Author + information
- Received November 19, 2017
- Revision received January 11, 2018
- Accepted January 12, 2018
- Published online March 12, 2018.
- Giuseppe Gargiulo, MDa,b,
- Greta Carrara, Statc,
- Enrico Frigoli, MDa,
- Pascal Vranckx, MD, PhDd,
- Sergio Leonardi, MD, MHSe,
- Nestor Ciociano, PharmDf,
- Gianluca Campo, MD, PhDg,h,
- Ferdinando Varbella, MDi,
- Paolo Calabrò, MD, PhDj,
- Stefano Garducci, MDk,
- Alessandro Iannone, MDl,
- Carlo Briguori, MD, PhDm,
- Giuseppe Andò, MD, PhDn,
- Gabriele Crimi, MDd,o,
- Ugo Limbruno, MDp,
- Roberto Garbo, MDq,
- Paolo Sganzerla, MDr,
- Filippo Russo, MDs,
- Alessandro Lupi, MDt,
- Bernardo Cortese, MDu,v,
- Arturo Ausiello, MDw,
- Salvatore Ierna, MDx,
- Giovanni Esposito, MD, PhDb,
- Dennis Zavalloni, MDy,
- Andrea Santarelli, MDz,
- Gennaro Sardella, MDaa,
- Simone Tresoldi, MDbb,
- Nicoletta de Cesare, MDcc,
- Alessandro Sciahbasi, MD, PhDdd,
- Antonio Zingarelli, MDee,
- Paolo Tosi, MDff,
- Arnoud van ’t Hof, MD, PhDgg,
- Elmir Omerovic, MDhh,
- Salvatore Brugaletta, MDii,
- Stephan Windecker, MDa and
- Marco Valgimigli, MD, PhDa,∗ ()
- aDepartment of Cardiology, Bern University Hospital, Bern, Switzerland
- bDepartment of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy
- cAdvice Pharma Group S.r.l., Milan, Italy
- dDepartment of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Jessa Ziekenhuis, and Faculty of Medicine and Life Sciences Hasselt University, Hasselt, Belgium
- eSC Terapia Intensiva Cardiologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- fEUSTRATEGY Association, Forli’, Italy
- gCardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
- hMaria Cecilia Hospital, GVM Care and Research, Cotignola (RA), Italy
- iCardiology Unit, Ospedali Riuniti di Rivoli, ASL Torino 3, Turin, Italy
- jDivision of Cardiology, Department of Cardiothoracic Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
- kStruttura complessa di Cardiologia ASST di Vimercate, Italy
- lDepartment of Cardiology, ASL3 Ospedale Villa Scassi, Genoa, Italy
- mInterventional Cardiology Unit, Clinica Mediterranea, Naples, Italy
- nAzienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, University of Messina, Messina, Italy
- oSC Cardiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- pUO Cardiologia, Azienda USL Toscana Sudest, Grosseto, Italy
- qInterventional Cardiology Unit, Ospedale San Giovanni Bosco, Turin, Italy
- rASST Bergamo ovest, Ospedale di Treviglio (BG), Italy
- sCardiovascular Interventional Unit, Cardiology Department, S.Anna Hospital, Como, Italy
- tUniversity Hospital “Maggiore della Carità”, Novara, Italy
- uASST Fatebenefratelli-Sacco, Milan, Italy
- vFondazione Monasterio-CNR-Regione Toscana, Toscana, Italy
- wCasa di Cura Villa Verde, Taranto, Italy
- xSimple Departmental Emodynamic Structure, Ospedale Sirai–Carbonia, Carbonia, Italy
- yHumanitas Research Hospital, IRCCS, Rozzano, Italy
- zCardiovascular Department, Infermi Hospital, Rimini, Italy
- aaDepartment of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Policlinico Umberto I, “Sapienza”, University of Rome, Rome, Italy
- bbStruttura complessa di Emodinamica, ASST Monza, Ospedale di Desio, Italy
- ccPoliclinico San Marco, Zingonia, Italy
- ddInterventional Cardiology, Sandro Pertini Hospital, Rome, Italy
- eeClinic of Cardiovascular Disease, IRCCS Policlinico San Martino, Genoa, Italy
- ffMater Salutis Hospital-Legnago, Verona, Italy
- ggMaastricht University Medical Center, and Zuyderland MC, Maastricht, the Netherlands
- hhSahlgrenska University Hospital, Göteborg, Sweden
- iiClinic Cardiovascular Institute, University Hospital Clinic, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
- ↵∗Address for correspondence:
Dr. Marco Valgimigli, Department of Cardiology, Bern University Hospital, Freiburgstrasse 4, CH-3010, Bern, Switzerland.
Background Contrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs).
Objectives This study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management.
Methods In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding).
Results Among 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p = 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFH+GPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess site−related events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site.
Conclusions In patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627)
The trial was sponsored by the Società Italiana di Cardiologia Invasiva (GISE, a non-profit organization), which received grant support from The Medicines Company and TERUMO. This substudy did not receive any direct or indirect funding. Dr. Gargiulo has received research grant support from the Cardiopath PhD program. Dr. Vranckx has received speaking or consulting fees from Bayer Health Care and Daiichi-Sankyo. Dr. Leonardi has received grants and personal fees from AstraZeneca; and personal fees from Chiesi, Daiichi-Sankyo, and The Medicines Company. Dr. Varbella has received speaking or consulting fees from Boeringher Ingelheim, Daiichi-Sankyo, Bayer, Pfizer, AstraZeneca, OrbusNeich, Biosensors, AbbottVascular, Amgen, and Bristol-Myers Squibb; and has received grants from Medtronic, Boston Scientific, Abbott, St. Jude, Biosensors, CID Alvimedica, and Abbott Vascular. Dr. Andò has received nonfinancial support from Terumo during the study; personal fees from Daiichi-Sankyo, Pfizer, and AstraZeneca; and personal fees and nonfinancial support from Bayer. Dr. Cortese has received research grants from AB Medica, Abbott, St. Jude Medical, and Stentys; and personal fees from Abbott, AstraZeneca, Daiichi-Sankyo, and Eli Lilly and Stentys. Dr Sciahbasi has served as advisory board member for Bayer HealthCare. Dr van’t Hof has received speaker fees from The Medicines Company; has received unrestricted grants from Medtronic and AstraZeneca; and has served as Executive Board member of the EUROMAX trial. Dr. Omervoic has been a member of the advisory board for Boston Scientific; and has received a research grant from AstraZeneca. Dr. Windecker has received research grants from Abbott, Amgen, Bracco, Boston Scientific, Biotronick, St. Jude, and Terumo. Dr. Valgimigli has received grants from The Medicines Company, Terumo, and AstraZeneca; and has received personal fees from Terumo, St. Jude Vascular, and Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 19, 2017.
- Revision received January 11, 2018.
- Accepted January 12, 2018.
- 2018 American College of Cardiology Foundation
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