New England Journal of Medicine Publishes Results from Two of the Landmark Phase III RECORD Studies with Rivaroxaban

Head-to-Head trials involving over 7000 patients after Major Orthopedic Surgery / Rivaroxaban superior to Enoxaparin in Preventing Venous Blood Clots / Bleeding rates were low and comparable between the treatment arms


Berlin, June 2008 – Data from two Phase III clinical trials published today in the New England Journal of Medicine (NEJM), demonstrated that the investigational anticoagulant rivaroxaban (Xarelto®), taken as one tablet daily, is significantly more effective than enoxaparin, a current standard of care, in preventing venous blood clots in total hip and knee replacement surgery patients. Bleeding rates in both studies were low and comparable between the two treatment arms.

NEJM has also published an accompanying editorial by Dr. Jens Lohrmann and Dr. Richard C. Becker entitled, “New Anticoagulants — The Path from Discovery to Clinical Practice“ which provides an additional independent perspective on these data and how they may impact thrombosis management.

Venous blood clots, also known as venous thromboembolism or VTE, are potentially deadly complications of major orthopedic surgery. Rivaroxaban is being jointly developed by Bayer HealthCare AG and Johnson & Johnson Pharmaceutical Research & Development, L.L.C..

“Today’s publications on rivaroxaban have the potential to change clinical practice in this field,” said Bengt Eriksson, M.D., Ph.D., Department of Orthopaedics, at the Sahlgrenska University Hospital, Sweden, Principal Investigator of the RECORD1 clinical trial. “The results demonstrate that we now seem to have an effective and safe oral anticoagulant for convenient prophylaxis of venous thromboembolism. This is of great importance since patients undergoing major surgery of the hip and knee are at high risk of developing such potentially life threatening complications and the risk of VTE extends beyond hospitalisation"

The first study, RECORD1 (REgulation of Coagulation in major Orthopedic surgery reducing the Risk of DVT and PE), showed that rivaroxaban, a direct Factor Xa inhibitor, provided patients undergoing total hip replacement surgery with a 70% relative risk reduction (RRR) in total VTE from 3.7% in those administered enoxaparin to 1.1% for those on rivaroxaban — without increasing bleeding rates. Top-line results from RECORD1 were first presented at the annual meeting of the American Society of Hematology (ASH) in December 2007.

The second study, RECORD3, showed that rivaroxaban provided patients undergoing total knee replacement surgery with a 49% RRR in total VTE from 18.9% in those administered enoxaparin to 9.6% for those on rivaroxaban — without increasing bleeding rates. Top-line results from RECORD3 were first presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in July 2007.

“The RECORD1 and RECORD3 study results show that rivaroxaban has the potential to set a new clinical standard in the treatment of blood clots and reduce the global burden of VTE” said Frank Misselwitz, M.D., PhD, Head of Cardiovascular Clinical Development, Bayer HealthCare AG. “The fact that rivaroxaban is significantly superior to enoxaparin in the prevention of VTE, with similar bleeding rates, not only offers patients relief from the inconveniences associated with today’s therapies, but also demonstrates that we may have found the right target along the complicated coagulation cascade.”

Current treatments such as vitamin K antagonists ( e.g., warfarin and acenocoumarol) and heparins have been the mainstays of anticoagulant treatment for many years; however, in the outpatient setting and for long-term use, each class has disadvantages. This has highlighted the need for new anticoagulants to be developed that are safe, effective and do not require regular injections or routine blood monitoring.

New Data to be Presented on June 27th at the International Congress on Thrombosis (ICT)
Five oral presentations and nine posters will be presented on rivaroxaban at the 20th ICT which is being held in Athens, Greece from 25 to 28 June 2008. Amongst the highlights will be the new and pre-specified pooled data-analysis of the RECORD1, 2 and 3 studies:
“A meta-analysis of three pivotal studies of rivaroxaban – a novel, oral, direct Factor Xa inhibitor – for thromboprophylaxis after orthopedic surgery” by Alexander Turpie, Michael Lassen, and Ajay Kakkar, et al., to be presented at 08:30–10:00 on Friday 27 June.

All of the accepted abstracts are to be published in a supplement of Pathophysiology of Haemostasis and Thrombosis.
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