Impressive data from three trials have been published which once again demonstrate the superiority of Bayer/Johnson & Johnson’s new oral anticoagulant rivaroxaban over Sanofi-Aventis’ Lovenox.
First of all, The Lancet published data from the RECORD 2 study which demonstrates that extended rivaroxaban treatment was significantly more effective at reducing the number of venous blood clots in patients undergoing total hip replacement surgery compared with short duration Lovenox (enoxaparin) followed by placebo. The study showed a 79% relative risk reduction in total VTE with five weeks of treatment with rivaroxaban (10mg tablet once-daily) compared to two weeks of subcutaneous enoxaparin (40mg injection once-daily). Also, the five-week rivaroxaban regimen showed a similar low rate of bleeding when compared to two weeks on Lovenox.
After that, RECORD 1 and RECORD 3 studies were published in the New England Journal of Medicine which demonstrated that oral rivaroxaban, which Bayer plans to market as Xarelto, once daily, is significantly more effective than Lovenox in preventing venous blood clots in total hip and knee replacement surgery patients, with comparably low bleeding rates between the treatment arms.
RECORD 1 data showed a 70% relative risk reduction in total VTE from 3.7% in those administered enoxaparin to 1.1% for those on rivaroxaban in patients undergoing total hip replacement surgery. RECORD 3 data revealed a 49% RRR in total VTE from 18.9% in those administered enoxaparin to 9.6% for those on rivaroxaban in patients undergoing total knee replacement surgery.
All three trials have been presented previously and the their publication comes on the back of data from RECORD 4 earlier this month. That was the first trial to evaluate Xarelto against enoxaparin 30mg injected subcutaneously twice-daily.
In the Lancet editorial, Drs John Eikelboom and Jeffrey Weitz of the McMaster University in Ontario note that for over 60 years, vitamin-K antagonists such as warfarin have been the only available oral anticoagulants, and although effective, these drugs are “challenging to use”. Unpredictable anticoagulant responses necessitate monitoring and frequent dose adjustments, which is inconvenient for patients, and costly too.
However, rivaroxaban is orally active and produces “such a predictable anticoagulant response that no monitoring is required”. Eikelboom and Weitz say that following the four Phase III RECORD trials, “with superior efficacy, no compromise in safety, and a convenient once-daily regimen, rivaroxaban seems an obvious choice for simplified thromboprophylaxis after hip or knee arthroplasty,”
Xarelto has been filed in Europe for the prevention of VTE after major orthopaedic surgery of the lower limbs but fellow German firm Boehringer Ingelheim has already received marketing authorisation from the European Commission for its blood clot drug Pradaxa (dabigatran etexilate) thus stealing a march on Bayer’s treatment.
