Dabigatran etexilate as effective and safe as enoxaparin in preventing venous thromboembolism (VTE) after total hip replacement surgery and significantly reduced the combined endpoint of major VTE and VTE-related death

• Dabigatran etexilate 220mg once daily is as effective and safe as enoxaparin 40mg in preventing venous thromboembolism (VTE) after total hip replacement surgery ¹
• Compared to enoxaparin, dabigatran etexilate significantly reduced the combined endpoint of major VTE and VTE-related death ¹
• Dabigatran etexilate is associated with a similar bleeding risk and safety profile compared to enoxaparin. ¹

Ingelheim, Germany, 11 June 2010. Data from the RE-NOVATE® II study presented today at the 15th Annual Congress of the European Hematology Association (EHA) have shown that dabigatran etexilate 220mg once daily is as effective and safe as enoxaparin 40mg in preventing venous thromboembolism (VTE) after total hip replacement surgery. The results also showed that dabigatran etexilate significantly reduced the combined endpoint of major VTE and VTE-related death compared to enoxaparin.¹

The double-blind non-inferiority trial randomized 2,055 patients and was designed to investigate whether treatment with dabigatran etexilate 220mg once daily was as effective as enoxaparin over 28-35 days in patients undergoing total hip replacement surgery and to compare the safety profiles of the two treatments.¹

Currently, existing treatments such as heparins (like enoxaparin) require regular injections for the prevention of VTE following total hip replacement surgery. However, this can be inconvenient for patients outside of the hospital setting especially when extended prophylaxis is carried out, which significantly reduces the number of VTE events.² Oral anticoagulants such as dabigatran etexilate are therefore seen as a development in facilitating improved patient care.

In detail, the results showed:¹

• Dabigatran etexilate is as effective as enoxaparin in preventing total VTE (venographic or symptomatic) and death from all causes. The outcome occurred in 7.7% of patients taking dabigatran etexilate and 8.8% of patients taking enoxaparin (absolute risk difference -1.1% (95% CI, -3.8% to 1.6%); p<0.0001 for non-inferiority).
• Dabigatran etexilate significantly reduced the combined endpoint of major VTE (proximal deep-vein thrombosis, nonfatal pulmonary embolism) and VTE-related mortality compared with enoxaparin. The outcome occurred in 2.2% of patients taking dabigatran etexilate and 4.2% of patients taking enoxaparin (absolute risk difference -1.9%, relative risk reduction - 46% (95% CI -3.6% to -0.2%); p=0.03 for superiority).
• Major bleeding events* were comparable between both treatments with 1.4% of patients reported in the dabigatran etexilate group and 0.9% patients taking enoxaparin (p=0.40).

Michael Huo, MD, Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center said, "These positive findings, together with the results of RE-NOVATE®, a study of analogous design with the combined data of more than 5,000 patients, confirm that dabigatran etexilate once daily is as effective as enoxaparin in patients following total hip replacement surgery for the prevention of VTE, with a similar bleeding risk and safety profile. The additional and encouraging finding from this trial is that dabigatran etexilate was associated with significantly lower rates of major VTE and VTE-related mortality."

VTE, comprising deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a major public health problem in Europe with nearly 750,000 VTE events taking place each year and approximately 300,000 of these being fatal.³ Three out of five patients develop DVT after major orthopaedic surgery without anticoagulant treatment,⁴ with one in five patients undergoing total hip replacement surgery developing DVT despite five-11 days of anticoagulant treatment.⁴ New anticoagulants are therefore needed to improve patient care and aid the prevention of thromboembolic disease.

Michael Huo continued, "As dabigatran etexilate is administered orally, it is more convenient than injectable anticoagulants such as enoxaparin for patients outside of the hospital setting. This advantage can also provide cost-saving benefits for national healthcare systems, as shown in the United Kingdom where the extended use of dabigatran etexilate was shown to provide a significant reduction in costs due to its oral administration when compared with enoxaparin. Dabigatran etexilate should therefore be considered an attractive treatment option in this clinical setting."

Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs) targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.⁵ Dabigatran etexilate is currently being investigated in a number of other therapy areas including stroke prevention in atrial fibrillation.

About RE-NOVATE®:⁶
RE-NOVATE® was a multinational, randomised, double-blind, non-inferiority, phase III trial involving 3,494 patients undergoing total hip replacement surgery in the European Union, South Africa, and Australia. Patients were randomised to receive either oral dabigatran etexilate 150 mg or 220 mg once daily or enoxaparin 40 mg once daily by subcutaneous injection started 12 hours before surgery. The median treatment duration was 33 days for all treatment groups.

For the primary efficacy endpoint of total VTE and death from all-causes, results were similar between all groups, occurring in 8.6%, 6.0%, and 6.7% of patients assigned to 150 mg or 220 mg dabigatran etexilate once daily or 40 mg enoxaparin once daily, respectively. Safety was evaluated for 3,463 patients receiving study treatment and no significant difference in major bleeding rates was observed between the groups (1.3%, 2.0%, and 1.6% respectively). The incidence of liver enzyme elevations and acute coronary events during the treatment or during the follow-up period did not differ significantly between the groups.

About dabigatran etexilate (Pradaxa®)
Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs)5 targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.

Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin (both free and clot-bound), the central enzyme in the process responsible for clot (thrombus) formation. In contrast to vitamin-K antagonists, which variably act via different coagulation factors, dabigatran etexilate provides effective, predictable and consistent anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or dose adjustment.

Dabigatran etexilate has already been approved and is widely utilized in over 50 countries under the trademark Pradaxa® for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery.

About the dabigatran etexilate clinical trial program
Boehringer Ingelheim’s clinical trial program to evaluate the efficacy and safety of dabigatran etexilate encompasses studies in:

• Primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee replacement surgeries
• Treatment of acute VTE
• Secondary prevention of VTE
• Secondary prevention of cardiac events in patients with acute coronary syndrome (ACS)
• Stroke prevention in atrial fibrillation (AF).

Please be advised
This release is from the Corporate Headquarters of Boehringer Ingelheim and is intended for international markets. This being the case, please be aware that there may be some differences between countries regarding specific medical information including licensed uses. Please take account of this when referring to the material.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro while spending 21% of net sales in its largest business segment Prescription Medicines on research and development.