Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement: The Randomized BRAVO-3 Trial

TY - JOUR

T1 - Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement: The Randomized BRAVO-3 Trial

AU - Dangas, George D

AU - Lefèvre, Thierry

AU - Kupatt, Christian

AU - Tchetche, Didier

AU - Schäfer, Ulrich

AU - Dumonteil, Nicolas

AU - Webb, John G

AU - Colombo, Antonio

AU - Windecker, Stephan

AU - Ten Berg, Jurriën M

AU - Hildick-Smith, David

AU - Mehran, Roxana

AU - Boekstegers, Peter

AU - Linke, Axel

AU - Tron, Christophe

AU - Van Belle, Eric

AU - Asgar, Anita W

AU - Fach, Andreas

AU - Jeger, Raban

AU - Sardella, Gennaro

AU - Hink, Hans Ulrich

AU - Husser, Oliver

AU - Grube, Eberhard

AU - Deliargyris, Efthymios N

AU - Lechthaler, Ilknur

AU - Bernstein, Debra

AU - Wijngaard, Peter

AU - Anthopoulos, Prodromos

AU - Hengstenberg, Christian

AU - BRAVO-3 Investigators

N1 - Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PY - 2015/12/29

Y1 - 2015/12/29

N2 - 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).

AB - 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).

KW - Aged, 80 and over

KW - Anticoagulants/administration & dosage

KW - Antithrombins/administration & dosage

KW - Aortic Valve Stenosis/diagnosis

KW - Dose-Response Relationship, Drug

KW - Echocardiography

KW - Europe/epidemiology

KW - Female

KW - Follow-Up Studies

KW - Heparin/administration & dosage

KW - Hirudins/administration & dosage

KW - Humans

KW - Incidence

KW - Male

KW - Peptide Fragments/administration & dosage

KW - Postoperative Hemorrhage/chemically induced

KW - Recombinant Proteins/administration & dosage

KW - Retrospective Studies

KW - Survival Rate/trends

KW - Thromboembolism/prevention & control

KW - Transcatheter Aortic Valve Replacement

KW - Treatment Outcome

KW - United States/epidemiology

U2 - 10.1016/j.jacc.2015.10.003

DO - 10.1016/j.jacc.2015.10.003

M3 - SCORING: Journal article

C2 - 26477635

VL - 66

SP - 2860

EP - 2868

JO - J AM COLL CARDIOL

JF - J AM COLL CARDIOL

SN - 0735-1097

IS - 25

ER -