David J Schneider1, Zubin Agarwal2, Naveen Seecheran2, Friederike K Keating2, Prospero Gogo2. 1. Cardiology Unit, and Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington, Vermont. Electronic address: david.schneider@uvm.edu. 2. Cardiology Unit, and Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington, Vermont.
Abstract
OBJECTIVES: This study sought to determine pharmacodynamic effects during transition from intravenous cangrelor to oral ticagrelor and from oral ticagrelor to intravenous cangrelor. BACKGROUND:Cangrelor is an intravenous antagonist of P2Y12 and its use will require transition to and from oral agents. METHODS:Patients (n = 12) with stable coronary artery disease who were taking aspirin 81 mg daily were recruited. On study day 1, they received a bolus plus 2-h infusion of cangrelor plus a 180-mg dose of ticagrelor at either 0.5 h (n = 6) or 1.25 h (n = 6). Pharmacodynamic effects (light transmission platelet aggregation in response to 20 and 5 μmol/l adenosine diphosphate, VerifyNow, P2Y12 assay (Accumetrics, San Diego, California), vasodilator-stimulated phosphoprotein index, and flow cytometry) were assessed during and after the cangrelor infusion. Patients took 90 mg of ticagrelor twice daily for either 6 (n = 6) or 7 (n = 6) doses. On study day 5, pharmacodynamic effects were assessed before and during a bolus plus 2-h infusion of cangrelor. RESULTS: During cangrelor infusion, extensive inhibition of platelet function reflected by limited residual platelet reactivity was apparent. After cangrelor was stopped, the antiplatelet effects of ticagrelor were preserved despite a modest increase in platelet reactivity. CONCLUSIONS:Ticagrelor given before or during infusion of cangrelor did not attenuate the pharmacodynamic effects of cangrelor. The pharmacodynamic effects of ticagrelor were preserved when ticagrelor was given during infusion of cangrelor. Consistent with the reversible binding of ticagrelor, this oral P2Y12 antagonist can be administered before, during, or after treatment with cangrelor.
RCT Entities:
OBJECTIVES: This study sought to determine pharmacodynamic effects during transition from intravenous cangrelor to oral ticagrelor and from oral ticagrelor to intravenous cangrelor. BACKGROUND:Cangrelor is an intravenous antagonist of P2Y12 and its use will require transition to and from oral agents. METHODS:Patients (n = 12) with stable coronary artery disease who were taking aspirin 81 mg daily were recruited. On study day 1, they received a bolus plus 2-h infusion of cangrelor plus a 180-mg dose of ticagrelor at either 0.5 h (n = 6) or 1.25 h (n = 6). Pharmacodynamic effects (light transmission platelet aggregation in response to 20 and 5 μmol/l adenosine diphosphate, VerifyNow, P2Y12 assay (Accumetrics, San Diego, California), vasodilator-stimulated phosphoprotein index, and flow cytometry) were assessed during and after the cangrelor infusion. Patients took 90 mg of ticagrelor twice daily for either 6 (n = 6) or 7 (n = 6) doses. On study day 5, pharmacodynamic effects were assessed before and during a bolus plus 2-h infusion of cangrelor. RESULTS: During cangrelor infusion, extensive inhibition of platelet function reflected by limited residual platelet reactivity was apparent. After cangrelor was stopped, the antiplatelet effects of ticagrelor were preserved despite a modest increase in platelet reactivity. CONCLUSIONS:Ticagrelor given before or during infusion of cangrelor did not attenuate the pharmacodynamic effects of cangrelor. The pharmacodynamic effects of ticagrelor were preserved when ticagrelor was given during infusion of cangrelor. Consistent with the reversible binding of ticagrelor, this oral P2Y12 antagonist can be administered before, during, or after treatment with cangrelor.
Authors: Christopher R Kelly; Ajay J Kirtane; Jennifer Stant; Gregg W Stone; Robert M Minutello; S Chiu Wong; Honeyleen Manuzon; Roxanne Gerow-Smith; Nancy Kelley; LeRoy E Rabbani Journal: Crit Pathw Cardiol Date: 2017-03
Authors: Jennifer A Rymer; Deepak L Bhatt; Dominick J Angiolillo; Miguel Diaz; Kirk N Garratt; Ron Waksman; Laura Edwards; Gudaye Tasissa; Khalid Salahuddin; Hijrah El-Sabae; Carmen Dell'Anna; Linda Davidson-Ray; Jeffrey B Washam; E Magnus Ohman; Tracy Y Wang Journal: J Am Heart Assoc Date: 2022-05-27 Impact factor: 6.106