Update on Pharmacologic Approaches to Prevent Thromboembolism in Atrial Fibrillation: Are Thrombin and Factor Xa Inhibitors the Ultimate Answer?

Oliver      Wolfram; Matthias      Hammwoehner; Felix      Gramley; Andreas      Goette

doi:10.2174/157016111795495512

Abstract

Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia. Prevalence and incidence rates are rising with the advancing population age. A severe complication of untreated AF is thrombus formation in the left atrial appendage with consecutive peripheral thromboembolism. Thus, AF is a major contributor to thromboembolic events, especially in the elderly. Depending on the CHADS2 score for thromboembolic events that takes into account congestive heart failure, hypertension, age, diabetes mellitus and stroke as risk factors, oral anticoagulation therapy with vitamin K antagonists is currently the treatment of choice for the prevention of thromboembolism. However, due to drawbacks of current anticoagulation therapy new substances for oral therapy are currently evaluated in various clinical studies. This article provides an up to date overview of orally active compounds for the future treatment of AF. Emphasis lies on comparison of direct thrombin inhibitors with factor Xa inhibitors that are currently investigated in clinical phase III studies for the treatment of non-valvular AF. The direct thrombin inhibitor dabigatran will be compared with factor Xa inhibitors like rivaroxaban and apixaban. Other promising agents currently investigated in phase II trials such as direct factor Xa inhibitors DU-176b (edoxaban) and YM150, will also be discussed.

Keywords: Atrial fibrillation, anticoagulation, pathophysiology, pharmacology, stroke, thromboembolism, congestive heart failure, hypertension, diabetes mellitus, thrombin inhibitors, thrombin, factor Xa Inhibitors