The focus of this review is the evolving field of antithrombotic drug therapy 
for stroke prevention in patients with atrial fibrillation (AF). The current 
standard of therapy includes warfarin, acenocoumarol and phenprocoumon which 
have proven efficacy by reducing stroke by 68% against placebo. However, a 
narrow therapeutic index, wide variation in metabolism, and numerous food and 
drug interactions have limited their clinical application to only 50% of the 
indicated population. Newer agents such as direct thrombin inhibitors, factor Xa 
inhibitors, factor IX inhibitors, tissue factor inhibitors and a novel vitamin K 
antagonist are being developed to overcome the limitations of current agents. 
The direct thrombin inhibitor dabigatran is farthest along in development. 
Further clinical trial testing, and eventual incorporation into clinical 
practice will depend on safety, efficacy and cost. Development of a novel 
vitamin K antagonist with better INR control will challenge the newer 
mechanistic agents in their quest to replace the existing vitamin K antagonists. 
Till then, the large unfilled gap to replace conventional agents remains open. 
This review will assess all these agents, and compare their mechanism of action, 
stage of development and pharmacologic profile.