Earlier recovery of platelet function after discontinuation of treatment with ticagrelor compared with clopidogrel in patients with high antiplatelet responses.

BACKGROUND: The rate of recovery of platelet function after discontinuation of P2Y(12) inhibitors depends on the reversibility of the antiplatelet effect and the extent of the on-treatment response. P2Y(12) inhibition increases the bleeding risk in patients requiring surgery. OBJECTIVES: To evaluate recovery of platelet function after discontinuation of ticagrelor vs. clopidogrel in stable coronary artery disease (CAD) patients with high levels of platelet inhibition (HPI) during the ONSET/OFFSET study. METHODS: Patients received aspirin 75-100 mg per day and either ticagrelor 90 mg twice-daily or clopidogrel 75 mg daily for 6 weeks. This subanalysis included patients with HPI after the last dose of maintenance therapy, defined as: inhibition of platelet aggregation (IPA) > 75% 4 h post-dose (ADP 20 μm, final extent); < 120 P2Y(12) reaction units 8 h post-dose (VerifyNow P2Y(12) assay); or platelet reactivity index < 50% 8 h post-dose (VASP-P assay). RESULTS: IPA > 75% was observed in 39 out of 47 ticagrelor-treated and 17 out of 44 clopidogrel-treated patients. The rate of offset of IPA over 4-72 h was greater with ticagrelor (IPA %/hour slope: -1.11 vs. -0.67 for clopidogrel; P < 0.0001). Mean IPA was significantly lower with ticagrelor than clopidogrel between 48 and 168 h post-dose (P < 0.01). Similar findings were observed with the other assays. The average time for IPA to decline from 30% to 10% was 50.8 h with ticagrelor vs. 110.4 h with clopidogrel. CONCLUSIONS: In patients with HPI, recovery of platelet function was more rapid after discontinuation of ticagrelor than clopidogrel leading to significantly greater platelet reactivity by 48 h after the last dose in the ticagrelor group.

Duke Scholars

Author Paul Alfred Gurbel Medicine, Clinical Pharmacology