Abstract 19153: Morphine Delays and Attenuates Ticagrelor Exposure and Action in Patients With Myocardial Infarction: The Randomized, Double-blind, Placebo-controlled Impression Trial
Introduction: The currently available data from observational studies and a randomized trial on clopidogrel conducted in healthy volunteers suggest existence of drug-drug interactions between morphine and oral P2Y12 inhibitors, when administered together.
Hypothesis: We aimed to test the hypothesis that morfine administered intravenously excerts the negative impact on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with myocardial infarction.
Methods: In a single center, randomized, double-blind trial, participants were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry, while ticagrelor antiplatelet effect was measured with up to 3 different platelet function tests: vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, multiple electrode aggregometry and VerifyNow P2Y12.
Results: The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine administration lowered the total exposure to ticagrelor and its active metabolite by 35.6% (AUC(0-12): 6307 vs. 9791 ng·h/mL; p=0.003) and 37.1% (AUC(0-12): 1503 vs. 2388 ng·h/mL; p=0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; p=0.002) and AR-C124910XX (6 vs. 4 h; p=0.03) in morphine-treated patients. Multiple regression analysis showed that lower AUC(0-12) values for ticagrelor were associated with morphine administration (p=0.003) and the presence of ST-segment elevation myocardial infarction (p=0.010). All three methods of platelet reactivity assessment consistently showed a stronger antiplatelet effect of ticagrelor in the placebo group as reflected by a higher prevalence of high platelet reactivity in patients receiving morphine.
Conclusions: Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction.
Author Disclosures: J. Kubica: Honoraria; Modest; consulting fee from AstraZeneca. P. Adamski: None. M. Ostrowska: None. J. Sikora: None. J.M. Kubica: None. W. Sroka: None. K. Stankowska: None. K. Buszko: None. E.P. Navarese: None. B. Jilma: None. J.M. Siller-Matula: None. D. Rosc: None. M. Marszall: None. M. Kozinski: None.
- © 2015 by American Heart Association, Inc.