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American Journal of Cardiovascular Drugs

, Volume 19, Issue 2, pp 173–183 | Cite as

Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: ATLANTIC-Morphine

  • Frédéric Lapostolle
  • Arnoud W. van’t Hof
  • Christian W. Hamm
  • Olivier Stibbe
  • Patrick Ecollan
  • Jean-Philippe Collet
  • Johanne Silvain
  • Jens Flensted Lassen
  • Wim M. J. M. Heutz
  • Leonardo Bolognese
  • Warren J. Cantor
  • Angel Cequier
  • Mohamed Chettibi
  • Shaun G. Goodman
  • Christopher J. Hammett
  • Kurt Huber
  • Magnus Janzon
  • Béla Merkely
  • Robert F. Storey
  • Jur ten Berg
  • Uwe Zeymer
  • Muriel Licour
  • Anne Tsatsaris
  • Gilles MontalescotEmail author
  • for the ATLANTIC Investigators
Original Research Article
  • 173 Downloads

Abstract

Background

Morphine adversely impacts the action of oral adenosine diphosphate (ADP)-receptor blockers in ST-segment elevation myocardial infarction (STEMI) patients, and is possibly associated with differing patient characteristics. This retrospective analysis investigated whether interaction between morphine use and pre-percutaneous coronary intervention (pre-PCI) ST-segment elevation resolution in STEMI patients in the ATLANTIC study was associated with differences in patient characteristics and management.

Methods

ATLANTIC was an international, multicenter, randomized study of treatment in the acute ambulance/hospital setting where STEMI patients received ticagrelor 180 mg ± morphine. Patient characteristics, cardiovascular history, risk factors, management, and outcomes were recorded.

Results

Opioids (97.6% morphine) were used in 921 out of 1862 patients (49.5%). There were no significant differences in age, sex or cardiovascular history, but more morphine-treated patients had anterior myocardial infarction and left-main disease. Time from chest pain to electrocardiogram and ticagrelor loading was shorter with morphine (both p = 0.01) but not total ischemic time. Morphine-treated patients more frequently received glycoprotein IIb/IIIa inhibitors (p = 0.002), thromboaspiration and stent implantation (both p < 0.001). No significant difference between the two groups was found regarding pre-PCI ≥ 70% ST-segment elevation resolution, death, myocardial infarction, stroke, urgent revascularization and definitive acute stent thrombosis. More morphine-treated patients had an absence of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow (85.8% vs. 79.7%; p = 0.001) and more had TIMI major bleeding (1.1% vs. 0.1%; p = 0.02).

Conclusions

Morphine-treatment was associated with increased GP IIb/IIIa inhibitor use, less pre-PCI TIMI 3 flow, and more bleeding. Judicious morphine use is advised with non-opioid analgesics preferred for non-severe acute pain.

Trial Registration

clinicaltrials.gov identifier: NCT01347580.

Notes

Acknowledgements

G.M. and the ATLANTIC Steering Committee had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The authors would like to thank Richard Cairns, from Worldwide Clinical Trials UK, for statistical analysis. Editorial support was provided by Liz Anfield, Prime, Knutsford, Cheshire, funded by AstraZeneca. All persons named in the acknowledgements section have provided the corresponding author with written permission to be named in the article.

ATLANTIC study investigators

Algeria: Rachid Bougherbal (Algiers), Mohamed Tahar Bouafia (Algiers), Mohamed Chettibi (Algiers), Djamaleddine Nibouche (Medea), Abdelkader Moklati (Tipaza), Ahmed Benalia (Algiers), Omar Kaid (Blida), Messaad Krim (Blida).

Australia: Christopher Hammett (Herston, QLD), Paul Garraby (Woolloogabba, QLD), Rohan Jayasinghe (Southport, QLD), Stephen Rashford (Kedron, QLD).

