclusions: Ticagrelor therapy is consistently associated with a very low prevalence of HPR compared with clopidogrel, as determined by multiple established methods used to measure platelet reactivity, which has been associated with ischemic risk. This provides mechanistic explanation for the clinical benefits of ticagrelor in ACS patients.