A new landmark study, called RE-COVER?, a global, phase III, randomized, double blind, parallel-group study evaluating whether oral dabigatran etexilate (Pradaxa?, Boehringer Ingelheim; 150 mg BID), is as effective and safe as (non-inferior to) warfarin (INR 2.0-3.0) for 6 months treatment of acute symptomatic venous thromboembolism, following initial treatment (5-11 days) with a parenteral anticoagulant, provides welcome news for patients with a common clotting disorder known as venous thromboembolism (VTE).According to the Venous Disease Coalition, 1 million Americans experience VTE every year, which occurs when an abnormal clot forms in a vein and restricts the flow of blood, causing pain and swelling. In some cases, the clot may detach from its point of origin and travel through the heart to the lungs, causing a potentially fatal condition known as a pulmonary embolism.Currently, patients with VTE are treated with a blood thinner known as warfarin, which has many burdensome interactions with other medications and foods and requires frequent monitoring of the dosage. However, this study shows that a new oral direct thrombin inhibitor drug called dabigatran etexilate, which does not have these disadvantages, is as safe and effective as warfarin for combating VTE.To compare the two drugs, an international team of researchers conducted a randomized, double-blind trial of 2,539 patients with acute VTE. For six months, roughly half of the patients in the trial (1,274) were given a fixed dose of 150 mg of dabigatran etexilate twice daily, while the other half (1,265 patients) were given warfarin once daily in doses adjusted to an International Normalized Ratio (INR) of 2.0 to 3.0. INR is a blood test needed to monitor the effects of warfarin therapy to ensure an adequate, yet safe, dose is taken; in this study, the test was performed, on average, every 11 days.The improvement seen in both groups from the treatments was similar. After six months of treatment, only 2.4% of the dabigatran etexilate group (30 patients) and 2.2% of the warfarin group (27 patients) experienced recurrent VTE. The safety of the two drugs was also comparable. In the dabigatran etexilate arm, 207 patients experienced bleeding (including 20 patients with major bleeding) versus 280 patients in the warfarin arm (including 24 with major bleeding). Other possible side effects, including death, acute coronary syndromes, and abnormalities in liver function tests, were infrequent in the two groups.?The results of the RE-COVER? trial are very encouraging news for VTE patients.? said Eve Knight, Chief Executive of the patient organisation AntiCoagulation Europe. ?Although warfarin is an effective treatment it imposes many restrictions on patients? lives as they require regular blood tests, dose adjustments and have limitations placed on the food and drink they can consume. In addition, the unpredictability of warfarin places patients at risk of recurrent clots or increased bleeding if it is not sufficiently monitored. AntiCoagulation Europe therefore welcomes the news that dabigatran may offer a safer, more simple alternative to warfarin for the treatment of potentially life-threatening blood clots.?Current guidelines recommend treating acute VTE with anticoagulants to prevent new blood clots from forming and old ones from getting any bigger, as well as reducing the risk of both post thrombotic syndrome and thromboembolic pulmonary hypertension. These chronic diseases can cause substantial illness and a high economic burden. Current standard treatment involves the short-term use of a low molecular weight heparin for therapy initiation in hospital with subsequent continuation of treatment with a vitamin K antagonist (VKA, such as warfarin). 8 This provides a three-fold reduction in recurrence of VTE and extended duration of therapy reduces this risk by 50%.While VKAs are highly effective anticoagulants, they have multiple limitations which make maintaining patients within the narrow therapeutic INR range of 2.0-3.0 challenging, requiring frequent monitoring to ensure patient safety and efficacy. Even with close monitoring, as in a clinical trial, patients only spend half their time within this range and this tends to be even lower in the ?real-world setting?. 11 Outside of the narrow range, the rate of bleeding is 44% and the rate of clotting is 48%.?We are excited by these findings and feel that they will change the standard of care for venous thromboembolism, which affects a large number of our patients,? said lead study author Sam Schulman, MD, Professor of Medicine, Thrombosis Service, McMaster Clinic and Hamilton General Hospital in Ontario, Canada. ?This study found that dabigatran is a safe and effective anticoagulant that does not require the routine monitoring or dose adjustments that are necessary with warfarin. In other words, patients can receive the same results in a more convenient manner.?Dr. Schulman will present the results of this study (Dabigatran Etexilate Versus Warfarin in the Treatment of Venous Thromboembolism; Abstract #1) during the Plenary Scientific Session of the 51st Annual Meeting of the American Society of Hematology (New Orleans, December 5 – 8, 2009) on Sunday, December 6, at 2:00 p.m. in Hall F.
