Results from a pre-specified pooled analysis of the RECORD clinical trial programme confirmed that the novel oral anticoagulant Xarelto (rivaroxaban), taken as one tablet, once-daily, was superior to enoxaparin-based treatment regimens for the prevention of venous thromboembolism (VTE) after total knee or hip replacement surgery with low rates of major bleeding that were not statistically different from the comparator. Pooled results from the four RECORD trials, involving more than 12,500 patients, were presented at the 50th Annual Meeting of the American Society of Hematology (ASH) in San Francisco (USA). RECORD is the largest clinical trial programme ever conducted of an oral anticoagulant in the prevention of VTE after such surgeries.
"Swelling in the leg and shortness of breath are symptoms that can herald venous thromboembolism, which, in turn, can result in long-term complications or death," said Dr A G G Turpie, professor of Medicine, McMaster University, Canada, and Principal Investigator for the RECORD programme. "As a physician, one of my goals is to reduce patients' risk of complications, and these data show that Xarelto has the ability to reduce the composite of symptomatic VTE and all cause mortality by half when compared to enoxaparin."
The RECORD studies evaluated Xarelto (10 mg given as one tablet, once-daily) in the prevention of VTE following elective total knee replacement surgery (TKR) or total hip replacement surgery (THR) against enoxaparin at various doses and treatment durations. The pooled analysis had a primary composite efficacy endpoint of symptomatic VTE [symptomatic deep vein thrombosis (DVT) and symptomatic non-fatal pulmonary embolism (PE)] and all-cause mortality, which was analyzed at three different time points.
In one study, duration pool was day 42 post-TKR and day 65 post-THR, including a 30-day follow-up period after study drug discontinuation; the anther had total duration pool of 12±2 days following TKR and 35±4 days following THR, including five weeks rivaroxaban treatment in RECORD2 compared to two weeks enoxaparin treatment followed by placebo for three weeks; and the other had head-to-head treatment pool of 12±2 days post surgery.
At all three time points, patients treated with rivaroxaban demonstrated a statistically significant reduction of more than 50 per cent in the composite primary efficacy endpoint compared to patients treated with enoxaparin. Specifically, there was a 51 per cent relative risk reduction (RRR) in those treated with rivaroxaban vs. those treated with enoxaparin (0.8% vs. 1.6%, respectively, p<0.001) in the total study duration pool; a 58% RRR in the total treatment duration pool (0.6% vs. 1.3%, respectively, p<0.001) and a 52% RRR for those treated with rivaroxaban vs. those treated with enoxaparin (0.5% vs. 1.0%, respectively, p<0.001) in the head-to-head treatment pool.
These findings confirm the results of the four individual RECORD studies, which demonstrated the superior efficacy of Xarelto for preventing total VTE [composite of DVT, non-fatal PE, all-cause mortality], both in head-to-head comparisons with enoxaparin (RECORD1, 3 and 4) as well as when comparing extended-duration (5 weeks) Xarelto with short-duration (2 weeks) enoxaparin in RECORD2. In all four trials, Xarelto and enoxaparin had similar safety profiles.
"The combination of the efficacy and the safety profile of Xarelto may help change clinical practice to more accurately reflect established anticoagulation guidelines which are in place to protect patient lives," said Dr Turpie. "All the results reported from the RECORD programme strengthen my belief that direct Factor Xa inhibition with Xarelto has the potential to revolutionize the way we prevent the formation of dangerous blood clots."
Xarelto is approved for use in the European Union for the prevention of VTE in adult patients who have undergone elective total hip or knee replacement surgery.