A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.

Factor Xa Inhibitors; Platelet Aggregation Inhibitors; 9NDF7JZ4M3 (Rivaroxaban); A74586SNO7 (Clopidogrel); R16CO5Y76E (Aspirin); Aged; Aged, 80 and over; Aspirin/adverse effects/therapeutic use; Atrial Fibrillation/drug therapy; Cardiovascular Diseases/mortality; Clopidogrel/adverse effects/therapeutic use; Drug Therapy, Combination; Factor Xa Inhibitors/adverse effects/therapeutic use; Female; Heart Valve Prosthesis; Hemorrhage/chemically induced; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Platelet Aggregation Inhibitors/adverse effects/therapeutic use; Rivaroxaban/adverse effects/therapeutic use; Thromboembolism/mortality; Transcatheter Aortic Valve Replacement

Abstract :

[en] 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. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).

Disciplines :

Cardiovascular & respiratory systems

Author, co-author :

Dangas, George D; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

Tijssen, Jan G P; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

Wöhrle, Jochen; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

Søndergaard, Lars; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

Gilard, Martine; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

Möllmann, Helge; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

Makkar, Raj R; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

Herrmann, Howard C; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

Giustino, Gennaro; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

Baldus, Stephan; From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of

More authors (21 more)

Other collaborator :

Dangas, G D

Windecker, S

Mehran, R

Tijssen, J G P

Welsh, R C

Vranckx, P

Valgimigli, M

van Amsterdam, R G M

Thomitzek, K

Wildgoose, P

More authors (717 more)

Language :

English

Title :

A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.

Publication date :

09 January 2020

Journal title :

New England Journal of Medicine

ISSN :

0028-4793

eISSN :

1533-4406

Publisher :

Massachusetts Medical Society, Us ma

Volume :

382

Issue :

Pages :

120-129

Peer reviewed :

Peer Reviewed verified by ORBi

Funding number :

Sponsor/Bayer/International; Sponsor/Janssen Pharmaceuticals/International

Commentary :

Available on ORBi :

since 18 May 2022

Statistics

Number of views

61 (6 by ULiège)

Number of downloads

19 (1 by ULiège)

More statistics

Scopus citations^®

364

Scopus citations^®
without self-citations

299

OpenCitations

229

Bibliography

Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187-98.
Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med 2016;374:1609-20.
Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363: 1597-607.
Reardon MJ, Van Mieghem NM, Popma JJ, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med 2017;376:1321-31.
Adams DH, Popma JJ, Reardon MJ, et al. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med 2014;370:1790-8.
Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med 2019;380:1695-705.
Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med 2019;380:1706-15.
Hansson NC, Grove EL, Andersen HR, et al. Transcatheter aortic valve thrombosis: incidence, predisposing factors, and clinical implications. J Am Coll Cardiol 2016;68:2059-69.
Chakravarty T, Søndergaard L, Friedman J, et al. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. Lancet 2017;389:2383-92.
Makkar RR, Fontana G, Jilaihawi H, et al. Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N Engl J Med 2015;373:2015-24.
Puri R, Auffret V, Rodés-Cabau J. Bio-prosthetic valve thrombosis. J Am Coll Cardiol 2017;69:2193-211.
Dangas GD, Weitz JI, Giustino G, Makkar R, Mehran R. Prosthetic heart valve thrombosis. J Am Coll Cardiol 2016; 68:2670-89.
Jose J, Sulimov DS, El-Mawardy M, et al. Clinical bioprosthetic heart valve thrombosis after transcatheter aortic valve replacement: incidence, characteristics, and treatment outcomes. JACC Cardiovasc Interv 2017;10:686-97.
Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2017;38:2739-91.
Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63(22):e57-e185.
Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883-91.
Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012;366:9-19.
Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017;377:1319-30.
Windecker S, Tijssen J, Giustino G, et al. Trial design: rivaroxaban for the prevention of major cardiovascular events after transcatheter aortic valve replacement: rationale and design of the GALILEO study. Am Heart J 2017;184: 81-7.
Kappetein AP, Head SJ, Généreux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. J Am Coll Cardiol 2012;60:1438-54.
De Backer O, Dangas GD, Jilaihawi H, et al. Reduced leaflet motion after transcatheter aortic-valve replacement. N Engl J Med 2020;382:130-9.
Van Belle E, Hengstenberg C, Lefevre T, et al. Cerebral embolism during transcatheter aortic valve replacement: the BRAVO-3 MRI study. J Am Coll Cardiol 2016;68:589-99.
Dangas GD, Lefèvre T, Kupatt C, et al. Bivalirudin versus heparin anticoagulation in transcatheter aortic valve replacement: the randomized BRAVO-3 trial. J Am Coll Cardiol 2015;66:2860-8.
Dangas GD, Giustino G. Art and science of cerebrovascular event prevention after transcatheter aortic valve replacement. Circ Cardiovasc Interv 2016;9:9.
Overtchouk P, Guedeney P, Rouanet S, et al. Long-term mortality and early valve dysfunction according to anticoagulation use: the FRANCE TAVI registry. J Am Coll Cardiol 2019;73:13-21.