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 75-100mg per day and either ticagrelor 90mg twice-daily or clopidogrel 75mg daily for 6weeks. This subanalysis included patients with HPI after the last dose of maintenance therapy, defined as: inhibition of platelet aggregation (IPA) >75% 4h post-dose (ADP 20μm, final extent); <120 P2Y ₁₂ reaction units 8h post-dose (VerifyNow P2Y ₁₂ assay); or platelet reactivity index <50% 8h 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 4-72h 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 168h 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 50.8h with ticagrelor vs. 110.4h 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 48h after the last dose in the ticagrelor group.