Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients

In acutely ill patients, 10 days of rivaroxaban was noninferior to 10 days of enoxaparin for thromboprophylaxis. Extended-duration rivaroxaban treatment (35 days) reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding. Patients with active cancer, s...

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Published in:The New England journal of medicine Vol. 368; no. 6; pp. 513 - 523
Main Authors: Cohen, Alexander T, Spiro, Theodore E, Büller, Harry R, Haskell, Lloyd, Hu, Dayi, Hull, Russell, Mebazaa, Alexandre, Merli, Geno, Schellong, Sebastian, Spyropoulos, Alex C, Tapson, Victor
Format: Journal Article
Language:English
Published: Waltham, MA Massachusetts Medical Society 07.02.2013
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ISSN:0028-4793, 1533-4406, 1533-4406
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Abstract In acutely ill patients, 10 days of rivaroxaban was noninferior to 10 days of enoxaparin for thromboprophylaxis. Extended-duration rivaroxaban treatment (35 days) reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding. Patients with active cancer, stroke, myocardial infarction, or acute exacerbations of a variety of medical conditions are at increased risk for venous thromboembolism. 1 Prolonged immobilization and risk factors such as an age older than 75 years, chronic heart failure, a history of venous thromboembolism, and obesity can increase this risk further. 2 , 3 Randomized, controlled trials involving hospitalized patients at increased risk for venous thromboembolism have shown the benefits of administering anticoagulant agents for up to 14 days, 4 – 8 and guidelines recommend the use of unfractionated heparin, low-molecular-weight heparins, or fondaparinux in such patients. 9 There is some evidence that the risk . . .
AbstractList BACKGROUND: The clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter, randomized, double-blind trial, we evaluated the efficacy and safety of oral rivaroxaban administered for an extended period, as compared with subcutaneous enoxaparin administered for a standard period, followed by placebo. METHODS: We randomly assigned patients 40 years of age or older who were hospitalized for an acute medical illness to receive subcutaneous enoxaparin, 40 mg once daily, for 10±4 days and oral placebo for 35±4 days or to receive subcutaneous placebo for 10±4 days and oral rivaroxaban, 10 mg once daily, for 35±4 days. The primary efficacy outcomes were the composite of asymptomatic proximal or symptomatic venous thromboembolism up to day 10 (noninferiority test) and up to day 35 (superiority test). The principal safety outcome was the composite of major or clinically relevant nonmajor bleeding. RESULTS: A total of 8101 patients underwent randomization. A primary efficacy outcome event occurred in 78 of 2938 patients (2.7%) receiving rivaroxaban and 82 of 2993 patients (2.7%) receiving enoxaparin at day 10 (relative risk with rivaroxaban, 0.97; 95% confidence interval [CI], 0.71 to 1.31; P=0.003 for noninferiority) and in 131 of 2967 patients (4.4%) who received rivaroxaban and 175 of 3057 patients (5.7%) who received enoxaparin followed by placebo at day 35 (relative risk, 0.77; 95% CI, 0.62 to 0.96; P=0.02). A principal safety outcome event occurred in 111 of 3997 patients (2.8%) in the rivaroxaban group and 49 of 4001 patients (1.2%) in the enoxaparin group at day 10 (P<0.001) and in 164 patients (4.1%) and 67 patients (1.7%) in the respective groups at day 35 (P<0.001). CONCLUSIONS: In acutely ill medical patients, rivaroxaban was noninferior to enoxaparin for standard-duration thromboprophylaxis. Extended-duration rivaroxaban reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding. (Funded by Bayer HealthCare Pharmaceuticals and Janssen Research and Development; MAGELLAN ClinicalTrials.gov number, NCT00571649.).
