Desirudin more effective for VTE prevention in patients with renal impairment

May 3 2011

Desirudin reduced major venous thromboembolism (VTE) and post-operative bleeding compared with the standard of care, enoxaparin, in patients with poor kidney function undergoing orthopedic surgery, according to a poster presented at the Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) meeting.

Entitled The Impact of Renal Function on Options for Venous Thromboembolism Prophylaxis Following Major Orthopedic Surgery: Insights from a Randomized Trial, the poster was presented at ATVB's annual meeting in Chicago on April 29. It was based on a retrospective analysis of the large, randomized trial that served as the pivotal trial in the approval by the Food and Drug Administration of desirudin.

"While we've long been concerned about the safety of anticoagulants in patients with poor kidney function, this is the first analysis to report a lack of efficacy with standard heparin therapy in this patient population," says Michael Kurz, PhD, one of the authors and Vice President, Global Medical Affairs of Canyon, desirudin's manufacturer. "Since this is post-hoc analysis, the findings will need to be investigated further in prospective trials, but our analysis addresses an important issue since nearly two-thirds of these patients had renal impairment."

The poster said: "VTE inversely correlated with GFR in enoxaparin-treated patients.

Desirudin provided consistent VTE prevention irrespective of renal function. There was no difference in major bleeding between groups. However, there appeared to be less post-operative bleeding in desirudin-treated patients with moderate renal impairment compared to enoxaparin-treated patients."

Desirudin is FDA-approved in the United States for the prevention of deep vein thrombosis (DVT) which may lead to pulmonary embolism (PE) in patients undergoing elective hip replacement surgery. It is available in the United States under the trade name Iprivask^®. Desirudin was the first direct thrombin inhibitor (DTI) approved for DVT prophylaxis in Europe, where it has been on the market for over 10 years under the trade name Revasc^®.

Study Design

The study that generated the data for the post-hoc analysis was a randomized, active-controlled, double-blind trial of desirudin 15 mg BID vs. enoxaparin 40 mg QD in patients undergoing elective total hip replacement surgery. Renal function was determined using the Cockcroft-Gault equation to calculate creatinine clearance (CrCl) and patients were stratified as having normal renal function (CrCl>60 ml/min) or renal impairment (CrCl≤60 ml/min). The primary efficacy endpoint was major VTE defined as the combination of proximal DVT, pulmonary embolism and unexplained death. The primary safety endpoint was post-operative major bleeding defined as a bleeding index of greater than two occurring more than 12 hours after surgery.

Results

Patients with renal impairment were more likely to be female (83 vs. 11%), older (70 vs. 60 years) and lighter weight (70 vs. 81 kg) than were patients with normal renal function. Patients with renal impairment randomized to desirudin had a 56% reduction in major VTE and a 45% reduction in major bleeding compared with patients randomized to enoxaparin.

"Desirudin appears to be a promising alternative anticoagulant for elderly women due to its attractive risk:benefit profile," said Dawn Bell, PharmD, Senior Vice President and General Manager of Canyon Pharmaceuticals.