Abstract 5901: The Effect of Ticagrelor in Stable Coronary Artery Disease Patients Nonresponsive to Clopidogrel: The RESPOND Study
Background: Ticagrelor (T), the first reversibly binding oral P2Y12 receptor antagonist, has been evaluated in patients with ACS in the phase III PLATO trial. The effect of T in patients who are nonresponsive to clopidogrel (C) is unknown.
Methods: Patients with stable coronary artery disease on aspirin therapy (75 – 100 mg qd) were enrolled and administered a 300 mg C load (n = 98). C nonresponders (NR) were defined as those exhibiting ≤10% absolute change from baseline in maximal platelet aggregation (PA) determined by conventional light transmittance aggregometry (LTA) (20 μM ADP) at 6 – 8 h following the load. In a 2-way crossover design, NR (n=41) and C responders (R) (n=57) were randomized to receive either C 600 mg load/75 mg qd for 14 days or T 180 mg load/90 mg bid for 14 days during Period I. Patients then proceeded to Period II with no washout. In Period II, NR were switched to the other treatment; half of the R continued their assigned treatments received in Period I, and the other half of the R were switched to the other treatment. Platelet reactivity was assessed by LTA and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) on Days 1 and 14 of each Period. Differences between T and C were analyzed by ANCOVA.
Results: PA was lower in NR treated with T as compared with C (p<0.05). Following 14 days of C treatment in NR in Period I, switching to T in Period II resulted in a ≤10%, >10-<30% and ≥30% decrease in PA from the baseline in 0%, 19%, and 81%, respectively at 4 hours post-dosing on day 14. Mean platelet aggregation on Day 14 of Period II (4 h post-dose), decreased from 47% to 21% in patients switched from C for T and increased from 20% to 42% in patients switched from T to C (p< 0.05 for both). Consistently higher inhibition of platelet aggregation (IPA) on both Days 1 and 14 for T was present in both R and NR (p<0.05). The mean IPA 4 – 8 h following the loading dose of T was 80 –96% in R and 74 –90% in NR with or without prior C treatment. VASP-P data were concordant with aggregometry.
Conclusions: Clopidogrel NR and R exhibit superior platelet inhibition during therapy with ticagrelor. Ticagrelor therapy effectively overcomes nonresponsiveness to clopidogrel.