In acutely ill patients, 10 days of rivaroxaban was noninferior to 10 days of enoxaparin for thromboprophylaxis. Extended-duration rivaroxaban treatment (35 days) reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding. Patients with active cancer, stroke, myocardial infarction, or acute exacerbations of a variety of medical conditions are at increased risk for venous thromboembolism. 1 Prolonged immobilization and risk factors such as an age older than 75 years, chronic heart failure, a history of venous thromboembolism, and obesity can increase this risk further. 2 , 3 Randomized, controlled trials involving hospitalized patients at increased risk for venous thromboembolism have shown the benefits of administering anticoagulant agents for up to 14 days, 4 – 8 and guidelines recommend the use of unfractionated heparin, low-molecular-weight heparins, or fondaparinux in such patients. 9 There is some evidence that the risk . . .
The clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter, randomized, double-blind trial, we evaluated the efficacy and safety of oral rivaroxaban administered for an extended period, as compared with subcutaneous enoxaparin administered for a standard period, followed by placebo. We randomly assigned patients 40 years of age or older who were hospitalized for an acute medical illness to receive subcutaneous enoxaparin, 40 mg once daily, for 10±4 days and oral placebo for 35±4 days or to receive subcutaneous placebo for 10±4 days and oral rivaroxaban, 10 mg once daily, for 35±4 days. The primary efficacy outcomes were the composite of asymptomatic proximal or symptomatic venous thromboembolism up to day 10 (noninferiority test) and up to day 35 (superiority test). The principal safety outcome was the composite of major or clinically relevant nonmajor bleeding. A total of 8101 patients underwent randomization. A primary efficacy outcome event occurred in 78 of 2938 patients (2.7%) receiving rivaroxaban and 82 of 2993 patients (2.7%) receiving enoxaparin at day 10 (relative risk with rivaroxaban, 0.97; 95% confidence interval [CI], 0.71 to 1.31; P=0.003 for noninferiority) and in 131 of 2967 patients (4.4%) who received rivaroxaban and 175 of 3057 patients (5.7%) who received enoxaparin followed by placebo at day 35 (relative risk, 0.77; 95% CI, 0.62 to 0.96; P=0.02). A principal safety outcome event occurred in 111 of 3997 patients (2.8%) in the rivaroxaban group and 49 of 4001 patients (1.2%) in the enoxaparin group at day 10 (P<0.001) and in 164 patients (4.1%) and 67 patients (1.7%) in the respective groups at day 35 (P<0.001). In acutely ill medical patients, rivaroxaban was noninferior to enoxaparin for standard-duration thromboprophylaxis. Extended-duration rivaroxaban reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding. (Funded by Bayer HealthCare Pharmaceuticals and Janssen Research and Development; MAGELLAN ClinicalTrials.gov number, NCT00571649.).
The clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter, randomized, double-blind trial, we evaluated the efficacy and safety of oral rivaroxaban administered for an extended period, as compared with subcutaneous enoxaparin administered for a standard period, followed by placebo.BACKGROUNDThe clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter, randomized, double-blind trial, we evaluated the efficacy and safety of oral rivaroxaban administered for an extended period, as compared with subcutaneous enoxaparin administered for a standard period, followed by placebo.We randomly assigned patients 40 years of age or older who were hospitalized for an acute medical illness to receive subcutaneous enoxaparin, 40 mg once daily, for 10±4 days and oral placebo for 35±4 days or to receive subcutaneous placebo for 10±4 days and oral rivaroxaban, 10 mg once daily, for 35±4 days. The primary efficacy outcomes were the composite of asymptomatic proximal or symptomatic venous thromboembolism up to day 10 (noninferiority test) and up to day 35 (superiority test). The principal safety outcome was the composite of major or clinically relevant nonmajor bleeding.METHODSWe randomly assigned patients 40 years of age or older who were hospitalized for an acute medical illness to receive subcutaneous enoxaparin, 40 mg once daily, for 10±4 days and oral placebo for 35±4 days or to receive subcutaneous placebo for 10±4 days and oral rivaroxaban, 10 mg once daily, for 35±4 days. The primary efficacy outcomes were the composite of asymptomatic proximal or symptomatic venous thromboembolism up to day 