Sergio Leonardi1, Enrico Frigoli2, Martina Rothenbühler3, Eliano Navarese4, Paolo Calabró5, Paolo Bellotti6, Carlo Briguori7, Marco Ferlini1, Bernardo Cortese8, Alessandro Lupi9, Salvatore Lerna10, Dennis Zavallonito-Parenti11, Giovanni Esposito12, Simone Tresoldi13, Antonio Zingarelli14, Stefano Rigattieri15, Cataldo Palmieri16, Armando Liso17, Fabio Abate18, Marco Zimarino19, Marco Comeglio20, Gabriele Gabrielli21, Alaide Chieffo22, Salvatore Brugaletta23, Ciro Mauro24, Nicolas M Van Mieghem25, Dik Heg3, Peter Jüni26, Stephan Windecker27, Marco Valgimigli28. 1. Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 2. EUSTRATEGY Association, Forli', Italy. 3. CTU Bern, University of Bern, Switzerland Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland. 4. Policlinico Multimedica IRCSS, University of Milan, Milan, Italy. 5. Division of Cardiology, Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy. 6. Department of Cardiology, ASL3 Ospedale Villa Scassi, Genoa, Italy. 7. Clinica Mediterranea, Napoli, Italy. 8. Ospedale Fatebene Fratelli, Milano, Italy. 9. University Hospital Maggiore della Carità, Novara, Italy. 10. Ospedale Sirai-Carbonia, Carbonia, Italy. 11. Humanitas Research Hospital, IRCCS, Rozzano, Italy. 12. Division of Cardiology-Department of Advanced Biomedical Sciences, Federico II University of Naples. 13. A O Ospedale di Desio, Lombardia, Italy. 14. IRCCS San Martino-IST, Genoa, Italy. 15. Interventional Cardiology Sandro Pertini Hospital Rome, Italy. 16. Ospedale Pasquinucci, Massa, Italy. 17. Citta' di Lecce Hospital, Lecce, Italy. 18. Ospedale Giovanni Paolo II, Sciacca, Italy. 19. Università degli Studi G d'Annunzio Chieti e Pescara, Chieti, Italy. 20. Ospedale San Jacopo, Pistoia, Italy. 21. Azienda Ospedali Riuniti-Presidio GM Lancisi, Ancona, Italy. 22. Ospedale San Raffaele IRCCS, Milano, Italy. 23. Hospital Clinic, Cardiovascular Institute, IDIBAPS, Barcelona, Spain. 24. AORN Cardarelli, Napoli, Italy. 25. Erasmus MC, Rotterdam, Netherlands. 26. Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, and Department of Medicine, University of Toronto, Canada. 27. Swiss Cardiovascular Centre Bern, Bern University Hospital, CH-3010 Bern, Switzerland. 28. Swiss Cardiovascular Centre Bern, Bern University Hospital, CH-3010 Bern, Switzerland marco.valgimigli@insel.ch.
Abstract
OBJECTIVE: To test the optimal antithrombotic regimen in patients with acute coronary syndrome. DESIGN: Randomised controlled trial. SETTING:Patients with acute coronary syndrome with and without ST segment elevation in 78 centres in Italy, the Netherlands, Spain, and Sweden. PARTICIPANTS: 7213 patients with acute coronary syndrome and planned percutaneous coronary intervention: 4010 with ST segment elevation and 3203 without ST segment elevation. The primary study results in the overall population have been reported previously. INTERVENTIONS: Patients were randomly assigned, in an open label fashion, to one of two regimens: bivalirudin with glycoprotein IIb/IIIa inhibitors restricted to procedural complications or heparin with or without glycoprotein IIb/IIIa inhibitors. MAIN OUTCOME MEASURES: Primary endpoints were the occurrence of major adverse cardiovascular events, defined as death, myocardial infarction or stroke; and net adverse clinical events, defined as major bleeding or major adverse cardiovascular events, both assessed at 30 days. Analyses were performed by the principle of intention to treat. RESULTS: Use of a glycoprotein IIb/IIIa inhibitor in patients assigned to heparin was planned at baseline in 30.7% of patients with ST segment elevation, in 10.9% without ST segment elevation, and in no patients assigned to bivalirudin. In patients with ST segment elevation, major adverse cardiovascular events occurred in 118 (5.9%) assigned to bivalirudin and 129 (6.5%) assigned to heparin (rate ratio 0.90, 95% confidence interval 0.70 to 1.16; P=0.43), whereas net adverse clinical events occurred in 139 (7.0%) patients assigned to bivalirudin and 163 (8.2%) assigned to heparin (0.84, 0.67 to 1.05; P=0.13). In patients without ST segment elevation, major adverse cardiovascular events occurred in 253 (15.9%) assigned to bivalirudin and 262 (16.4%) assigned to heparin (0.97, 0.80 to 1.17; P=0.74), whereas net adverse clinical events occurred in 262 (16.5%) patients assigned to bivalirudin and 281 (17.6%) assigned to heparin (0.93, 0.77 to 1.12; P=0.43). CONCLUSIONS: A bivalirudin monotherapy strategy compared with heparin with or without glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse cardiovascular events or net adverse clinical events in patients with or without ST segment elevation.Trial Registration ClinicalTrials.gov NCT01433627. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
RCT Entities:
OBJECTIVE: To test the optimal antithrombotic regimen in patients with acute coronary syndrome. DESIGN: Randomised controlled trial. SETTING:Patients with acute coronary syndrome with and without ST segment elevation in 78 centres in Italy, the Netherlands, Spain, and Sweden. PARTICIPANTS: 7213 patients with acute coronary syndrome and planned percutaneous coronary intervention: 4010 with ST segment elevation and 3203 without ST segment elevation. The primary study results in the overall population have been reported previously. INTERVENTIONS:Patients were randomly assigned, in an open label fashion, to one of two regimens: bivalirudin with glycoprotein IIb/IIIa inhibitors restricted to procedural complications or heparin with or without glycoprotein IIb/IIIa inhibitors. MAIN OUTCOME MEASURES: Primary endpoints were the occurrence of major adverse cardiovascular events, defined as death, myocardial infarction or stroke; and net adverse clinical events, defined as major bleeding or major adverse cardiovascular events, both assessed at 30 days. Analyses were performed by the principle of intention to treat. RESULTS: Use of a glycoprotein IIb/IIIa inhibitor in patients assigned to heparin was planned at baseline in 30.7% of patients with ST segment elevation, in 10.9% without ST segment elevation, and in no patients assigned to bivalirudin. In patients with ST segment elevation, major adverse cardiovascular events occurred in 118 (5.9%) assigned to bivalirudin and 129 (6.5%) assigned to heparin (rate ratio 0.90, 95% confidence interval 0.70 to 1.16; P=0.43), whereas net adverse clinical events occurred in 139 (7.0%) patients assigned to bivalirudin and 163 (8.2%) assigned to heparin (0.84, 0.67 to 1.05; P=0.13). In patients without ST segment elevation, major adverse cardiovascular events occurred in 253 (15.9%) assigned to bivalirudin and 262 (16.4%) assigned to heparin (0.97, 0.80 to 1.17; P=0.74), whereas net adverse clinical events occurred in 262 (16.5%) patients assigned to bivalirudin and 281 (17.6%) assigned to heparin (0.93, 0.77 to 1.12; P=0.43). CONCLUSIONS: A bivalirudin monotherapy strategy compared with heparin with or without glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse cardiovascular events or net adverse clinical events in patients with or without ST segment elevation.Trial Registration ClinicalTrials.gov NCT01433627. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Sukhdeep Bhogal; Debabrata Mukherjee; Jayant Bagai; Huu T Truong; Hemang B Panchal; Ghulam Murtaza; Mustafa Zaman; Rajesh Sachdeva; Timir K Paul Journal: Cardiovasc Hematol Disord Drug Targets Date: 2020