Dabigatran Etexilate: A New Oral Thrombin Inhibitor

Abstract

Long-term oral anticoagulation is indicated for several cardiovascular diseases, including the prevention of cardiac thromboembolism in patients with atrial fibrillation (AF),1 mechanical heart valves,2 and acute myocardial infarction (MI),3 as well as the secondary prevention of venous thromboembolism (VTE).4

For the past 60 years, oral vitamin K antagonists (eg, warfarin, acenocoumarol, phenprocoumon, fluindione) have been widely prescribed.5 However, their impact in preventing thromboembolism has been hampered by several limitations that compromise their effectiveness and safety and make them difficult to use (Table 1). Vitamin K antagonists have a delayed onset and offset of action that often prolong hospitalization, and thus increase healthcare costs. Their large interindividual variability in dose response and narrow therapeutic window demand regular monitoring of the international normalized ratio (INR) and result in complex individualized dosing. Despite careful dose adjustment, the INR is frequently outside the target therapeutic range, which increases the risk of thromboembolism and bleeding.6 Patients treated with a vitamin K antagonist require counseling about drug and food interactions, the need for routine monitoring, and the inherent risk of bleeding. To reduce some of the dose variability, an algorithm based on clinical and genetic data has been developed and validated for estimating the appropriate dose of warfarin,7 but evidence of the cost-effectiveness of pharmacogenetic testing to optimize warfarin dosing in routine clinical practice is lacking.8

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Citation
Circulation 2011;123:1436-50