10 (noninferiority test) and up to day 35 (superiority test). The principal safety outcome was the composite of major or clinically relevant nonmajor bleeding.A total of 8101 patients underwent randomization. A primary efficacy outcome event occurred in 78 of 2938 patients (2.7%) receiving rivaroxaban and 82 of 2993 patients (2.7%) receiving enoxaparin at day 10 (relative risk with rivaroxaban, 0.97; 95% confidence interval [CI], 0.71 to 1.31; P=0.003 for noninferiority) and in 131 of 2967 patients (4.4%) who received rivaroxaban and 175 of 3057 patients (5.7%) who received enoxaparin followed by placebo at day 35 (relative risk, 0.77; 95% CI, 0.62 to 0.96; P=0.02). A principal safety outcome event occurred in 111 of 3997 patients (2.8%) in the rivaroxaban group and 49 of 4001 patients (1.2%) in the enoxaparin group at day 10 (P<0.001) and in 164 patients (4.1%) and 67 patients (1.7%) in the respective groups at day 35 (P<0.001).RESULTSA total of 8101 patients underwent randomization. A primary efficacy outcome event occurred in 78 of 2938 patients (2.7%) receiving rivaroxaban and 82 of 2993 patients (2.7%) receiving enoxaparin at day 10 (relative risk with rivaroxaban, 0.97; 95% confidence interval [CI], 0.71 to 1.31; P=0.003 for noninferiority) and in 131 of 2967 patients (4.4%) who received rivaroxaban and 175 of 3057 patients (5.7%) who received enoxaparin followed by placebo at day 35 (relative risk, 0.77; 95% CI, 0.62 to 0.96; P=0.02). A principal safety outcome event occurred in 111 of 3997 patients (2.8%) in the rivaroxaban group and 49 of 4001 patients (1.2%) in the enoxaparin group at day 10 (P<0.001) and in 164 patients (4.1%) and 67 patients (1.7%) in the respective groups at day 35 (P<0.001).In acutely ill medical patients, rivaroxaban was noninferior to enoxaparin for standard-duration thromboprophylaxis. Extended-duration rivaroxaban reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding. (Funded by Bayer HealthCare Pharmaceuticals and Janssen Research and Development; MAGELLAN ClinicalTrials.gov number, NCT00571649.).CONCLUSIONSIn acutely ill medical patients, rivaroxaban was noninferior to enoxaparin for standard-duration thromboprophylaxis. Extended-duration rivaroxaban reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding. (Funded by Bayer HealthCare Pharmaceuticals and Janssen Research and Development; MAGELLAN ClinicalTrials.gov number, NCT00571649.).
Author Büller, Harry R
Haskell, Lloyd
Schellong, Sebastian
Spiro, Theodore E
Hu, Dayi
Tapson, Victor
Cohen, Alexander T
Hull, Russell
Spyropoulos, Alex C
Mebazaa, Alexandre
Merli, Geno
Author_xml – sequence: 1
  givenname: Alexander T
  surname: Cohen
  fullname: Cohen, Alexander T
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 2
  givenname: Theodore E
  surname: Spiro
  fullname: Spiro, Theodore E
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 3
  givenname: Harry R
  surname: Büller
  fullname: Büller, Harry R
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 4
  givenname: Lloyd
  surname: Haskell
  fullname: Haskell, Lloyd
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 5
  givenname: Dayi
  surname: Hu
  fullname: Hu, Dayi
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 6
  givenname: Russell
  surname: Hull
  fullname: Hull, Russell
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 7
  givenname: Alexandre
  surname: Mebazaa
  fullname: Mebazaa, Alexandre
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 8
  givenname: Geno
  surname: Merli
  fullname: Merli, Geno
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 9
  givenname: Sebastian
  surname: Schellong
  fullname: Schellong, Sebastian
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 10
  givenname: Alex C
  surname: Spyropoulos
  fullname: Spyropoulos, Alex C
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
– sequence: 11
  givenname: Victor
  surname: Tapson
  fullname: Tapson, Victor
  organization: From King's College Hospital, London (A.T.C.); Bayer HealthCare Pharmaceuticals, Montville (T.E.S.), and Janssen Research and Development, Raritan (L.H.) — both in New Jersey; Academic Medical Center, Amsterdam (H.R.B.); People's Hospital of Peking University, Beijing (D.H.); Foothills Hospital, Calgary, AB, Canada (R.H.); Hôpital Lariboisière, Paris (A.M.); Thomas Jefferson Medical Center, Philadelphia (G.M.); Dresden-Friedrichstadt Hospital, Dresden, Germany (S.S.); Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, NY (A.C.S.); and Duke University Medical Center, Durham, NC (V.T.)
