Oral rivaroxaban for symptomatic venous thromboembolism.
BACKGROUND
Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.


METHODS
We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.


RESULTS
The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11).


CONCLUSIONS
Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).
Rupert
R
Bauersachs
Scott D
SD
Berkowitz
Benjamin
B
Brenner
Harry R
HR
Buller
Hervé
H
Decousus
Alex S
AS
Gallus
Anthonie W
AW
Lensing
Frank
F
Misselwitz
Martin H
MH
Prins
Gary E
GE
Raskob
Annelise
A
Segers
Peter
P
Verhamme
Phil
P
Wells
Giancarlo
G
Agnelli
Henri
H
Bounameaux
Alexander
A
Cohen
Bruce L
BL
Davidson
Franco
F
Piovella
Sebastian
S
Schellong
D000074:Acenocoumarol / Q000009:adverse effects / Q000627:therapeutic use; D000208:Acute Disease; D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000627:therapeutic use*; D011655:Pulmonary Embolism / Q000188:drug therapy*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D054556:Venous Thromboembolism / Q000188:drug therapy; D020246:Venous Thrombosis / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014812:Vitamin K; D014859:Warfarin; D000069552:Rivaroxaban; D000074:Acenocoumarol