Austria: Kurt Huber (Vienna), Thomas Neunteufl (Vienna), Helmut Brussee (Graz), Hannes Alber (Innsbruk), Franz Weidinger (Vienna), Michael Brunner (Vienna), Johann Sipoetz (Vienna), Gerhard Prause (Graz), Michael Baubin (Innsbruk), Dieter Sebald (Vienna).

Canada: Warren Cantor (Newmarket, ON),, Ram Vijayaraghavan (Scarborough, ON), Iqbal Bata (Halifax, NS), Andrea Lavoie (Regina, SK).

Denmark: Jens Flensted Lassen (Aarhus), Jan Ravkilde (Aalborg), Lisette Okkels Jensen (Odense C), Alf Møl Christensen (Aarhus), Marianne Toftegaard (Aalborg), Dennis Köhler (Odense C).

France: Gilles Montalescot (Paris), Gregory Ducrocq (Paris), Nicolas Danchin (Paris), Patrick Henry (Paris), Bernard Livarek (Le Chesnay), Romain Berthier (Corbeil Essonnes), Thomas Hovasse (Massy), Philippe Garot (Quincy sous Sénart), Laurent Payot (Montreuil), Hakim Benamer (Aubervilliers), Jean Baptiste Esteve (Montfermeil), Simon Elhadad (Lagny sur Marne), Emmanuel Teiger (Creteil), Jean Louis Bonnet (Marseille), Franck Paganelli (Marseille), Yves Cottin (Dijon), François Schiele (Besançon), Christophe Thuaire (Le Coudray), Guillaume Cayla (Nîmes), Pierre Coste (Pessac), Patrick Ohlmann (Strasbourg), Eric Bonnefoy Cudraz (Bron), Pierre Lantelme (Lyon), Thibault Perret (Lyon), Christophe Tron (Rouen), Axel De Labriolle (Montauban), Edouardo Aptecar (Melun), Olivier Beliard (Neuilly sur Seine), Olivier Varenne (Paris), Rami El Mahmoud (Boulogne Billancourt), Emmanuelle Filippi-Codaccioni (Vannes), Denis Angoulvant (Tours), Patrick Peycher (Tours), Olivier Poitrineau (Chateauroux), Xavier Tabone (Bourges), Patrick Ecollan (Paris), Claire Broche (Paris), Yves Lambert (Chesnay), Nicolas Briole (Corbeil Essonnes), Arielle Beruben (Montfermeil), Nicolas Porcher (Lagny sur Marne), Jean-Pierre Auffray (Marseille), Marc Freysz (Dijon), Franck Depardieu (Besançon), David Poubel (Chartres), Jean-Emmanuel De La Cousaye (Nîmes), Jean-Claude Bartier (Strasbourg), Benoît Jardel (Rouen), Bertrand Boulanger (Vannes), Hervé Labourel (Chambray-les-Tours), Louis-Christophe Soulat (Chateauroux), Frédéric Lapostolle (Bobigny), Véronique Julie (Dreux), Michel Thicoipe (Bordeaux), Olivier Capel (Lyon), Olivier Stibbe (Paris), Pierre Carli (Paris), Karim Tazarourte (Melun), Fabrice Alcouffe (Montauban), David Aboucaya (Clichy), Gaële Aubert (Juvisy sur Orge), Gérald Kierzek (Paris), Séverine Cahun-Giraud (Garches).

Germany: Uwe Zeymer (Ludwigshafen), Christian Hamm (Bad Nauheim), Thomas Dengler (Bad Friedrichshall), Roland Prondzinsky (Mersebourg), Paul Marc Biever (Freiburg), Andreas Schäfer (Hannover), Melchior Seyfarth (Wuppertal), Bernd Lemke (Lüdenscheid), Gerald Werner (Darmstadt), Holger Nef (Gießen), Holger Steiger (Darmstadt), Matthias Leschke (Esslingen), Thomas Münzel (Mainz), Marco Campo Dell Orto (Hessen), Christian Loges (Bad Friedrichshall), Monika Schinke (Merseburg), Frank Koberne (Freiberg), Hans Peter Reiffen (Hannover), Klaus Tiroch (Wuppertal), Dirk Wierich (Lüdenscheidt), Michael Kneussel (Darmstadt), Simon Little (Gießen), Hartmut Sauer (Esslingen), Rita Laufenberg-Feldmann (Mainz).

