title: Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial.
abstract: OBJECTIVE
  We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial.
  
  
  RESULTS
  ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55-1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75-1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05-1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94-1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban.
  
  
  CONCLUSIONS
  Many patients with 'non-valvular atrial fibrillation' have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants.
authors.affiliation: Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Von-Esmarch-Strasse 117, Münster D-48149, Germany g.breithardt@uni-muenster.de.
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.affiliation: Department of Cardiovascular Medicine, Division of Adult Congenital and Valvular Heart Disease, University Hospital Münster, Münster, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Baumgartner
authors.affiliation: Bayer Healthcare Pharmaceuticals, L.P., Whippany, NJ, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Berkowitz
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: The Cardiovascular Institute, Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.affiliation: Clinical Epidemiology Unit, General Medicine Division, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: University of Edinburgh, and Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.affiliation: Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001022:Aortic Valve Insufficiency / Q000150:complications* / Q000401:mortality; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D065427:Factor Xa Inhibitors / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008944:Mitral Valve Insufficiency / Q000150:complications* / Q000401:mortality; D009025:Morpholines / Q000627:therapeutic use*; D000069552:Rivaroxaban; D020521:Stroke / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014859:Warfarin; D000069552:Rivaroxaban
keywords: Anticoagulants; Fibrillation; Heart diseases; Regurgitation; Stenosis