Comparative effects of fentanyl versus morphine on platelet inhibition induced by ticagrelor in patients with ST-segment elevation myocardial infarction: Full results of the PERSEUS randomized trial.

Details

Serval ID
serval:BIB_EA3BAC8B3284
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Comparative effects of fentanyl versus morphine on platelet inhibition induced by ticagrelor in patients with ST-segment elevation myocardial infarction: Full results of the PERSEUS randomized trial.
Journal
Cardiology journal
Author(s)
Iglesias J.F., Valgimigli M., Carbone F., Lauriers N., Masci P.G., Degrauwe S.
ISSN
1898-018X (Electronic)
ISSN-L
1898-018X
Publication state
Published
Issued date
2022
Peer-reviewed
Oui
Volume
29
Number
4
Pages
591-600
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial
Publication Status: ppublish
Abstract
Morphine reduces absorption and delays action onset of potent oral P2Y₁₂ receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the differential effects of fentanyl compared to morphine on the pharmacodynamics and pharmacokinetics of ticagrelor in STEMI patients undergoing primary percutaneous coronary intervention (PCI).
PERSEUS (NCT02531165) was a prospective, single-center, open-label, randomized controlled study. Patients with STEMI who required analgesia were randomly assigned in a 1:1 ratio to treatment with intravenous fentanyl or morphine after ticagrelor loading dose (LD) administration. The primary endpoint was platelet reactivity at 2 hours after ticagrelor LD assessed by P2Y₁₂ reaction units (PRU).
The study was prematurely stopped in June 2017 after enrolment of 38 out of 56 planned patients. PRU at 2 hours following ticagrelor LD was 173.3 ± 89.7 in the fentanyl group and 210.3 ± 76.4 in the morphine group (p = 0.179). At 4 hours, PRU was significantly lower among patients treated with fentanyl as compared to those treated with morphine (90.1 ± 97.4 vs. 168.0 ± 72.2; p = 0.011). Maximal plasma concentrations of ticagrelor and its active metabolite AR-C124910XX tended to be delayed and numerically lower among patients treated with morphine compared to fentanyl. Total exposures to ticagrelor and AR-C124910XX within 6 hours after ticagrelor LD were numerically greater among patients treated with fentanyl compared to those treated with morphine.
In patients with STEMI undergoing primary PCI, fentanyl did not improve platelet inhibition at 2 hours after ticagrelor pre-treatment compared with morphine. Fentanyl may, however, accelerate ticagrelor absorption and increase platelet inhibition at 4 hours compared to morphine.
Keywords
Fentanyl/adverse effects, Humans, Morphine, Percutaneous Coronary Intervention/adverse effects, Platelet Aggregation Inhibitors, Platelet Function Tests, Prospective Studies, Purinergic P2Y Receptor Antagonists, ST Elevation Myocardial Infarction/diagnosis, ST Elevation Myocardial Infarction/drug therapy, Ticagrelor/adverse effects, Treatment Outcome, ST-segment elevation myocardial infarction, fentanyl, pharmacodynamics, pharmacokinetics, ticagrelor
Pubmed
Web of science
Open Access
Yes
Create date
04/07/2022 12:31
Last modification date
21/11/2023 8:09
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