Dabigatran - the First Approved DTI for SPAF

Abstract

Atrial fibrillation (AF) is commonly occurring arrhythmia in clinical practice. AF is easy to recognize but difficult to treat. Stroke is the most devastating complication of AF and is associated with a huge disease burden on the society. Effective stroke prevention is a priority for patients with AF. Two-thirds of strokes due to AF are preventable with suitable anticoagulant therapy. VKA like warfarin, acenocoumarol remains the gold standard for stroke prevention in AF (SPAF). However, it is associated with numerous limitations such as a high risk of drug-drug, drug-food interactions and need for frequent PT/INR monitoring. Dabigatran etexilate is a selective, specific, reversible direct thrombin inhibitor that has been approved in United States, European countries and in India for SPAF and primary venous thromboembolism prevention and treatment. The efficacy and safety of dabigatran in AF has been established the "Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY)", a randomized clinical trial. As per RE-LY trial 150-mg dose of dabigatran was superior to warfarin with respect to stroke or systemic embolism, and the 110-mg dose was superior to warfarin with respect to major bleeding. The adverse event profile of dabigatran etexilate was generally similar to that of warfarin in the RE-LY study, except for the incidence of dyspepsia. Dabigatran has edge over VKAs like warfarin and acenocoumarol including predictable pharmacokinetic and pharmacodynamic profile, minimal drug-drug and no drug-food interactions while no monitoring is needed. Dosing schedule is dabigatran 150mg BID patients with normal renal function. 110 mg BID is specifically for elderly patients above 80 years and over, as well as for patients at an increased risk of bleeding and in renal impairment CrCL 15-30 mL/min dosing is 75mg twice daily. Dabigatran is only NOAC with approved specific reversal agent.