The Lancet Neurology published positive results from a sub-group analysis of the landmark Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial - the largest atrial fibrillation (AF) outcomes trial ever completed (18,113 patients in 44 countries worldwide). The new findings fully support the convincing results from the RE-LY trial and show that AF patients with previous stroke or transient ischemic attack (TIA) may benefit substantially from treatment with dabigatran etexilate.

The new sub-group analysis from RE-LY included 3,623 AF patients who had suffered a stroke or TIA before enrolment into the trial. The results of the sub-group analysis were consistent with the overall trial results for the major efficacy and safety outcomes. This was confirmed by an interaction analysis which showed that results in patients with previous stroke or TIA were consistent with the overall results found in the RE-LY trial.

The 150 mg dose of dabigatran etexilate provided a substantial 25 per cent reduction in relative risk compared with well controlled warfarin in the combined endpoint of stroke and systemic embolism in the sub-group of patients with previous stroke or TIA in line with the results of the main RE-LY trial. However, due to the five fold smaller sample size of this subpopulation compared to RE-LY, this difference did not reach statistical significance. Impressively, both doses (110 mg BID and 150 mg BID) also demonstrated significant reductions in intracranial bleeds versus well controlled warfarin. These findings support the overall striking results of RE-LY in the prevention of stroke and systemic embolism of dabigatran etexilate, within a patient sub-group who are at 2.5 times increased risk compared with a typical AF patient without previous stroke or TIA, who themselves are already at 5-times increased risk.

Based on the convincing results of RE-LY, dabigatran etexilate was approved in the USA for stroke risk reduction in patients with non-valvular AF and in Canada for the prevention of stroke and systemic embolism in patients with AF for whom anticoagulation is appropriate.

New data from the RE-LY trial and dabigatran etexilate will be available at this year’s American Heart Association Scientific Sessions 2010, Chicago, US, 13-17 November.

RE-LY (Randomized Evaluation of Long term anticoagulant therapY) was a global, phase III, randomised trial of 18,113 patients enrolled in over 900 centres in 44 countries, investigating whether dabigatran etexilate (2 blinded doses) is as effective as well controlled warfarin with target INR of 2.0-3.0 for stroke prevention. Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.

The primary endpoint of the trial was incidence of stroke (including haemorrhagic) or systemic embolism. Secondary outcome measures included all-cause death, incidence of stroke (including haemorrhagic), systemic embolism, pulmonary embolism, acute myocardial infarction, and vascular death (including death from bleeding).

Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs) 18 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 in 75 countries under the trademark Pradaxa (in Canada: Pradax) for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery.