Benefit-risk assessment of dabigatran in the treatment of stroke prevention in non-valvular atrial fibrillation.

Non-valvular atrial fibrillation (NVAF) is the most common clinically significant cardiac arrhythmia and is a common cause of stroke. The direct thrombin inhibitor dabigatran etexilate is approved for a variety of indications requiring anticoagulation, including stroke prevention in NVAF. Dabigatran does not require routine monitoring and exhibits only a few drug-drug interactions; however, impaired renal function needs observation. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study comprised about 18,000 patients with NVAF who received dabigatran 110 mg twice daily or 150 mg twice daily, or dose adjusted warfarin. Compared with warfarin, dabigatran 110 mg twice daily was associated with similar rates of stroke and systemic embolism, and lower rates of haemorrhage. Dabigatran 150 mg twice daily was associated with lower rates of stroke and systemic embolism but similar rates of haemorrhage. The rate of intracerebral haemorrhage (ICH) was significantly lower in both dabigatran arms. Basing on the results of the RE-LY study, the net clinical benefit balancing stroke against ICH has been estimated with various settings (study data, registry patients). In patients with low stroke risk but at high risk of bleeding, only dabigatran 110 mg twice daily had a positive net clinical benefit when compared with warfarin. In patients with higher stroke risks, both doses of dabigatran (110 and 150 mg twice daily) had a positive net clinical benefit even if the bleeding risk was high. Registry data after approval of dabigatran indicate similar stroke/systemic embolism and major bleeding rates with dabigatran (both doses) compared with warfarin. Pharmacovigilance sources prove the anticipated bleeding risk, but a refined analysis of such data showed that bleeding rates associated with dabigatran use did not appear to be higher than those associated with warfarin. Dabigatran confers an advantage over warfarin regarding stoke prevention without the burden of the surveillance of vitamin K antagonists, especially in patients with high stroke risk. However, in elderly patients with impaired renal function or considerable bleeding risks, label advice regarding dosing needs strict observation.