Data Presented at ISTH Reinforces Positive Benefit-Risk Profile of Xarelto®
Geschreven op 16.07.2009July 16, 2009 - The clinical value that Xarelto® (rivaroxaban),
a once-daily oral, direct Factor Xa inhibitor, brings to the field of anticoagulation medicine was reinforced by efficacy and safety data presented at the XXII Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Boston. The data add to the evidence that Xarelto is an effective treatment option for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective total hip (THR) or knee replacement surgery (TKR) surgery.1,2, 3 Xarelto has been approved in more than 50 countries worldwide since the first approval was granted in September 2008.
"The depth and breadth of the data presented at ISTH highlight the benefits that Xarelto brings to patients, doctors and healthcare providers," said Frank Misselwitz, MD, Vice President of Global Clinical Development and Head of the Therapeutic Area Cardiovascular and Coagulation, Bayer Schering Pharma AG. "These clinical findings confirm the benefits that Xarelto delivers in VTE prevention after THR and TKR and its good tolerability profile."
Xarelto significantly reduces symptomatic VTE and death
A pooled analysis of the four Phase III trials comprising the RECORD program, comparing Xarelto with enoxaparin for VTE prevention after THR and TKR, showed that age, weight, gender and renal function have no clinically relevant effect on Xarelto efficacy or safety, underlining the value it brings to patients.1 The RECORD trial program investigated 12,729 patients randomized to receive Xarelto (10mg tablet once daily) starting 6-8 hours after surgery, or enoxaparin (40mg) starting the evening before surgery, or enoxaparin (30mg twice daily) starting 12-14 hours after surgery.1 The pooled analysis showed that Xarelto was superior to enoxaparin in reducing symptomatic VTE and death in a number of key subgroups of the RECORD study population, with a similar safety profile, including a low rate of major bleeding.1
"In the RECORD program Xarelto was found to be effective across a wide range of patients having elective hip or knee replacement surgery," said Dr. A.G.G. Turpie, Principal Investigator in the RECORD program, Professor of Medicine, McMaster University, Canada. "It is the first of the new oral anticoagulants to show superiority over both the EU and US dosing of enoxaparin and it has the potential to become a new clinical standard for preventing blood clots after major orthopedic surgery."
Improved benefit-risk profile to current standard of care
One poster presented at ISTH investigated the potential impact of Xarelto on long-term safety outcomes after THR or TKR surgery based on the pooled analysis of all four RECORD studies. It showed that the overall incidence of adverse events (AEs) including post-procedural infection, postoperative wound infection and incision-site hemorrhage was low and similar between the groups, 1.83 percent for Xarelto vs. 2.11 percent for enoxaparin.2 The incidence of serious surgical AEs was also low and similar between the groups, 0.49 percent vs. 0.56 percent, respectively.2
Another poster presented, based also on the pooled analysis of RECORD 1-4, investigated bleeding events in thromboprohylaxis - an area of great importance to surgeons - and showed no significant differences in the risk of clinically relevant bleeding events between Xarelto and enoxaparin regimes in the early postoperative period, regardless of the type of surgery.3
Major bleeding, clinically relevant non-major bleeding (CRNM) and the composite of major plus CRNM bleeding were evaluated in the safety population of 12,383 patients up to day 12±2 (head-to-head comparison of Xarelto vs. enoxaparin in all four studies) and separately in the patients undergoing THR (6,890) and TKR (5,493). In the safety population the incidence of all bleeding endpoints was low and not significantly different between the Xarelto and enoxaparin groups. Xarelto demonstrated a favorable efficacy-safety ratio.3
However, results for the composite endpoint of major and clinically relevant non-major bleeding were also low but statistically significantly different for the total treatment duration time period [12±2 days following TKR and 35±4 days following THR, including extended (5 weeks) Xarelto treatment in RECORD2 compared to short-term (2 weeks) enoxaparin, followed by placebo for 3 weeks] with 3.2 percent for Xarelto vs. 2.5 percent for enoxaparin (p=0.039).3
About Venous Thromboembolism (VTE)
Blood clots can break apart and travel through the bloodstream, blocking blood flow to vital organs. VTE includes DVT, a blood clot in a deep vein (usually in the leg), and PE, a blood clot in the lung, both of which are serious, life-threatening - but often preventable - conditions. Patients undergoing major orthopedic surgery are at high risk for VTE because during hip or knee replacement procedures, the large veins of the leg that carry blood back to the heart can be damaged, significantly increasing the risk of developing a clot. In fact, venous blood clots occur in 40 to 60 percent of patients undergoing major orthopedic surgery who do not receive preventive care.
In the five largest EU-member states, approximately 450,000 total hip - and approximately 300,000 total knee replacement surgeries are being conducted annually.
About the RECORD Clinical Trial Program
The RECORD program comprised four Phase III trials (RECORD1, 2, 3 & 4) which involved more than 12,500 total hip or knee replacement surgery patients. Xarelto demonstrated superior efficacy over enoxaparin in all four RECORD trials, including head-to-head comparisons (RECORD1, 3 and 4), and a comparison of extended-duration (5 weeks) Xarelto with short-duration (2 weeks) of enoxaparin (RECORD2). RECORD4 evaluated Xarelto against enoxaparin 30 mg injected subcutaneously twice-daily, which is a U.S.-approved treatment regimen for enoxaparin. In all four trials, Xarelto and enoxaparin had similar safety profiles, including low rates of major bleeding.4,5,6,7
About Xarelto®
Xarelto was invented in Bayer's laboratories in Wuppertal, Germany, and is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Rivaroxaban is approved in the European Union for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery. Additional approvals have been granted in other countries, including Australia, Canada, China, Mexico and Singapore. To date, Xarelto has been launched in more than 30 countries around the world by Bayer Schering Pharma.
The extensive clinical trial program supporting rivaroxaban makes it the most studied oral, direct Factor Xa inhibitor in the world today. More than 65,000 patients are expected to be enrolled into the rivaroxaban clinical development program.
To learn more about thrombosis, please visit www.thrombosisadviser.com.
« Terug naar overzicht