PDF icon PDF herunterladen
Open Access
CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2698-3958
Cellular Haemostasis and Platelets

Methoxyflurane Instead of Morphine in Acute Coronary Syndrome Patients: Results of the Randomized Controlled METHANE-SIRIO 4 Study

Piotr Niezgoda  ‡   ‡
1   Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Przemysław Podhajski‡   ‡
1   Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Michał Kasprzak
1   Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Malwina Barańska
1   Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Oscar Rakotoarison
2   Institute for Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
,
Bożena Karolko
2   Institute for Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
,
Łukasz Pietrzykowski
3   Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Piotr Michalski
3   Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Agata Kosobucka
3   Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Adam Sikora
4   The Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
5   Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University, Szczecin, Poland
,
Joanna Chałupka
4   The Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
5   Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University, Szczecin, Poland
,
Michał Marszałł
4   The Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Wiktor Kuliczkowski 
2   Institute for Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
,
Aldona Kubica
3   Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Jacek Kubica
1   Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
› Institutsangaben
Funding Information This work was supported entirely by Nicolaus Copernicus University in Toruń, grant no. IND.WL.1.202.
› Weitere Informationen
  Lizenzen und Reprints


Preview

Abstract

Aim

Morphine is known to negatively influence the pharmacokinetics (PK) and the antiplatelet effect of oral P2Y12 receptor inhibitors administered due to an acute coronary syndrome. Worldwide studies of the potential approaches to overcome the undesired morphine effect have been only partially successful. The aim of the METHANE-SIRIO 4 study was to evaluate the PK and pharmacodynamics of ticagrelor and its active metabolite in unstable angina (UA) patients treated with morphine or methoxyflurane.

Methods and Results

Consecutive patients diagnosed with UA, randomized into the study arms, underwent the assessment of platelet reactivity using the Multiplate analyzer at nine predefined study time points. Serum concentrations of ticagrelor and its active metabolite, AR-C124910XX, were measured for each study participant. Median platelet reactivity was significantly lower in patients who received ticagrelor and methoxyflurane versus ticagrelor alone at 30 minutes postticagrelor loading dose. A trend toward lower reactivity was observed at 45 and 240 minutes. Significant differences in median serum concentrations of ticagrelor and its active metabolite were most pronounced between patients treated with ticagrelor and methoxyflurane versus ticagrelor and morphine.

Conclusion

Co-administration of methoxyflurane in acute coronary syndrome patients allows for the avoidance of negative effects of morphine and has the additional effect of inhibiting platelet reactivity. Further randomized studies would be recommended to support these findings.

Keywords

acute coronary syndrome - unstable angina - methoxyflurane - morphine - platelet reactivity

Data Availability Statement

The data underlying this article will be shared on reasonable request to the corresponding author.


‡ These authors contributed equally to this article.




Publikationsverlauf

Eingereicht: 11. März 2025

Angenommen: 26. August 2025

Artikel online veröffentlicht:
18. September 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany