Atrial fibrillation is the most common sustained
cardiac arrhythmia and the most frequently encountered cause of
embolic stroke.
Vitamin K antagonists (such as
warfarin) have represented the cornerstone of anticoagulation practice for the last 60 years. Although highly effective in preventing thromboembolic events among patients with
atrial fibrillation,
warfarin therapy is limited by a multitude of potential problems. Hence,
warfarin is significantly underused in clinical practice, with only half of
warfarin-treated patients actually achieving therapeutic anticoagulation in routine clinical practice. Consequently, there is an overwhelming need for an alternative oral
anticoagulant for patients with
atrial fibrillation that is safer, more practical and effective.
Ximelagatran (
Exanta, AstraZeneca) is a novel oral
direct thrombin inhibitor that is rapidly converted to the active compound
melagatran after oral absorption. It has a low potential for drug interactions, anticoagulation monitoring is not required, and it is administered at a fixed twice-daily dose. The
Stroke Prevention using the ORal
Thrombin Inhibitor in patients with nonvalvular
atrial Fibrillation (SPORTIF) III and V trials have together demonstrated the noninferiority of
ximelagatran relative to
warfarin for the prevention of
stroke and embolic events in
atrial fibrillation. Unfortunately, initial optimism has been tempered by serious concerns over its safety data in view of its propensity to cause elevation in liver
enzymes.