Review of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Trial: Warfarin Versus Dabigatran

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Introduction: Atrial fibrillation is the most common sustained arrhythmia in clinical medicine affecting over 2 million Americans. As the population ages, the risk of atrial fibrillation increases with a prevalence of 9%, and a yearly incidence of 2% in octogenarians [1–3]. Atrial fibrillation is an independent risk factor for stroke, with a yearly rate of ischemic stroke of approximately 5% [3, 4]. Patients with atrial fibrillation have an increased mortality compared with matched controls [3, 5]. Warfarin has been the recommended antithrombotic for prevention of strokes in patients with atrial fibrillation and at least one risk factor for ischemic stroke [6]. Warfarin is more effective than placebo in decreasing stroke risk, with a relative risk reduction in ischemic stroke of 64% [7]. Antiplatelet agents when compared with placebo only decrease the risk of stroke by 22% [7]. In addition, warfarin is more effective than antiplatelet agents, with a 39% relative risk reduction in ischemic stroke [7, 8]. However, warfarin has many potential drawbacks, making it difficult to implement in clinical practice. Factors such as drug and dietary interactions, delayed onset and offset of action, cumbersome International Normalized Ratio (INR) monitoring, elevated risk of bleeding, and difficulties maintaining a therapeutic INR all contribute to limiting the number of patients prescribed warfarin, as well as decreasing the time in the therapeutic window for patients on warfarin therapy. Given the large and growing population with and at risk for atrial fibrillation as well as the difficulties encountered in utilizing warfarin for stroke prevention, new antithrombotic medications have been developed. One of the first class of medications to undergo clinical testing has been the direct thrombin inhibitors. Dabigatran etexilate (Boehringer Ingelheim Pharmaceuticals, Biberach, Germany) has recently been tested in a large clinical trial (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy]). Dabigatran etexilate is an orally administered competitive and reversible direct thrombin inhibitor. It is a prodrug that is metabolized to its active form by plasma and hepatic esterases. It is not metabolized by the P450 system, has a 6.5% bioavailability, and is predominately renally excreted. Dabigatran does not require periodic monitoring and there is no widespread available test to determine the magnitude of anticoagulation [9–11].