Abstract
Safe and effective stroke prevention in atrial fibrillation (AF) is crucial as the number of patients with this condition continues to increase. Several novel oral anticoagulants are being developed as replacements for warfarin for this indication. Direct factor Xa inhibitors comprise the largest class of oral anticoagulants in development; the inhibition of factor Xa is recognized to be a promising target for therapeutic anticoagulation, partly because of its location in the coagulation cascade. Apixaban, betrixaban, edoxaban, and rivaroxaban are small-molecule, selective inhibitors that directly and reversibly bind to the active site of factor Xa. Their pharmacokinetic and pharmacodynamic profiles vary, which might allow patient-specific therapy. Several of these agents have been tested in clinical trials for various indications, including AF, with favorable results. In particular, apixaban and rivaroxaban have shown superiority and noninferiority, respectively, to warfarin in phase III clinical trials for stroke prevention in AF. These agents have also been shown to be safe in terms of bleeding risk. Despite these advantages, factor Xa inhibitors have several characteristics, such as potential interactions with other drugs (inhibitors of cytochrome P450 and P-glycoprotein) and the inability to reverse their anticoagulant effects, as well as concerns about poor patient compliance, which must be considered when initiating patients on a novel factor Xa inhibitor.
Key Points
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Vitamin K antagonists, such as warfarin, are difficult to manage and, therefore, often underused for stroke prevention in patients with atrial fibrillation (AF)
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Direct factor Xa inhibitors are the largest class of novel oral anticoagulants in development; several phase III clinical trials have been completed with these agents for stroke prevention in AF
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In a phase III trial, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism, without a significant difference in major bleeding
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In a phase III trial, apixaban was superior to warfarin for the prevention of stroke or systemic embolism, with a significant decrease in major bleeding and all-cause mortality
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Oral factor Xa inhibitors present several clinical challenges (inability to reverse their anticoagulant effects, poor patient compliance, and the need for monitoring), which must be considered when selecting therapy
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J. Ansell is, or has been, a consultant for Boehringer Ingelheim, Bristol–Myers Squibb, Daiichi Sankyo, and Janssen. K. P. Cabral declares no competing interests.
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Cabral, K., Ansell, J. Oral direct factor Xa inhibitors for stroke prevention in atrial fibrillation. Nat Rev Cardiol 9, 385–391 (2012). https://doi.org/10.1038/nrcardio.2012.19
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DOI: https://doi.org/10.1038/nrcardio.2012.19
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