New Oral Xa inhibitor- warfarin can go now?

Keeping with my last post this weeks NEJM gives us 2 randomized, double-blind, placebo-controlled trials comparing the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus enoxaparin, a LMWH, in preventing VTE after 2 orthopedic surgeries. Rivar-oxapan is direct Factor Xa inhibitor. You see a cartoon of its target of action here..Click on rivaroxaban...


Current options for extended VTE prophylaxis are limited to LMWH, which must be administered subcutaneously, and VKAs such as warfarin, which have unpredictable pharmacologic effects,numerous food and drug interactions andrequire frequent laboratory monitoring. One can begin to see the possible advantages, both for the doctor as well as patient, of giving a once daily, oral medication that does not need lab monitoring. The first study, by Eriksson and Borris et al, compared rivaroxaban with enoxaparin for extended VTE prophylaxis in patients undergoing total hip arthroplasty. About 4500 patients were assigned to receive either 10 mg of oral rivaroxaban once daily, beginning after surgery, or 40 mg of enoxaparin subcutaneously once daily, beginning the evening before surgery. The primary efficacy outcome was the composite of DVT (either symptomatic or detected by bilateral venography), nonfatal pulmonary embolism, or death from any cause at 36 days. This outcome occurred in 1.1% in the rivaroxaban group and 3.7% in the enoxaparin group, a significant difference with an absolute risk reduction (ARR) of 2.6% and a number needed to treat (NNT) of approximately 38. The secondary outcome, major VTE, occurred in 0.2% in the rivaroxaban group and 2.0% in the enoxaparin group, also a significant difference with an ARR of 1.7% and a NNT of approximately 59. The primary safety outcome, major bleeding, was rare and similar in both groups. The second trial, authored by Lassen and Ageno et al, compared rivaroxaban with enoxaparin in preventing VTE after total knee arthroplasty. This study assigned approximately 2500 patients to receive either 10mg of oral rivaroxaban once daily, beginning 6 to 8 hours after surgery, or subcutaneous enoxaparin, 40 mg once daily, beginning 12 hours before surgery. The primary outcome was again the composite of any DVT, nonfatal pulmonary embolism, or death from any cause within 13 to 17 days after surgery. This outcome occurred in 9.6% who received rivaroxaban and 18.9% who received enoxaparin, a significant difference with an ARR of 9.2% and NNT of around 11. Major VTE, a secondary outcome, occurred much less often: 1.0% of patients given rivaroxaban and 2.6% of patients given enoxaparin. This difference remained significant with an ARR of 1.6% and NNT of around 63. Safety profiles were again similar. While longer follow-up data will likely be needed to assess efficacy and safety, this new drug shows promise for VTE prophylaxis following these orthopedic procedures that are frequently complicated by post-operative thrombotic events.
Links to
paper 1
paper 2