Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism.
Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin.



In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding.



A total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups.



Among patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439 .).
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Jeffrey I
JI
Weitz
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Anthonie W A
AWA
Lensing
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Martin H
MH
Prins
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Rupert
R
Bauersachs
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Jan
J
Beyer-Westendorf
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Henri
H
Bounameaux
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Timothy A
TA
Brighton
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Alexander T
AT
Cohen
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Bruce L
BL
Davidson
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Hervé
H
Decousus
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Maria C S
MCS
Freitas
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Gerlind
G
Holberg
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Ajay K
AK
Kakkar
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Lloyd
L
Haskell
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Bonno
B
van Bellen
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Akos F
AF
Pap
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Scott D
SD
Berkowitz
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Peter
P
Verhamme
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Philip S
PS
Wells
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) - both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) - all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King's College London (J.B.-W.), the Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) - all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d'Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.).
Paolo
P
Prandoni
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000069552:Rivaroxaban / Q000008:administration & dosage* / Q000009:adverse effects; D055502:Secondary Prevention; D054556:Venous Thromboembolism / Q000401:mortality / Q000517:prevention & control*
D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D000069552:Rivaroxaban; D001241:Aspirin