EINSTEIN-Extension, which will be presented as a late-breaking clinical trial at the American Society of Hematology meeting in New Orleans on December 8, demonstrates that rivaroxaban (Xarelto), the direct oral factor Xa inhibitor, is effective in the long-term prevention of recurrent venous thromboembolism. But a high bleeding rate may dampen enthusiasm for the new oral anticoagulant.

The trial randomized 1,197 patients who had already completed 6-12 months of anticoagulant treatment for a first acute episode of VTE to either rivaroxaban or placebo for an additional 6-12 months. Symptomatic recurrent VTE occurred in  42 (7.1%) of placebo patients and 8 (1.3%) of rivaroxaban patients, representing a highly significant 82% relative risk reduction. When therapy was stopped, after a mean duration of 190 days, there were 6 new events in each group in the following month.

There were no major bleeds in the placebo group compared to 4 (0.7%) in the rivaroxaban group. Non-major bleeds occurred in 7 placebo patients and 32 rivaroxaban patients.

Wells Fargo analyst Larry Biegelsen wrote that “enthusiasm for Xarelto has declined among key opinion leaders” in the wake of the highly promising results for dabigatran (Pradaxa) in the RE-LY trial presented at the ESC. The bleeding rate in EINSTEIN-Extension suggests that rivaroxaban may not outperform warfarin in the ROCKET-AF trial, which is comparing rivaroxaban to warfarin for the prevention of stroke in AF. (Previous trials with warfarin suggest that warfarin may have a lower annual bleeding than rivaroxaban in this setting.)

Click here to see previous CardioBrief coverage of rivaroxaban.

Click here to read the EINSTEIN-Extension abstract from ASH.

Here is the press release from Johnson & Johnson:

Positive Results from Chronic Study with Bayer ’s Rivaroxaban Will be Presented As a Late Breaker at ASH 2009

Positive Results from Chronic Study with Bayer’s Rivaroxaban Will be Presented As a Late Breaker at ASH 2009 Endpoints met in EINSTEIN-Extension Trial in the Secondary Prevention of Recurrent Symptomatic VTE

Berlin, November 19, 2009 – Findings from the Phase III EINSTEIN-Extension study will be presented in the Late Breaking Abstract Session on December 8, 2009, (7:30 am EST, Hall F, Ernest N. Morial Convention Center) at the 51st Annual Meeting of the American Society of Hematology (ASH) in New Orleans, Louisiana.

The study investigated the long-term benefits of 20 mg rivaroxaban once-daily compared with placebo in the secondary prevention of recurrent symptomatic venous blood clots in approximately 1,200 patients with symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE). These patients had already completed 6 or 12 months of anticoagulant therapy, either as part of their routine care for an acute episode of venous thromboembolism (VTE) or as a participant in the EINSTEIN-DVT or EINSTEIN-PE clinical trials, where patients received either rivaroxaban or a vitamin K antagonist.

The abstract (lba-2) is available online at the ASH website: http://www.hematology.org/Meetings/Annual-meeting/.

About EINSTEIN EINSTEIN is a global clinical development program of three trials in approximately 8,000 patients. Two of these studies enrolled patients with acute, symptomatic deep vein thrombosis (EINSTEIN-DVT, enrollment complete) or pulmonary embolism (EINSTEIN-PE). In these two programs, patients received oral rivaroxaban 15 mg twice-daily for three weeks, followed by oral rivaroxaban 20 mg once-daily, compared with initial enoxaparin treatment followed by a vitamin K antagonist. The third study, EINSTEIN-Extension, was designed to evaluate the long-term benefits of rivaroxaban treatment in the secondary prevention of recurrent symptomatic VTE versus placebo.

New Findings Reinforce Landmark Results from RECORD Program Rivaroxaban, a novel oral, direct Factor Xa inhibitor, consistently demonstrated superior efficacy over enoxaparin, whilst maintaining a similar safety profile, in the Phase III RECORD clinical trial program. The aim of the RECORD program was to evaluate rivaroxaban in the prevention of VTE following elective total hip or knee replacement surgery. Results of the RECORD1, 2 and 3 trials were presented at ASH in 2007.

About rivaroxaban Rivaroxaban was invented in Bayer’s Wuppertal laboratories in Germany, and is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Rivaroxaban is marketed under the brand name Xarelto®, and approvals have been granted for the prevention of VTE in adult patients undergoing elective hip or knee replacement surgery in over 80 countries, including the EU, Australia, Canada, China and Mexico. To date, Xarelto® has been launched in more than 50 countries around the world by Bayer HealthCare.

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, which will evaluate the product in the prevention and treatment of a broad range of acute and chronic blood-clotting disorders, including VTE treatment, stroke prevention in patients with atrial fibrillation, secondary prevention of acute coronary syndrome, and VTE prevention in hospitalized, medically ill patients.

To learn more about thrombosis, please visit http://www.thrombosisadviser.com

About Bayer HealthCare The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Bayer Schering Pharma, Consumer Care and Medical Care divisions. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. Find more information at http://www.bayerhealthcare.com.

About Bayer Schering Pharma Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company. Its research and business activities are focused on the following areas: Diagnostic Imaging, General Medicine, Specialty Medicine and Women’s Healthcare. With innovative products, Bayer Schering Pharma aims for leading positions in specialized markets worldwide. Using new ideas, Bayer Schering Pharma aims to make a contribution to medical progress and strives to improve the quality of life. Find more information at http://www.bayerscheringpharma.de.

Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at http://www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.