George D Dangas1, Thierry Lefèvre2, Christian Kupatt3, Didier Tchetche4, Ulrich Schäfer5, Nicolas Dumonteil6, John G Webb7, Antonio Colombo8, Stephan Windecker9, Jurriën M Ten Berg10, David Hildick-Smith11, Roxana Mehran12, Peter Boekstegers13, Axel Linke14, Christophe Tron15, Eric Van Belle16, Anita W Asgar17, Andreas Fach18, Raban Jeger19, Gennaro Sardella20, Hans Ulrich Hink21, Oliver Husser22, Eberhard Grube23, Efthymios N Deliargyris24, Ilknur Lechthaler25, Debra Bernstein24, Peter Wijngaard25, Prodromos Anthopoulos25, Christian Hengstenberg26. 1. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: george.dangas@mountsinai.org. 2. Institut Cardio Vasculaire Paris Sud, Hôpital Privé Jacques Cartier, Massy, France. 3. LMU Munich, Munich, Germany. 4. Clinique Pasteur, Toulouse, France. 5. University Heart Center, Hamburg, Germany, and Asklepios Clinics St. Georg, Hamburg, Germany. 6. CHU Rangueil, Toulouse, France. 7. St. Paul's Hospital, Vancouver, British Columbia, Canada. 8. San Raffaele Hospital, Milan, Italy. 9. Department of Cardiology, Bern University Hospital, Bern, Switzerland. 10. St. Antonius Ziekenhuis, Nieuwegein, the Netherlands. 11. Sussex Cardiac Centre-Brighton & Sussex University Hospitals NHS Trust, Brighton, East Sussex, United Kingdom. 12. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 13. Helios Heart Center Siegburg, Siegburg, Germany. 14. Universität Leipzig, Herzzentrum, Leipzig, Germany. 15. CHU de Rouen, Rouen, France. 16. Department of Cardiology and INSERM UMR 1011, University Hospital, and CHRU Lille, Lille, France. 17. Institut de Cardiologie de Montreal, Montreal, Quebec, Canada. 18. Klinikum links der Weser Bremen, Bremen, Germany. 19. Cardiology University Hospital Basel, Basel, Switzerland. 20. Policlinico Umberto I, Rome, Italy. 21. Universitätsmedizin Mainz, Mainz, Germany. 22. Deutsches Herzzentrum München, Technische Universität München, Germany. 23. Universitaetsklinikum Bonn, Bonn, Germany. 24. The Medicines Company, Parsippany, New Jersey. 25. The Medicines Company, Zurich, Switzerland. 26. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany, and Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
Abstract
BACKGROUND: Anticoagulation is required during transcatheter aortic valve replacement (TAVR) procedures. Although an optimal regimen has not been determined, heparin is mainly used. Direct thrombin inhibition with bivalirudin may be an effective alternative to heparin as the procedural anticoagulant agent in this setting. OBJECTIVES: The goal of this study was to determine whether bivalirudin offers an alternative to heparin as the procedural anticoagulant agent in patients undergoing TAVR. METHODS: A total of 802 patients with aortic stenosis were randomized to undergo transfemoral TAVR with bivalirudin versus unfractionated heparin during the procedure. The 2 primary endpoints were major bleeding within 48 h or before hospital discharge (whichever occurred first) and 30-day net adverse clinical events, defined as the combination of major adverse cardiovascular events (all-cause mortality, myocardial infarction, or stroke) and major bleeding. RESULTS: Anticoagulation with bivalirudin versus heparin did not meet superiority because it did not result in significantly lower rates of major bleeding at 48 h (6.9% vs. 9.0%; relative risk: 0.77; 95% confidence interval [CI]: 0.48 to 1.23; p = 0.27) or net adverse cardiovascular events at 30 days (14.4% vs. 16.1%; relative risk: 0.89; 95% CI: 0.64 to 1.24; risk difference: -1.72; 95% CI: -6.70 to 3.25; p = 0.50); regarding the latter, the prespecified noninferiority hypothesis was met (pnoninferiority < 0.01). Rates of major adverse cardiovascular events at 48 h were not significantly different (3.5% vs. 4.8%; relative risk: 0.73; 95% CI: 0.37 to 1.43; p = 0.35). At 48 h, the bivalirudin group had significantly fewer myocardial infarctions but more acute kidney injury events than the heparin group; at 30 days, these differences were no longer significant. CONCLUSIONS: In this randomized trial of TAVR procedural pharmacotherapy, bivalirudin did not reduce rates of major bleeding at 48 h or net adverse cardiovascular events within 30 days compared with heparin. Although superiority was not shown, the noninferiority hypothesis was met with respect to the latter factor. Given the lower cost, heparin should remain the standard of care, and bivalirudin can be an alternative anticoagulant option in patients unable to receive heparin in TAVR. (International, Multi-center, Open-label, Randomized Controlled Trial in Patients Undergoing TAVR to Determine the Treatment Effect [Both Safety and Efficacy] of Using Bivalirudin Instead of UFH [BRAVO-2/3]; NCT01651780).
