Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial
IntroductionAmong patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), intravenous fentanyl does not enhance ticagrelor-induced platelet inhibition within 2 h compared to morphine. The impact of the total dose of fentanyl and...
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2024.1324641/full |
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| author | Dorian Garin Sophie Degrauwe Federico Carbone Federico Carbone Yazan Musayeb Nathalie Lauriers Marco Valgimigli Juan F. Iglesias |
| author_facet | Dorian Garin Sophie Degrauwe Federico Carbone Federico Carbone Yazan Musayeb Nathalie Lauriers Marco Valgimigli Juan F. Iglesias |
| author_sort | Dorian Garin |
| collection | DOAJ |
| description | IntroductionAmong patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), intravenous fentanyl does not enhance ticagrelor-induced platelet inhibition within 2 h compared to morphine. The impact of the total dose of fentanyl and morphine received on ticagrelor pharmacodynamic and pharmacokinetic responses in patients with STEMI remains however undetermined.Materials and methodsWe performed a post-hoc subanalysis of the prospective, open-label, single-center, randomized PERSEUS trial (NCT02531165) that compared treatment with intravenous fentanyl vs. morphine among symptomatic patients with STEMI treated with primary PCI after ticagrelor pretreatment. Patients from the same population as PERSEUS were further stratified according to the total dose of intravenous opioids received. The primary outcome was platelet reactivity using P2Y12 reaction units (PRU) at 2 h following administration of a loading dose (LD) of ticagrelor. Secondary outcomes were platelet reactivity and peak plasma levels of ticagrelor and AR-C124910XX, its active metabolite, at up to 12 h after ticagrelor LD administration. Generalized linear models for repeated measures were built to determine the relationship between raw and weight-weighted doses of fentanyl and morphine.Results38 patients with STEMI were included between December 18, 2015, and June 22, 2017. Baseline clinical and procedural characteristics were similar between low- and high-dose opioid subgroups. At 2 h, there was a significant correlation between PRU and both raw [regression coefficient (B), 0.51; 95% confidence interval (CI), 0.02–0.99; p = 0.043] and weight-weighted (B, 0.54; 95% CI, 0.49–0.59; p < 0.001) doses of fentanyl, but not morphine. Median PRU at 2 h was significantly lower in patients receiving low, as compared to high, doses of fentanyl [147; interquartile range (IQR), 63–202; vs. 255; IQR, 183–274; p = 0.028], whereas no significant difference was found in those receiving morphine (217; IQR, 165–266; vs. 237; IQR, 165–269; p = 0.09). At 2 h, weight-weighted doses of fentanyl and morphine were significantly correlated to plasma levels of ticagrelor and AR-C124910XX.ConclusionIn symptomatic patients with STEMI who underwent primary PCI after ticagrelor pretreatment and who received intravenous opioids, we found a dose-dependent relationship between the administration of intravenous fentanyl, but not morphine, and ticagrelor-induced platelet inhibition. |
| first_indexed | 2024-04-24T15:29:49Z |
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| id | doaj.art-555b3309aa904145be8d92f6e9de3c06 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-24T15:29:49Z |
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| spelling | doaj.art-555b3309aa904145be8d92f6e9de3c062024-04-02T04:45:38ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2024-04-011110.3389/fcvm.2024.13246411324641Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trialDorian Garin0Sophie Degrauwe1Federico Carbone2Federico Carbone3Yazan Musayeb4Nathalie Lauriers5Marco Valgimigli6Juan F. Iglesias7Department of Cardiology, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Cardiology, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, ItalyIRCCS Ospedale Policlinico San Martino Genoa, Italian Cardiovascular Network, Genoa, ItalyDepartment of Cardiology, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Cardiology, Lausanne University Hospital, Lausanne, SwitzerlandIstituto Cardiocentro Ticino, Ente Ospedaliero Cantonale, Lugano, SwitzerlandDepartment of Cardiology, Geneva University Hospitals, Geneva, SwitzerlandIntroductionAmong patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), intravenous fentanyl does not enhance ticagrelor-induced platelet inhibition within 2 h compared to morphine. The impact of the total dose of fentanyl and morphine received on ticagrelor pharmacodynamic and pharmacokinetic responses in patients with STEMI remains however undetermined.Materials and methodsWe performed a post-hoc subanalysis of the prospective, open-label, single-center, randomized PERSEUS trial (NCT02531165) that compared treatment with intravenous fentanyl vs. morphine among symptomatic patients with STEMI treated with primary PCI after ticagrelor pretreatment. Patients from the same population as PERSEUS were further stratified according to the total dose of intravenous opioids received. The primary outcome was platelet reactivity using P2Y12 reaction units (PRU) at 2 h following administration of a loading dose (LD) of ticagrelor. Secondary outcomes were platelet reactivity and peak plasma levels of ticagrelor and AR-C124910XX, its active metabolite, at up to 12 h after ticagrelor LD administration. Generalized linear models for repeated measures were built to determine the relationship between raw and weight-weighted doses of fentanyl and morphine.Results38 patients with STEMI were included between December 18, 2015, and June 22, 2017. Baseline clinical and procedural characteristics were similar between low- and high-dose opioid subgroups. At 2 h, there was a significant correlation between PRU and both raw [regression coefficient (B), 0.51; 95% confidence interval (CI), 0.02–0.99; p = 0.043] and weight-weighted (B, 0.54; 95% CI, 0.49–0.59; p < 0.001) doses of fentanyl, but not morphine. Median PRU at 2 h was significantly lower in patients receiving low, as compared to high, doses of fentanyl [147; interquartile range (IQR), 63–202; vs. 255; IQR, 183–274; p = 0.028], whereas no significant difference was found in those receiving morphine (217; IQR, 165–266; vs. 237; IQR, 165–269; p = 0.09). At 2 h, weight-weighted doses of fentanyl and morphine were significantly correlated to plasma levels of ticagrelor and AR-C124910XX.ConclusionIn symptomatic patients with STEMI who underwent primary PCI after ticagrelor pretreatment and who received intravenous opioids, we found a dose-dependent relationship between the administration of intravenous fentanyl, but not morphine, and ticagrelor-induced platelet inhibition.https://www.frontiersin.org/articles/10.3389/fcvm.2024.1324641/fullfentanyldosepharmacodynamicspharmacokineticsST-segment elevation myocardial infarctionticagrelor |
| spellingShingle | Dorian Garin Sophie Degrauwe Federico Carbone Federico Carbone Yazan Musayeb Nathalie Lauriers Marco Valgimigli Juan F. Iglesias Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial Frontiers in Cardiovascular Medicine fentanyl dose pharmacodynamics pharmacokinetics ST-segment elevation myocardial infarction ticagrelor |
| title | Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial |
| title_full | Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial |
| title_fullStr | Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial |
| title_full_unstemmed | Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial |
| title_short | Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial |
| title_sort | differential impact of fentanyl and morphine doses on ticagrelor induced platelet inhibition in st segment elevation myocardial infarction a subgroup analysis from the perseus randomized trial |
| topic | fentanyl dose pharmacodynamics pharmacokinetics ST-segment elevation myocardial infarction ticagrelor |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2024.1324641/full |
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