Should it replace oral anticoagulant treatment in patients with atrial fibrillation?
Dabigatran is an oral thrombin inhibitor, which until now has been approved for the prevention of venous thrombosis in adults that have undergone hip or knee alloplastic surgery. It has recently been approved for the prevention of apoplexy and systemic embolism in adults with non-valvular atrial fibrillation, that in addition also carry one or more risk factors for apoplexy. Dabigatran is given as a standard dose of 150 mg twice daily in patients below 80 years, and 110 mg twice daily in patients above 80 years. Dabigatran is contraindicated in patients with severe renal impairment (GFR<30 ml/min). There is no need for biochemical monitoring of the anticoagulant effect.
The use of dabigatran has been examined in the RELY study, which has been reviewed by the IRF in 2009. In the study, dabigatran 110 mg twice daily and dabigatran 150 mg twice daily was compared to warfarin. In both dosages, dabigatran was found to have no less effect than warfarin. Dabigatran 150 mg twice daily showed less risk of apoplexy and systemic embolism, while 110 mg twice daily showed less risk of larger bleedings, including the severe intracranial types. An unexpected, slight numerical increase in the incident of myocardial infarctions was seen in dabigatran treated patients, which has prompted a sharpened surveillance of this adverse effect.
IRF finds, that dabigatran can be chosen as an anticoagulant in patients with non-valvular atrial fibrillation, including before and after DC-conversion. Dabigatran is preferred for patients with difficulties in following a classical anticoalulant treatment with warfarin, that are difficult to monitor, or where there are significant risks for interactions with warfarin.
Patients that are in well-controlled treatment with warfarin will only have a marginal benefit of a change to dabigatran.
NNT for clinical net effect (reduction of embolisms and a decrease in risk of bleeding) per year is calculated to be 125 compared to warfarin, and will, in medical expenses only, cost about 800.000 Dkr. per clinical event (apoplexy or embolism) postponed. Theoretically, a corresponding amount could be saved with reductions in clinical controls and INR measurements, assuming that the free capacity and available resources are not used for something else, and also assuming a reduction in public expenses of 180 million Dkr. for the GP’s (about 50.000 Dkr per GP), and a reduction of 120 million Dkr. for the hospitals.
Institute for Rational Pharmacotherapy, August 23rd, 2011.