open access

Vol 29, No 4 (2022)
Original Article
Submitted: 2022-02-08
Accepted: 2022-05-01
Published online: 2022-05-30
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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

Juan F. Iglesias1, Marco Valgimigli2, Federico Carbone34, Nathalie Lauriers5, Pier-Giorgio Masci5, Sophie Degrauwe1
DOI: 10.5603/CJ.a2022.0049
·
Pubmed: 35762079
·
Cardiol J 2022;29(4):591-600.
Affiliations
  1. Department of Cardiology, Geneva University Hospitals, Geneva, Switzerland
  2. Department of Cardiology, Cardiocentro Ticino, Lugano, Switzerland, Switzerland
  3. First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Italy
  4. IRCCS Ospedale Policlinico San Martino Genoa, Italian Cardiovascular Network, Genoa, Italy
  5. Department of Cardiology, Lausanne University Hospital, Lausanne, Switzerland

open access

Vol 29, No 4 (2022)
Original articles — Clinical cardiology
Submitted: 2022-02-08
Accepted: 2022-05-01
Published online: 2022-05-30

Abstract

Background: 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). Methods: 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). Results: 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. Conclusions: 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.

Abstract

Background: 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). Methods: 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). Results: 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. Conclusions: 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.

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Keywords

fentanyl, pharmacodynamics, pharmacokinetics, ST-segment elevation myocardial infarction, ticagrelor

About this article
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

Issue

Vol 29, No 4 (2022)

Article type

Original Article

Pages

591-600

Published online

2022-05-30

Page views

2433

Article views/downloads

573

DOI

10.5603/CJ.a2022.0049

Pubmed

35762079

Bibliographic record

Cardiol J 2022;29(4):591-600.

Keywords

fentanyl
pharmacodynamics
pharmacokinetics
ST-segment elevation myocardial infarction
ticagrelor

Authors

Juan F. Iglesias
Marco Valgimigli
Federico Carbone
Nathalie Lauriers
Pier-Giorgio Masci
Sophie Degrauwe

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