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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

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Titel: 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
Autoren: Iglesias J. F., Valgimigli M., Carbone F., Lauriers N., Masci P. -G., Degrauwe S.
Quelle: Cardiol J
Cardiology journal, vol. 29, no. 4, pp. 591-600
Verlagsinformationen: VM Media SP. zo.o VM Group SK, 2022.
Publikationsjahr: 2022
Schlagwörter: Ticagrelor, Morphine, Platelet Function Tests, fentanyl, pharmacodynamics, pharmacokinetics, ST-segment elevation myocardial infarction, ticagrelor, Clinical Cardiology, 3. Good health, Fentanyl, 03 medical and health sciences, Percutaneous Coronary Intervention, Treatment Outcome, 0302 clinical medicine, Purinergic P2Y Receptor Antagonists, Humans, ST Elevation Myocardial Infarction, Fentanyl/adverse effects, Percutaneous Coronary Intervention/adverse effects, Platelet Aggregation Inhibitors, Prospective Studies, ST Elevation Myocardial Infarction/diagnosis, ST Elevation Myocardial Infarction/drug therapy, Ticagrelor/adverse effects
Beschreibung: 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.
Publikationsart: Article
Other literature type
Dateibeschreibung: application/pdf
ISSN: 1898-018X
1897-5593
DOI: 10.5603/cj.a2022.0049
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/35762079
https://serval.unil.ch/resource/serval:BIB_EA3BAC8B3284.P001/REF.pdf
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http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_EA3BAC8B32848
https://hdl.handle.net/11567/1162862
https://doi.org/10.5603/CJ.a2022.0049
Rights: CC BY NC ND
URL: http://creativecommons.org/licenses/by-nc-nd/4.0/This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially
Dokumentencode: edsair.doi.dedup.....1b78ec283e12edcf10b7cdbe61b86ef8
Datenbank: OpenAIRE
Beschreibung
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.
ISSN:1898018X
18975593
DOI:10.5603/cj.a2022.0049