ASH: Oral Factor Xa Inhibitor Tops Enoxaparin for VTE after Hip Replacement

Bengt Eriksson, M.D.Sahlgrenska University Hospital Goteborg, Sweden
ATLANTA, Dec. 10 -- Venous thromboembolism after hip replacement surgery occurred 70% less often with the investigational drug rivaroxaban than with enoxaparin (Lovenox), researchers found. The risk reduction with the oral Factor Xa inhibitor occurred with no increase in bleeding, Bengt Eriksson, M.D., of Sahlgrenska University Hospital in Gothenburg, Sweden, told attendees at the American Society of Hematology meeting here. The risk of major VTE was significantly reduced, at P<0.001, and the risk of symptomatic VTE did not differ between rivaroxaban and enoxaparin.
Action Points --->
Explain to interested patients that a new oral drug reduced the risk of clots after hip replacement compared with current therapy.
Emphasize that the new therapy is not yet commercially available.
"The results to me personally were very convincing and also a big surprise," said Dr. Eriksson. "We did not only obtain noninferiority with the standard treatment but also superiority."
The search for an optimal anticoagulant began with the introduction of unfractionated heparin, a nonspecific, parenteral agent. Oral vitamin K inhibitors emerged a decade or so later but required frequent monitoring and dose adjustment, said Dr. Eriksson. Low molecular weight heparin, direct thrombin inhibitors, and first-generation Factor Xa inhibitors all required parenteral administration, which is inconvenient for out-of-hospital chronic therapy.
"There has been a clinical need for an oral, predictable, fixed-dose agent that does not require monitoring," said Dr. Eriksson.
The search for the optimal anticoagulant continued with the RECORD1 trial of rivaroxaban, the first oral inhibitor of Factor Xa. The trial involved 4,541 patients undergoing total hip replacement randomized to rivaroxaban 10 mg/day or enoxaparin 40 mg/day beginning six to eight hours after surgery.
Treatment continued to the day before scheduled venography, which averaged 36 days. Follow-up continued to day 65.
The primary efficacy endpoint was the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality. Patients randomized to enoxaparin had an endpoint rate of 3.7% compared with 1.1% with rivaroxaban (P<0.001).
Major bleeding, the principal safety endpoint, occurred in 0.09% of enoxaparin patients and 0.27% of rivaroxaban patients. The difference was not statistically significant.
Major VTE, a secondary endpoint, was 2% with enoxaparin and 0.2% with rivaroxaban, an 88% reduction in relative risk (P<0.001). Symptomatic VTE occurred in 0.5% of enoxaparin patients and 0.3% of rivaroxaban, a nonsignificant difference.
Patients treated with either anticoagulant had similar rates of non-bleeding adverse events, including elevated liver enzymes and elevated bilirubin.
"I think it is quite obvious that this new regimen, this new oral Factor Xa inhibitor regimen, will help my colleagues in surgery to use extended therapy to prevent thrombosis in a more convenient way," said Dr. Eriksson. "I think this will help both physicians and patients."
All of the authors are consultants for Bayer HealthCare, which supported the study. Three of the co-authors are employees of Bayer.
Primary source: American Society of HematologySource reference:Eriksson BI, et al "Oral rivaroxaban compared with subcutaneous enoxaparin for extended thromboprophylaxis after total hip arthroplasty: the RECORD1 Trial" Blood 2007; 110(1 pt 2): 9a. Abstract 6.