Summary
New oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention
of stroke in patients with non-valvular atrial fibrillation. Two agents are direct
factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin
inhibitor (dabigatran). They have been separately compared to warfarin in large randomised
trials. Our objective was to indirectly compare the three agents to each other for
major efficacy and safety outcomes. Studies were assessed for comparability and the
odds ratios of selected outcomes for each anticoagulant versus one another were estimated
indirectly. The three cohorts differed significantly in terms of CHADS2 score and the number of individuals with a past history of stroke, transient ischemic
attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism
was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus
dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88
for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban
(p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus
dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02),
0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran
110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion,
the available data indicate no significant difference in efficacy between dabigatran
150 mg and apixaban for the prevention of stroke or systemic embolism in patients
with non-valvular atrial fibrillation. It appears however that apixaban is associated
with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban
is less effective than dabigatran 150 mg in preventing stroke or systemic embolism.
Such an indirect comparison should be used only to generate hypotheses which need
to be tested in a dedicated randomised trial comparing the three drugs directly.
Keywords
Atrial fibrillation - anticoagulants - stroke