Rivaroxaban versus enoxaparin/vitamin K antagonist therapy in patients with venous thromboembolism and renal impairment.
BACKGROUND
Patients with renal impairment receiving classical anticoagulation for venous thromboembolism (VTE) are at increased risk of bleeding and possibly pulmonary embolism. We examined the efficacy and safety of oral rivaroxaban in patients with VTE with and without renal impairment.


METHODS
Prespecified subgroup analysis of the EINSTEIN DVT and EINSTEIN PE studies comparing fixed-dose rivaroxaban with enoxaparin/a vitamin K antagonist (VKA), performed in 8246 patients enrolled from 2007 to 2011 in 314 hospitals.


RESULTS
Outcomes were recurrent VTE and major or clinically relevant nonmajor bleeding in patients with normal renal function (n = 5569; 67.3%) or mild (n = 2037; 24.6%), moderate (n = 636; 7.7%), or severe (n = 21; 0.3%) renal impairment. Rates of recurrent VTE were 1.8%, 2.8%, 3.3%, and 4.8% in patients with normal renal function and mild, moderate, and severe renal impairment, respectively (ptrend = 0.001). Hazard ratios for recurrent VTE were similar between treatment groups across renal function categories (pinteraction = 0.72). Major bleeding in rivaroxaban recipients occurred in 0.8%, 1.4%, 0.9%, and 0%, respectively (ptrend = 0.50). Respective rates in enoxaparin/VKA recipients were 1.0%, 3.0%, 3.9%, and 9.1% (ptrend < 0.001). Rivaroxaban-enoxaparin/VKA hazard ratios were 0.79 (95% confidence interval [CI] 0.46-1.36) for normal renal function, 0.44 (95% CI 0.24-0.84) for mild renal impairment, and 0.23 (95% CI 0.06-0.81) for moderate renal impairment (pinteraction = 0.034).


CONCLUSIONS
Patients with symptomatic VTE and renal impairment are at increased risk of recurrent VTE. Renal impairment increased the risk of major bleeding in enoxaparin/VKA-treated patients but not in rivaroxaban-treated patients.


BACKGROUND
NCT00440193 and NCT00439777.
Department of Vascular Medicine, Klinikum Darmstadt GmbH, Grafenstraße 9, 64283 Darmstadt, Germany.
Rupert M
RM
Bauersachs
Bayer HealthCare, Wuppertal, Germany.
Anthonie Wa
AW
Lensing
University of Maastricht, Maastricht, the Netherlands.
Martin H
MH
Prins
Bayer HealthCare, Wuppertal, Germany.
Dagmar
D
Kubitza
Bayer HealthCare, Wuppertal, Germany.
Ákos F
ÁF
Pap
Université Jean Monnet, Saint-Etienne, France.
Hervé
H
Decousus
Dresden University Hospital "C.G.Carus", Dresden, Germany.
Jan
J
Beyer-Westendorf
Department of Medicine, University of Padua, Padua, Italy.
Paolo
P
Prandoni
Anticoagulants; Bleeding; Renal insufficiency; Rivaroxaban; Venous thromboembolism