Hungary: Béla Merkely (Budapest), Imre Ungi (Szeged), Iván Horváth (Pécs), István Édes (Debrecen), István Mártai (Markó).

Italy: Leonardo Bolognese (Arezzo), Sergio Berti (Massa), Francesco Chiarella (Genova), Paolo Calabria (Grosseto), Massimo Fineschi (Siena), Marcello Galvani (Forli), Marco Valgimigli (Cona), Luciano Moretti (Ascoli Piceno), Maurizio Tespili (Seriate), Massimo Mandó (Arezzo), Francesco Bermano (Genova), Robusto Biagioni (Grosseto), Andrea Fabbri (Forli), Adelina Ricciardelli (Ferrara), Maria Romana Petroni (Ascoli Piceno), Umberto Roberto Vatteroni (Massa Carrara), Francesco Palumbo (Siena).

The Netherlands: Frank F. Willems (Arnhem), Amar Al mafragi (Terneuzen), Ton A.A.C.M. Heestermans (Alkmaar), Martijn J. Van Eck (Den Bosch), Wim M.J.M. Heutz (Arnhem), H.H. Meppelder (Goes), Anika Roukema-de Jong (Alkmaar), Harm Van de Pas (Den Bosch).

Spain: Ángel Cequier Fillat (Barcelona), Manel Sabaté Tenas (Barcelona), Josepa Mauri Ferrer (Badalona), Antoni Serra Peñaranda (Barcelona), Joan Ángel Ferrer (Barcelona), Bruno García Del Blanco (Barcelona), Faustino Miranda Guardiola (Barcelona), Juan Miguel Ruiz Nodar (Alicante), Andrés Íñiguez Romo (Vigo), Nicolás Vázquez González (A Coruña), Ramiro Trillo Nouche (A Coruña), Luis Díaz De La Llera (Sevilla), José María Hernández García (Málaga), Fernando Rivero-Crespo (Madrid), Felipe Hernández Hernández (Madrid), José Luis Zamorano Gómez (Madrid), Xavier Jiménez Fárega (Barcelona), Gilberto Alonso Fernández (Barcelona), José Luis Toboso (Badalona), Mercedes Carrasco (Alicante), Victoria Barreiro (A Coruña), José Antonio Iglesias Vázquez (A Coruña), María del Mar Ruiz Montero (Málaga), Fernando Rosell Ortiz (Málaga), Guillermo Garcia Escudero (Málaga), Vicente Sánchez-Brunete Ingelmo (Madrid), Antonio Lara García (Madrid).

Sweden: Magnus Janzon (Linköping),, Jonas Oldgren (Uppsala), Fredrik Calais (Örebro), Robert Kastberg (Gävle), Per-Adolf Bergsten (Linköping), Hans Blomberg (Uppsala),Kristian Thörn (Örebro), Gunnar Skoog (Gävle).

United Kingdom: Robert F. Storey (Sheffield), Azfar Zaman (Newcastle upon Tyne), Robert Gerber (Eastbourne and Hastings), Alisdair Ryding (Norwich), Mark Spence (Belfast), Neil Swanson (Middlesborough), Martin Been (Coventry), Konrad Grosser (Ashford, Kent), Peter Schofield (Cambridge), David Mackin (York), Paul Fell (Newcastle upon Tyne), Tom Quinn (Guildford), Teresa Foster (Cambridge), David McManus (Belfast), Andy Carson (Briery Hill).

