학술논문
Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation 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).
Document Type
Academic Journal
Author
Halperin JL; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.). jonathan.halperin@mssm.edu.; Hankey GJ; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Wojdyla DM; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Piccini JP; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Lokhnygina Y; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Patel MR; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Breithardt G; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Singer DE; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Becker RC; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Hacke W; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Paolini JF; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Nessel CC; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Mahaffey KW; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Califf RM; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).; Fox KA; From Icahn School of Medicine at Mount Sinai, New York, NY (J.L.H.); School of Medicine and Pharmacology, University of Western Australia School of Medicine and Pharmacology, Perth, Australia (G.J.H.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (D.M.W., J.P.P., Y.L., M.R.P.); University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston, MA (D.E.S.); University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.); Ruprecht-Karls University, Heidelberg, Germany (W.H.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Stanford University School of Medicine, Stanford, CA (K.W.M.); Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).
Source
Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0147763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4539 (Electronic) Linking ISSN: 00097322 NLM ISO Abbreviation: Circulation Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin 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). This prespecified secondary analysis compares outcomes in older and younger patients.
Methods and Results: There were 6229 patients (44%) aged ≥75 years with atrial fibrillation and ≥2 stroke risk factors randomized to warfarin (target international normalized ratio=2.0-3.0) or rivaroxaban (20 mg daily; 15 mg if creatinine clearance <50 mL/min), double blind. The primary end point was stroke and systemic embolism by intention to treat. Over 10 866 patient-years, older participants had more primary events (2.57% versus 2.05%/100 patient-years; P=0.0068) and major bleeding (4.63% versus 2.74%/100 patient-years; P<0.0001). Stroke/systemic embolism rates were consistent among older (2.29% rivaroxaban versus 2.85% warfarin per 100 patient-years; hazard ratio=0.80; 95% confidence interval, 0.63-1.02) and younger patients (2.00% versus 2.10%/100 patient-years; hazard ratio=0.95; 95% confidence interval, 0.76-1.19; interaction P=0.313), as were major bleeding rates (≥75 years: 4.86% rivaroxaban versus 4.40% warfarin per 100 patient-years; hazard ratio=1.11; 95% confidence interval, 0.92-1.34; <75 years: 2.69% versus 2.79%/100 patient-years; hazard ratio=0.96; 95% confidence interval, 0.78-1.19; interaction P=0.336). Hemorrhagic stroke rates were similar in both age groups; there was no interaction between age and rivaroxaban response.
Conclusions: Elderly patients had higher stroke and major bleeding rates than younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly.
(© 2014 American Heart Association, Inc.)
Methods and Results: There were 6229 patients (44%) aged ≥75 years with atrial fibrillation and ≥2 stroke risk factors randomized to warfarin (target international normalized ratio=2.0-3.0) or rivaroxaban (20 mg daily; 15 mg if creatinine clearance <50 mL/min), double blind. The primary end point was stroke and systemic embolism by intention to treat. Over 10 866 patient-years, older participants had more primary events (2.57% versus 2.05%/100 patient-years; P=0.0068) and major bleeding (4.63% versus 2.74%/100 patient-years; P<0.0001). Stroke/systemic embolism rates were consistent among older (2.29% rivaroxaban versus 2.85% warfarin per 100 patient-years; hazard ratio=0.80; 95% confidence interval, 0.63-1.02) and younger patients (2.00% versus 2.10%/100 patient-years; hazard ratio=0.95; 95% confidence interval, 0.76-1.19; interaction P=0.313), as were major bleeding rates (≥75 years: 4.86% rivaroxaban versus 4.40% warfarin per 100 patient-years; hazard ratio=1.11; 95% confidence interval, 0.92-1.34; <75 years: 2.69% versus 2.79%/100 patient-years; hazard ratio=0.96; 95% confidence interval, 0.78-1.19; interaction P=0.336). Hemorrhagic stroke rates were similar in both age groups; there was no interaction between age and rivaroxaban response.
Conclusions: Elderly patients had higher stroke and major bleeding rates than younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly.
(© 2014 American Heart Association, Inc.)