Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a 'real world' atrial fibrillation population: A modelling analysis based on a nationwide cohort study.

Banerjee A, Lane DA, Torp-Pedersen C, Lip GY.
Thromb Haemost. 2012 Mar 1;107(3):584-9.

Background

The concept of net clinical benefit is used to quantify the balance between the risk of ischemic stroke and the risk of intracranial hemorrhage during the use of oral anticoagulants in nonvalvular atrial fibrillation. It has been shown that patients with the highest risk of stroke and thromboembolism have the greatest benefit of oral anticoagulation with warfarin [1]. For the new oral anticoagulants, the net clinical benefit in a normal population is not yet known. In this study, with data from the Danish National Patient Registry [2] by using a model the expected net clinical benefit of dabigatran, rivaroxaban and apixaban was calculated based on recent clinical trial results.

Main results

The new oral anticoagulants apixaban, dabigatran and rivaroxaban have a greater net clinical benefit than warfarin in patients with atrial fibrillation who are at high risk of stroke (CHA2DS2 Vasc-score of 2 or more). In patients with a lower risk of stroke but with a high risk of bleeding apixaban and dabigatran 110 mg bid had a positive net clinical benefit. In patients at average risk (CHA2DS2-Vasc = 1), the net clinical benefit is especially beneficial with apixaban and both doses of dabigatran (110 mg and 150 mg bid). When both the risk of stroke and risk of bleeding are high, all three drugs have a greater net clinical benefit than warfarin.

Conclusion

In the absence of head-to-head studies, this analysis can help in selecting an oral anticoagulant for the prevention of stroke in atrial fibrillation.

Editorial comment [3]

This analysis is a unique approach to compare warfarin with new oral anticoagulants. The study does not indicate which specific drug should be used in an individual patient. Therefore long-term results are needed of each drug.

References

1. Singer DE, Chang Y, Fang MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009; 151: 297–305.
2. Olesen JB, Lip GY, Lindhardsen J, et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a 'real world' nationwide cohort study. Thromb Haemost 2011; 106:739–749.
3. Goldhaber SZ. What's the "go to" anticoagulant for stroke prevention in atrial fibrillation? Thromb Haemost 2012; 107:397-398.

Abstract

The concept of net clinical benefit has been used to quantify the balance between risk of ischaemic stroke (IS) and risk of intracranial haemorrhage (ICH) with the use oral anticoagulant therapy (OAC) in the setting of non-valvular atrial fibrillation (AF), and has shown that patients at highest risk of stroke and thromboembolism gain the greatest benefit from OAC with warfarin. There are no data for the new OACs, that is, dabigatran, rivaroxaban and apixaban, as yet. We calculated the net clinical benefit balancing IS against ICH using data from the Danish National Patient Registry on patients with non-valvular AF between 1997-2008, for dabigatran, rivaroxaban and apixaban on the basis of recent clinical trial outcome data for these new OACs. In patients with CHADS2=0 but at high bleeding risk, apixaban and dabigatran 110 mg bid had a positive net clinical benefit. At CHA2DS2-VASc=1, apixaban and both doses of dabigatran (110 mg and 150 mg bid) had a positive net clinical benefit. In patients with CHADS2 score≥1 or CHA2DS2-VASc≥2, the three new OACs (dabigatran, rivaroxaban and apixaban) appear superior to warfarin for net clinical benefit, regardless of risk of bleeding. When risk of bleeding and stroke are both high, all three new drugs appear to have a greater net clinical benefit than warfarin. In the absence of head-to-head trials for these new OACs, our analysis may help inform decision making processes when all these new OACs become available to clinicians for stroke prevention in AF. Using 'real world' data, our modelling analysis has shown that when the risk of bleeding and stroke are both high, all three new drugs appear to have a greater net clinical benefit compared to warfarin.