Compliance with ethical standards

Funding

This work was supported by AstraZeneca and led by the ACTION Group (Allies in Cardiovascular Trials Initiatives and Organized Networks), www.action-coeur.org.

Conflict of interest

All authors have completed the International Committee of Medical Journal Editors (ICMJE) Form for Disclosure of Potential Conflicts of Interest. Frédéric Lapostolle has received research grants, consultancy fees and honoraria from AstraZeneca, Merck-Serono, Roche, Boehringer-Ingelheim, Bayer, The Medicines Company, Correvio, Daiichi-Sankyo, and Eli-Lilly. Arnoud W. van ‘t Hof has received research grants, consultancy fees and honoraria from AstraZeneca, Medtronic, Daiichi-Sankyo, and Iroko Cardio. Christian W. Hamm has received research grants, consultancy fees, and honoraria from AstraZeneca, Daiichi-Sankyo, Lilly, Sanofi-Aventis, and Boehringer-Ingelheim. Patrick Ecollan has received consultancy fees from AstraZeneca, Abbott Vascular, Eli-Lilly, Sanofi-Aventis, and Biomérieux. Jean-Philippe Collet has received research grants from Bristol-Myers Squibb; consulting fees from Bristol-Myers Squibb, Eli Lilly, and Sanofi-Aventis; and lecture fees from Bristol-Myers Squibb and Sanofi-Aventis. Johanne Silvain has received research grants from Fédération Française de Cardiologie and Société Française de Cardiologie; consultancy fees and honoraria from Amgen, Algorythm AstraZeneca, Bayer, Gilead Science and Sanofi-Aventis; and travel support from Amgen, AstraZeneca, Bayer and Bristol-Myers Squibb. Jens Flensted Lassen has received honoraria from AstraZeneca. Leonardo Bolognese has received consultancy fees and honoraria from AstraZeneca, Daiichi-Sankyo, Eli-Lilly, Menarini Ind Farma, and Abbott. Warren J. Cantor has received honoraria from AstraZeneca. Mohamed Chettibi has received support from AstraZeneca (study investigator). Shaun G. Goodman has received support from AstraZeneca Canada (National [Canada] Coordinator) and consultancy fees and honoraria from AstraZeneca, Eli-Lilly, and Sanofi. Christopher J. Hammett has received research grants from AstraZeneca and consultancy fees and honoraria from AstraZeneca, Eli-Lilly, Bayer Healthcare, Boehringer-Ingelheim, Amgen, and The Medicines Company. Magnus Janzon has received support from AstraZeneca (National Coordinating Investigator) and Pfizer. Robert Storey has received research grants, consultancy fees and honoraria from AstraZeneca; research grants and consultancy fees from PlaqueTec; consultancy fees from Actelion/Idorsia, Avacta, Bayer, Bristol-Myers Squibb, Pfizer, Novartis, and The Medicines Company. Jur ten Berg has received research grants, consultancy fees and honoraria from AstraZeneca. Uwe Zeymer has received research grants from Daiichi-Sankyo, Eli-Lilly, Novartis and Sanofi and consultancy fees and honoraria from AstraZeneca, Bayer Healthcare, The Medicines Company, Daiichi-Sankyo, Eli-Lilly, Novartis, Sanofi, Boehringer-Ingelheim, and Merck-Sharp and Dohme. Gilles Montalescot has received research grants (institution) from ADIR, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Celladon, Daiichi-Sankyo, Eli-Lilly, ICAN, Fédération Française de Cardiologie, Medtronic, Merck-Sharp and Dohme, Pfizer, Sanofi-Aventis, and The Medicines Company and consultancy fees from Amgen, AstraZeneca, Bayer, Berlin Chimie AG, Boehringer-Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Cardiovascular Research Foundation, CME Resources, Daiichi-Sankyo, Eli-Lilly, Europa, Elsevier, Fondazione Anna Maria Sechi per il Cuore, Gilead, Janssen, Lead-Up, Menarini, Merck-Sharp and Dohme, Pfizer, Sanofi-Aventis, The Medicines Company, TIMI Study Group, and WebMD. Muriel Licour and Anne Tsatsaris are employees of AstraZeneca, while Angel Cequier, Béla Merkely, Kurt Huber, Olivier Stibbe, and Wim M.J.M. Heutz have nothing to disclose.

