Treating abdominal and pelvic cancer surgery patients with Clexane/Lovenox (enoxaparin sodium) to prevent venous thromboembolism (VTE) for four weeks compared to one week reduces the incidence of thromboembolic complications by 60 percent without compromising safety, according to a study published in the March 28 issue of The New England Journal of Medicine.
"The dramatic reduction in thromboembolic events seen across a broad spectrum of patients in this study demonstrates that prolonged prophylaxis with enoxaparin should be considered for all patients undergoing surgery for abdominal cancers," said David Bergqvist, MD, PhD, Academic Hospital, Uppsala, Sweden, lead author of the study. "We now know that a prolonged course of enoxaparin is safe and effective in this patient population and can help minimize the serious risk of venous thromboembolism inherent in cancer surgery."
Cancer patients undergoing surgical procedures have at least twice the risk of postoperative deep-vein thrombosis (DVT) and more than three times the risk of fatal pulmonary embolism (PE) than non-cancer patients undergoing similar procedures. Approximately 1.2 million people were diagnosed with abdominal cancer in 2000, and surgery is frequently performed to treat these cancers. Low-molecular-weight heparins are often used to prevent VTE in surgical patients, and a one-week regimen of Clexane/Lovenox has been proven safe and effective in preventing VTE in patients undergoing surgery for abdominal cancers.
This prospective, placebo-controlled, double-blind randomized trial evaluated the safety and efficacy of thromboprophylaxis with Clexane/Lovenox for eight days vs. 28 days. In the study, 501 patients from 37 centers in Denmark, France, Greece, Israel, Italy, Sweden, Switzerland and the United Kingdom undergoing surgery for abdominal or pelvic cancer received 40 mg Clexane/Lovenox daily for eight days, beginning 10 to 14 hours before surgery. On day eight, patients were randomized and treated in the double-blind period with either continued Clexane/Lovenox prophylaxis or with placebo for an additional 20 days.
Bilateral venography (radiographic demonstration of a vein) was systematically performed on day 28 unless symptoms of VTE occurred earlier, in which case venography or other objective documentation of thromboembolism was required.
The primary efficacy endpoint was the incidence of post-operative DVT or PE on day 28. The primary safety endpoint was the incidence of hemorrhage during the double-blind period.
Of the 332 patients eligible for the efficacy analysis, 165 received Clexane/Lovenox during the double-blind period. There was a significant 60 percent reduction in VTE with one month vs. one week of Clexane/Lovenox, both at day 28 (12.0% vs. 4.8%, P=0.02) and at 3 months (13.8% vs. 5.5%, P=0.01). Three months after randomization, three patients in the Clexane/Lovenox group and six patients in the placebo group had died. There were no significant differences in the incidence of hemorrhage or other complications during either the double-blind or follow-up periods.
"The maintenance of a robust risk reduction even at three months indicates that the so-called 'rebound phenomenon,' in which a patient develops venous thromboembolism after discontinuing preventive treatment, may not be a factor when using enoxaparin," Dr. Bergqvist said.
Deep vein thrombosis (DVT) is the presence of a blood clot in a vein. Pulmonary embolism is a direct complication of DVT, in which a clot travels to and obstructs the arteries of the lung, often causing sudden death. Populations at risk include orthopedic and general surgery patents, trauma patients, patients with cancer, pregnant women, women who take birth control pills and people who have a genetic mutation that leads to hypercoagulation of the blood. DVT is difficult to diagnose and the risk of this condition remains hugely under-recognized. In the major world markets, approximately 730,000 people are diagnosed with deep vein thrombosis or pulmonary embolism every year.