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ContentType Journal Article
Contributor Francis, C
van Zandweghe, L
Bergeron, C
Merli, G
Peters, R G J
Carroll, P
Voorend, M
Hall, S
Leizorovicz, A
Bizzacchi, J M A
Prins, M
Bauer, N C
Weidinger, F
Nessel, C
Hu, D
Dimov, D
Otten, H M
Schönherr, H-R
Cohen, A T
Jackson, D
Colquhoun, D
Lyubenov, L
Kirchmair, P
Schellong, S
Fiss, E
Hemmrich, M
Beckmann, H
Mac Gillavry, M R
Leyden, M
Fortunat, W
Caberlotto, O
Siostrzonek, P
Hull, R
Mühlhofer, E
Grand, B
van Roey, G
Hojman, M
Haskell, L
Robben, S
Balcke, P
Lowe, G
Baker, R
Garicochea, B
Mykietiuk, A
Weltermann, A
Spyropoulos, A C
Hendler, H
Fielding, L
Meng, I
Mebazaa, A
Spiro, T
Grafl, E
Mincheva, V
Desanctis, Y
Wenisch, C
Salerno, R
Gan, E
Twomey, T
Milanov, S
Büller, H
Chong, B
Müller, K
Ivanov, Y
Vanden Abeele, A
Taseva, M
Duszczyszyn, A
Striekwold, H
Limburg, M L
Soupart, A
Li, L
Erlacher, L
Delobbe, A
Blockmans, D
Brandges, D
Keil, F
van Bellen, B
Pilger, E
Jacquy, C
Popov, D
Chamone, D
Tapson, V
Kobayashi, S
Salem, H
Cavalheiro, C
Boulanger, J-M
Nenkova, S
Hendrickx, K
Atkinson, Sarah
van Hoof, M-E
Byra, W
Serisier, D
Buck, B
Bottaro, F J
Roberts, R
Rocha Moreira, R
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Issue 6
Keywords Vascular disease
Human
Medicine
Prevention
Rivaroxaban
Antithrombotic agent
Cardiovascular disease
Patient
Thrombosis
Language English
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Snippet In acutely ill patients, 10 days of rivaroxaban was noninferior to 10 days of enoxaparin for thromboprophylaxis. Extended-duration rivaroxaban treatment (35...
The clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter, randomized,...
Background The clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter,...
BACKGROUND: The clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter,...
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StartPage 513
SubjectTerms Acute Disease
Administration, Oral
Adult
Aged
Anticoagulants
Anticoagulants - adverse effects
Anticoagulants - therapeutic use
Asymptomatic
Biological and medical sciences
Double-Blind Method
Drug Administration Schedule
Enoxaparin
Enoxaparin - adverse effects
Enoxaparin - therapeutic use
Factor Xa
Factor Xa Inhibitors
Female
General aspects
Heart attacks
Hemorrhage
Hemorrhage - chemically induced
Hospitalization
Humans
Injections, Subcutaneous
Life Sciences
Male
Medical sciences
Middle Aged
Morpholines
Morpholines - adverse effects
Morpholines - therapeutic use
Prevention and actions
Public health. Hygiene
Public health. Hygiene-occupational medicine
Pulmonary embolisms
Rivaroxaban
Thiophenes
Thiophenes - adverse effects
Thiophenes - therapeutic use
Thromboembolism
Thrombosis
Ultrasonic imaging
Veins & arteries
Venous Thromboembolism
Venous Thromboembolism - epidemiology
Venous Thromboembolism - prevention & control
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Title Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients
URI https://nejm.org/doi/full/10.1056/NEJMoa1111096
https://www.ncbi.nlm.nih.gov/pubmed/23388003
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Volume 368
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