Supplementary material

40256_2018_305_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 kb)

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Frédéric Lapostolle
    • 1
  • Arnoud W. van’t Hof
    • 2
    • 21
  • Christian W. Hamm
    • 3
  • Olivier Stibbe
    • 4
  • Patrick Ecollan
    • 5
  • Jean-Philippe Collet
    • 5
  • Johanne Silvain
    • 5
  • Jens Flensted Lassen
    • 6
  • Wim M. J. M. Heutz
    • 7
  • Leonardo Bolognese
    • 8
  • Warren J. Cantor
    • 9
  • Angel Cequier
    • 10
  • Mohamed Chettibi
    • 11
  • Shaun G. Goodman
    • 12
  • Christopher J. Hammett
    • 13
  • Kurt Huber
    • 14
  • Magnus Janzon
    • 15
  • Béla Merkely
    • 16
  • Robert F. Storey
    • 17
  • Jur ten Berg
    • 18
  • Uwe Zeymer
    • 19
  • Muriel Licour
    • 20
  • Anne Tsatsaris
    • 20
  • Gilles Montalescot
    • 5
    Email author
  • for the ATLANTIC Investigators
  1. 1.SAMU 93 - UF Recherche-Enseignement-Qualité, Université Paris 13, Sorbonne Paris Cité, Inserm U942BobignyFrance
  2. 2.Department of CardiologyIsala ClinicsZwolleThe Netherlands
  3. 3.Department of CardiologyKerckhoff Heart and Thorax CenterBad NauheimGermany
  4. 4.Service Médical d’UrgenceBrigade de Sapeurs-Pompiers de ParisParisFrance
  5. 5.Sorbonne Université, ACTION Study Group, Hôpital Pitié-Salpêtrière (AP-HP)ParisFrance
  6. 6.Department of Cardiology BAarhus University HospitalAarhus NDenmark
  7. 7.Regionale Ambulance Voor ziening Gelderland-MiddenArnhemThe Netherlands
  8. 8.Cardiovascular and Neurological DepartmentAzienda Ospedaliera ArezzoArezzoItaly
  9. 9.Southlake Regional Health CentreUniversity of TorontoNewmarketCanada
  10. 10.Heart Disease Institute, Hospital Universitario de BellvitgeUniversity of Barcelona, L’Hospitalet de LlobregatBarcelonaSpain
  11. 11.Centre Hospito-universitaire Frantz FanonBlidaAlgeria
  12. 12.Division of Cardiology, Canadian Heart Research Centre, St Michael’s HospitalUniversity of TorontoTorontoCanada
  13. 13.Department of CardiologyRoyal Brisbane and Women’s HospitalBrisbaneAustralia
  14. 14.3rd Department of Medicine, Cardiology and Intensive Care Medicine, WilhelminenhospitalSigmund Freud University, Medical SchoolViennaAustria
  15. 15.Department of Cardiology and Department of Medical and Health SciencesLinköping UniversityLinköpingSweden
  16. 16.Heart and Vascular CenterSemmelweis UniversityBudapestHungary
  17. 17.Department of Infection, Immunity and Cardiovascular DiseaseUniversity of SheffieldSheffieldUK
  18. 18.Department of CardiologySt Antonius Hospital NieuwegeinNieuwegeinThe Netherlands
  19. 19.Klinikum Ludwigshafen and Institut für Herzinfarktforschung LudwigshafenLudwigshafenGermany
  20. 20.AstraZenecaRueil MalmaisonFrance
  21. 21.Department of CardiologyMaastricht University Medical CenterMaastrichtThe Netherlands

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