Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from 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).

Author(s): Sherwood MW(1), Douketis JD, Patel MR, Piccini JP, Hellkamp AS, Lokhnygina Y, Spyropoulos AC, Hankey GJ, Singer DE, Nessel CC, Mahaffey KW, Fox KA, Califf RM, Becker RC; ROCKET AF Investigators.

Affiliation(s): Author information: (1)Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, NC (M.W.S., M.R.P., J.P.P., A.S.H., Y.L., R.M.C., R.C.B.); Department of Medicine, Division of Hematology and Thromboembolism, McMaster University, Hamilton, Ontario, Canada (J.D.D.); Department of Medicine, Division of Hematology, Hofstra North Shore/LIJ School of Medicine, Lenox Hill Hospital, New York, NY (A.C.S.); School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (G.J.H.); Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ (C.C.N.); Department of Medicine, Stanford University Medical Center, Palo Alto, CA (K.W.M.); and Department of Medicine, University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).

Publication date & source: 2014, Circulation. , 129(18):1850-9

BACKGROUND: During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. METHODS AND RESULTS: 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), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32). CONCLUSIONS: TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.