RCT Entities:
BACKGROUND: Anticoagulation is required during transcatheter aortic valve replacement (TAVR) procedures. Although an optimal regimen has not been determined, heparin is mainly used. Direct thrombin inhibition with bivalirudin may be an effective alternative to heparin as the procedural anticoagulant agent in this setting. OBJECTIVES: The goal of this study was to determine whether bivalirudin offers an alternative to heparin as the procedural anticoagulant agent in patients undergoing TAVR. METHODS: A total of 802 patients with aortic stenosis were randomized to undergo transfemoral TAVR with bivalirudin versus unfractionated heparin during the procedure. The 2 primary endpoints were major bleeding within 48 h or before hospital discharge (whichever occurred first) and 30-day net adverse clinical events, defined as the combination of major adverse cardiovascular events (all-cause mortality, myocardial infarction, or stroke) and major bleeding. RESULTS: Anticoagulation with bivalirudin versus heparin did not meet superiority because it did not result in significantly lower rates of major bleeding at 48 h (6.9% vs. 9.0%; relative risk: 0.77; 95% confidence interval [CI]: 0.48 to 1.23; p = 0.27) or net adverse cardiovascular events at 30 days (14.4% vs. 16.1%; relative risk: 0.89; 95% CI: 0.64 to 1.24; risk difference: -1.72; 95% CI: -6.70 to 3.25; p = 0.50); regarding the latter, the prespecified noninferiority hypothesis was met (pnoninferiority < 0.01). Rates of major adverse cardiovascular events at 48 h were not significantly different (3.5% vs. 4.8%; relative risk: 0.73; 95% CI: 0.37 to 1.43; p = 0.35). At 48 h, the bivalirudin group had significantly fewer myocardial infarctions but more acute kidney injury events than the heparin group; at 30 days, these differences were no longer significant. CONCLUSIONS: In this randomized trial of TAVR procedural pharmacotherapy, bivalirudin did not reduce rates of major bleeding at 48 h or net adverse cardiovascular events within 30 days compared with heparin. Although superiority was not shown, the noninferiority hypothesis was met with respect to the latter factor. Given the lower cost, heparin should remain the standard of care, and bivalirudin can be an alternative anticoagulant option in patients unable to receive heparin in TAVR. (International, Multi-center, Open-label, Randomized Controlled Trial in Patients Undergoing TAVR to Determine the Treatment Effect [Both Safety and Efficacy] of Using Bivalirudin Instead of UFH [BRAVO-2/3]; NCT01651780).
Authors: Christian Frerker; Tobias Schmidt; Max M Meertens; Sascha Macherey; Sebastiaan Asselberghs; Samuel Lee; Jan Hendrik Schipper; Barend Mees; Ingo Eitel; Stephan Baldus Journal: Clin Res Cardiol Date: 2022-03-17 Impact factor: 6.138