TY - JOUR
T1 - A controlled trial of rivaroxaban after transcatheter aortic-valve replacement
AU - GALILEO Investigators
AU - Dangas, George D.
AU - Tijssen, Jan G.P.
AU - Wöhrle, Jochen
AU - Søndergaard, Lars
AU - Gilard, Martine
AU - Möllmann, Helge
AU - Makkar, Raj R.
AU - Herrmann, Howard C.
AU - Giustino, Gennaro
AU - Baldus, Stephan
AU - de Backer, Ole
AU - Guimarães, Ana H.C.
AU - Gullestad, Lars
AU - Kini, Annapoorna
AU - von Lewinski, Dirk
AU - Mack, Michael
AU - Moreno, Raúl
AU - Schäfer, Ulrich
AU - Seeger, Julia
AU - Tchétché, Didier
AU - Thomitzek, Karen
AU - Valgimigli, Marco
AU - Vranckx, Pascal
AU - Welsh, Robert C.
AU - Wildgoose, Peter
AU - Volkl, Albert A.
AU - Zazula, Ana
AU - van Amsterdam, Ronald G.M.
AU - Mehran, Roxana
AU - Windecker, Stephan
N1 - Funding Information:
The trial was supported by the sponsors, Bayer and Janssen Pharmaceuticals. The sponsors and the academic investigators designed and supervised the trial, which was executed with the as- sistance of the two clinical research organizations, Cardialysis (Rotterdam, the Netherlands) and the Center for Interventional Cardiovascular Research and Clinical Trials (Mount Sinai Hospital, New York). The executive committee included members of the academic leadership and the sponsors. Data analyses were conducted by DATAN (Havix-beck, Germany). An independent data and safety monitoring board provided oversight by periodically reviewing all reported serious adverse events. The first, second, and last authors wrote the first draft of the manuscript and made the decision to submit it for publication. All the authors reviewed and critiqued subsequent drafts and vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol. (Additional information about trial organization is provided in the Supplementary Appendix, available at NEJM.org.)
Funding Information:
Supported by Bayer in collaboration with Janssen Pharmaceuticals. Dr. Dangas reports receiving lecture fees from Bayer, receiving grant support, paid to his institution, and lecture fees from Daiichi Sankyo, and previously holding equity in Medtronic; Dr. Möllmann, receiving lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer; Dr. Makkar, receiving grant support, consulting fees, and travel support from Abbott Vascular, grant support, lecture fees, and travel support from Edwards Lifesciences, and grant support and consulting fees from Medtronic and Boston Scientific; Dr. Herrmann, receiving grant support, paid to his institution, from Abbott Vascular and Boston Scientific and grant support, paid to his institution, and consulting fees from Edwards Lifesciences and Medtronic; Dr. Giustino, receiving consulting fees from Bristol-Myers Squibb/Pfizer; Dr. De Backer, receiving lecture fees from Boston Scientific; Dr. Guimarães, being employed by Cardialysis; Dr. Mack, serving as a trial coprimary investigator for Edwards Lifesciences and Abbott Vascular and serving as a study chair for Medtronic; Dr. Schäfer, receiving grant support from the Medicines Company; Dr. Thomitzek, being employed by and holding stock in Bayer; Dr. Valgimigli, receiving lecture fees from AstraZeneca, Alvimedica/ CID, Vifor Pharma, and Medscape, grant support and lecture fees from Terumo, consulting fees and lecture fees from Abbott Vascular, Bayer, and Bristol-Myers Squibb, and consulting fees from Daiichi Sankyo, Opsens, CoreFLOW, Idorsia Pharmaceuticals, and iVascular; Dr. Vranckx, receiving fees for serving on a speakers bureau from Daiichi Sankyo, lecture fees from AstraZeneca, and fees for serving on a steering committee and travel support from CSL Behring; Dr. Welsh, receiving grant support and honoraria from AstraZeneca, Bayer, and Boehringer Ingelheim; Dr. Wildgoose, being employed by and holding stock in Janssen Pharmaceuticals; Dr. Volkl, being employed by Janssen Pharmaceuticals; Dr. van Amsterdam, being employed by Cardialysis; Dr. Zazula, being employed by Bayer; Dr. Mehran, receiving advisory board fees and consulting fees from Sanofi-Aventis and Janssen, receiving lecture fees from Bayer, receiving grant support, paid to her institution, and lecture fees from Daiichi Sankyo, and previously holding equity in Medtronic; and Dr. Windecker, receiving grant support, paid to his institution, advisory board fees, and travel support from Amgen and grant support, paid to his institution, from Abbott Vascular, Bayer, Bristol-Myers Squibb, CSL Behring, Boston Scientific, Biotronik, Medtronic, Edwards Lifesciences, Polares Medical, and Sinomed. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Publisher Copyright:
Copyright © 2019 Massachusetts Medical Society.
PY - 2020/1/9
Y1 - 2020/1/9
N2 - BACKGROUND Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P=0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P=0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy.
AB - BACKGROUND Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P=0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P=0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy.
UR - http://www.scopus.com/inward/record.url?scp=85075993796&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1911425
DO - 10.1056/NEJMoa1911425
M3 - Article
C2 - 31733180
AN - SCOPUS:85075993796
SN - 0028-4793
VL - 382
SP - 120
EP - 129
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 2
ER -