Boehringer Ingelheim announced that the last patient has completed treatment in the landmark phase-III Randomized Evaluation of Long term Anticoagulant therapy (RE-LY) study. This study compares the long-term efficacy and safety of the novel, oral direct thrombin inhibitor dabigatran etexilate (Pradaxa) with the current standard therapy, warfarin (target international normalized ratio, INR, 2-3) for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF).
Pradaxa is the most advanced oral anticoagulant in development in this therapeutic area. RE-LY, the largest stroke prevention in AF trial to date, enrolled 18,113 patients, in over 900 centres in 44 countries worldwide between December 2005 and December 2007. Data will now be analysed and results are expected to be presented later this year at the European Society of Cardiology (ESC) Congress, taking place in Barcelona, Spain, from August 29th until September 2nd 2009.
"We are proud to announce completion of treatment of the last patient in the RE-LY study, which is addressing a key area of unmet clinical need, and would like to thank patients and investigators involved," commented Dr Manfred Haehl, corporate senior vice president Medicine, Boehringer Ingelheim, "This marks another milestone in our extensive Re-Volution programme involving over 38,000 patients evaluating our novel oral direct thrombin inhibitor dabigatran etexilate in a range of thromboembolic conditions."
AF is the most common heart rhythm condition, affecting 1 per cent of the total population and 10 per cent of those over 80 years, with prevalence expected to rise due to the ageing society. In 2007, 6.3 million people in the US, Japan, Germany, Italy, France, UK and Spain were living with diagnosed AF. People with AF are at an increased risk of blood clots, raising their risk of stroke by up to seven times. Two out of three strokes due to AF can be prevented with appropriate anticoagulant therapy. Vitamin K antagonists (warfarin, coumarins) are the current standard therapy and are highly effective when patients are maintained within the therapeutic INR range of 2.0-3.0 for the majority (60-70 per cent) of time. Due to the limitations associated with vitamin K antagonists, such as numerous drug-drug/drug-food interactions and a slow onset of effect, maintaining patients within this narrow therapeutic range is difficult for clinicians and requires frequent monitoring of the drug's effects to ensure optimal patient safety. A retrospective review demonstrated that patients in routine clinical practice only spend approximately half of the time in the therapeutic INR range.
Moreover, it is estimated that approximately 50 per cent of patients diagnosed with AF and at risk of stroke, who are eligible for warfarin therapy according to guidelines, do not receive anticoagulant treatment. A key reason is the limitations associated with warfarin which make it unsuitable for many patients, however there is no effective alternative therapeutic option for this group. Thus, applying guideline therapeutic recommendations to real-world practice is challenging for physicians and patients. There is a need for an effective and safe new oral anticoagulant without the limitations of vitamin K antagonists. Pradaxa provides predictable, 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.
RE-LY is investigating whether the novel oral direct thrombin inhibitor dabigatran etexilate (2 blinded doses) is as effective as well controlled warfarin (open label) for stroke prevention in patients with non-valvular AF and at least one other major risk factor for stroke (i.e., previous ischaemic stroke, transient ischaemic attack, systemic embolism, left ventricular dysfunction, age =/>75 years, age =/>65 with either diabetes mellitus, history of coronary artery disease, or hypertension). Patients have been followed for a minimum of one year.
The primary outcome of the trial is incidence of stroke (including haemorrhagic) and systemic embolism. Secondary outcome measures include all death, incidence of stroke (including haemorrhagic), systemic embolism, pulmonary embolism, acute myocardial infarction and vascular death (including death from bleeding). Additional safety endpoints include major and minor bleeding events, intracerebral haemorrhage, elevations in liver transaminases, bilirubin and hepatic dysfunction.
Pradaxa - a direct reversible thrombin inhibitor - is at the forefront of a new generation of oral anticoagulants targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.
RE-LY is part of Boehringer Ingelheim's extensive Re-Volution clinical trial program - evaluating the efficacy and safety of dabigatran etexilate against current standard therapy in over 38,000 patients.