Meta-Analysis of Effectiveness and Safety of Oral Anticoagulants in Atrial Fibrillation With Focus on Apixaban

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We performed a meta-analysis of data on the effectiveness and safety of apixaban compared with other oral anticoagulants (warfarin or rivaroxaban or dabigatran or edoxaban) for stroke prevention in atrial fibrillation (AF) in different settings of randomized controlled trials, real-world studies, and radiofrequency ablation (RFA). Thirty studies were searched in PubMed, the Cochrane Library, and Clinicaltrials.gov databases reporting comparative effectiveness and safety of apixaban with warfarin (n = 23), rivaroxaban (n = 12), dabigatran (n = 13), or edoxaban (n = 2) for stroke prevention in AF. In real-world estimates, apixaban was similar to warfarin for the prevention of stroke or systematic thromboembolism (hazard ratio 0.93, 95% CI 0.71 to 1.14, I2 = 82.9%, N = 7), and safer than warfarin in the risks of major bleeding (hazard ratio 0.62, 95% CI 0.54 to 0.70, I2 = 18.7%, N = 9) in patients with AF. The risk of stroke or thromboembolism with apixaban was similar to rivaroxaban, dabigatran, and edoxaban in the settings of real-world studies and RFA. Major bleeding with apixaban was generally lower than rivaroxaban (relative risks 0.45, 95% CI 0.38 to 0.53, I2 = 0%, N = 5) and similar to dabigatran in real-world studies (relative risks 1.44, 95% CI 0.33 to 6.30, I2 = 97.7%, N = 5), but similar to rivaroxaban, dabigatran, and edoxaban in RFA. In conclusion, our meta-analysis provides a comprehensive estimate of the effectiveness and safety of apixaban compared with other oral anticoagulants (warfarin, rivaroxaban, dabigatran, and edoxaban) in patients with AF in different settings of randomized controlled trial, real-world studies, and RFA.

Section snippets

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the reporting Meta-analyses of Observational Studies in Epidemiology when performing this meta-analysis.4, 5

A comprehensive search of PubMed, the Cochrane Library, and Clinicaltrials.gov databases was performed by 2 independent reviewers (YB and X-BS) using the following items: “atrial fibrillation” OR “AF” AND “apixaban” OR “rivaroxaban” OR “dabigatran” OR “edoxaban” OR “warfarin” OR “NOAC” OR “DOAC” AND

Results

A total of 1,936 studies were initially identified. After screening titles and abstracts, we excluded 1,863 papers, and 73 remained for detailed evaluation. Of these, 42 were excluded as they did not meet the inclusion criteria (7 reviews and meta-analysis; 7 papers without outcomes of OACs; 9 papers without separate information on apixaban, rivaroxaban, dabigatran, or edoxaban; 12 studies with duplicate data, 1 on the setting of direct current cardioversion; and 7 with mixed diseases except

Discussion

In this meta-analysis, our principal findings are as follows: (1) apixaban was associated with similar effectiveness of stroke or TE prevention compared with warfarin, dabigatran, rivaroxaban, and edoxaban in real-world studies, and RFA; (2) apixaban had similar safety to warfarin, rivaroxaban, dabigatran, and edoxaban for major bleeding in the setting of RFA, but was safer than warfarin in RCTs and real-world studies; (3) apixaban was safer than rivaroxaban in real-world studies, and had

Disclosures

C-SM has received honoraria from Bristol-Myers Squibb (BMS), Pfizer, Johnson & Johnson, Boehringer Ingelheim (BI), and Bayer for giving lectures.

GYHL has served as a consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife, and Daiichi-Sankyo, and as a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche, and Daiichi-Sankyo.

Other authors declare no conflict of interest.

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    Funding: This work was supported by grants from Beijing Tongren Hospital, Capital Medical University (2016-YJJ-BJRC-010), the National Natural Science Fund (81470464 and 81530016), and the Ministry of Science and Technology (2016YFC0900901).

    See page 1694 for disclosure information.

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