Warfarin has been used as the only oral anticoagulant for over 50 years in patients with atrial fibrillation. Recently new oral anticoagulants like dabigatran, rivaroxaban and apixaban have been developed for this indication. We compared these new oral anticoagulants with each other and with warfarin with respect to efficacy and cost-effectiveness for patients with atrial fibrillation and moderate or high risk of stroke.

• The new oral anticoagulants reported statistically significant reductions of intracranial bleeding compared to warfarin. For the outcomes all-cause mortality, ischemic stroke, gastrointestinal bleeding and myocardial infarction, results were inconclusive. The quality of evidence for the outcomes was generally regarded as low or very low.
• Only one large randomised controlled trial presently exists for each of these three new oral anticoagulants, all compared to warfarin. This necessitated modelling through indirect comparisons.
• Apixaban 5 mg x 2, dabigatran 150 mg x 2 and rivaroxaban 20 mg x 1 all seems to be cost-effective when each are compared to warfarin for patients with atrial fibrillation at medium and high risk of stroke.
• When all drugs are compared to each other, dabigatran 150 mg x 2 seems to be the most cost-effective in 28 of 30 individual risk groups and apixaban in the remaining three risk groups based on an assumed threshold cost-effectivness of NOK 588 000 per QALY.
• The conclusions regarding efficacy and cost-effectiveness are highly uncertain. The conclusions may change if the assumptions in the model change. New research directly comparing the new oral anticoagulants with each other and with warfarin is likely to be useful and would reduce decision uncertainty.