Alex C Spyropoulos1, Walter Ageno1, Gregory W Albers1, C Gregory Elliott1, Jonathan L Halperin1, William R Hiatt1, Gregory A Maynard1, P Gabriel Steg1, Jeffrey I Weitz1, Eunyoung Suh1, Theodore E Spiro1, Elliot S Barnathan1, Gary E Raskob1. 1. From the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Feinstein Institute for Medical Research, and the Department of Medicine, Anticoagulation and Clinical Thrombosis Services, Northwell Health at Lenox Hill Hospital (A.C.S.), and the Cardiovascular Institute, Mount Sinai Medical Center (J.L.H.) - all in New York; the Department of Medicine and Surgery, University of Insubria, Varese, Italy (W.A.); the Stanford Stroke Center, Stanford University Medical Center, Stanford (G.W.A.), and the University of California at Davis, Sacramento (G.A.M.) - both in California; the Department of Medicine, Intermountain Medical Center, and Department of Medicine, University of Utah, Salt Lake City (C.G.E.); Division of Cardiology, University of Colorado School of Medicine, and CPC Clinical Research, Aurora (W.R.H.); Département Hospitalo-Universitaire FIRE (Fibrose Inflammation Remodelage), University Paris Diderot, Assistance Publique-Hôpitaux de Paris, and INSERM Unité 1148, Paris (P.G.S.); Imperial College, Royal Brompton Hospital, London (P.G.S.); McMaster University and the Thrombosis and Atherosclerosis Research Institute - both in Hamilton, ON, Canada (J.I.W.); Janssen Research and Development, Raritan (E.S., E.S.B.), and the Thrombosis and Hematology Therapeutic Area, Clinical Development, Pharmaceuticals, Bayer U.S., Whippany (T.E.S.) - both in New Jersey; and the College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
Abstract
BACKGROUND:Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS: In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma d-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS:Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. (Funded by Janssen Research and Development; MARINER ClinicalTrials.gov number, NCT02111564 .).
RCT Entities:
BACKGROUND:Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS: In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma d-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS:Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. (Funded by Janssen Research and Development; MARINER ClinicalTrials.gov number, NCT02111564 .).
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