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Comparative Effectiveness and Safety of Direct Oral Anticoagulants: Overview of Systematic Reviews

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Abstract

Direct oral anticoagulants are now recommended by major guidelines as first-choice agents for both stroke prevention in non-valvular atrial fibrillation and treatment/prevention of venous thromboembolism in non-cancer patients. Although there are no published head-to-head trials comparing different direct oral anticoagulants, a growing body of evidence from indirect comparisons and observational studies is suggesting that each direct oral anticoagulant may have a specific risk profile. This review aims to (1) synthesize and critically assess the latest evidence in comparative effectiveness and safety research in the aforementioned consolidated therapeutic uses, by performing an overview of systematic reviews and (2) highlight current challenges, namely underexplored areas, where research should be directed, also considering ongoing unpublished studies. The evidence gathered so far on the risk–benefit profile of direct oral anticoagulants is appraised in the light of existing guidelines to discuss whether further implementation should be proposed.

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Authors and Affiliations

  1. Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy

    Emanuel Raschi, Matteo Bianchin, Milo Gatti & Fabrizio De Ponti

  2. Research Center on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Varese, Italy

    Alessandro Squizzato

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  1. Emanuel Raschi
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  2. Matteo Bianchin
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  3. Milo Gatti
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Contributions

ER conceived the idea and the overall content of this review, performed the literature search and data analysis, and drafted and critically revised the work. MB provided a substantial contribution to data analysis. All authors critically revised the content and approved the final version of the manuscript.

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Correspondence to Emanuel Raschi.

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Funding

Emanuel Raschi, Matteo Bianchin, Milo Gatti, and Fabrizio De Ponti at the University of Bologna are supported by institutional research funds (Ricerca Fondamentale Orientata). No sources of funding were received for the preparation of this article.

Conflict of interest

Emanuel Raschi, Matteo Bianchin, Milo Gatti, and Fabrizio De Ponti have no conflicts of interest that are directly relevant to the content of this article. Alessandro Squizzato received fees for lectures and advisory board meetings from Daiichi Sankyo, Pfizer, Bristol Myers Squibb, Bayer, Boehringer Ingelheim, Sanofi, and Techdow.

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Raschi, E., Bianchin, M., Gatti, M. et al. Comparative Effectiveness and Safety of Direct Oral Anticoagulants: Overview of Systematic Reviews. Drug Saf 42, 1409–1422 (2019). https://doi.org/10.1007/s40264-019-00866-7

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