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. 2013;5(1):40-54.

Comparative effectiveness of novel oral anticoagulants for atrial fibrillation: evidence from pair-wise and warfarin-controlled network meta-analyses

G Biondi-Zoccai  1 , V Malavasi, F D'Ascenzo, A Abbate, P Agostoni, M Lotrionte, D Castagno, B Van Tassell, E Casali, M Marietta, M G Modena, K A Ellenbogen, G Frati
Affiliations

Comparative effectiveness of novel oral anticoagulants for atrial fibrillation: evidence from pair-wise and warfarin-controlled network meta-analyses

G Biondi-Zoccai et al. HSR Proc Intensive Care Cardiovasc Anesth. 2013.

Abstract

Introduction: Novel oral anticoagulants have been tested against warfarin for atrial fibrillation, yet no direct comparison is available. We thus aimed to perform pair-wise (direct) and warfarin-adjusted network (i.e. indirect) meta-analyses of novel oral anticoagulants for atrial fibrillation.

Methods: Databases were searched for randomized warfarin-controlled trials of novel anticoagulants for non-valvular atrial fibrillation. The primary end-point was long-term stroke/systemic embolism. Odds ratios (95% intervals) were computed with RevMan and WinBUGS.

Results: Seven trials (52701 patients) were included, focusing on apixaban, dabigatran, edoxaban and rivaroxaban. Pair-wise meta-analysis showed that after a weighted average of 23 months these novel anticoagulants lead to significant reductions in the risk of stroke/systemic embolism (odds ratio=0.81 [0.71-0.92], I2=23%) and all cause death (odds ratio=0.88 [0.82-0.95], I2=0%) in comparison to warfarin. Network meta-analysis showed that apixaban and dabigatran proved similarly superior to warfarin in preventing stroke/systemic embolism (odds ratio=0.78 [0.62-0.96] for apixaban vs warfarin; odds ratio=0.66 [0.52-0.84] for high-dose dabigatran vs warfarin; odds ratio for apixaban vs high-dose dabigatran=1.17 [0.85-1.63]), but apixaban was associated with fewer major bleedings (odds ratio=0.73 [0.57-0.93]) and drug discontinuations (odds ratio=0.64 [0.52-0.78]) than dabigatran. Rivaroxaban did not reduce stroke/systemic embolism (odds ratio=0.87 [0.71-1.07]) or major bleedings in comparison to warfarin (odds ratio=0.87 [0.71-1.07]) and was associated with more major bleedings in comparison to apixaban (odds ratio=1.52 [1.19-1.92]). Data for edoxaban were inconclusive.

Conclusions: Novel oral anticoagulants appear as a very promising treatment option for atrial fibrillation.

Keywords: apixaban; atrial fibrillation; dabigatran; meta-analysis; rivaroxaban; systematic review; warfarin.

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Conflict of interest statement

Disclosures Dr. Biondi-Zoccai has consulted/lectured for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly/Daiichi Sankyo, and Johnson & Johnson.

Figures

Table 1
Table 1
Pharmacokinetics of the novel oral anticoagulants.
Table 2
Table 2
Main features of included studies.
Table 3
Table 3
Key selection criteria of included studies.
Table 4
Table 4
Key patient characteristics of included studies.
Table 5
Table 5
Risk of bias assessment of included studies.
Table 6
Table 6
Key excluded studies.
Table 7
Table 7
Clinical outcomes in included studies*.
See this image and copyright information in PMC

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