Safety and effectiveness of apixaban in Japanese patients with nonvalvular atrial fibrillation in clinical practice: A regulatory postmarketing surveillance, the <scp>STANDARD</scp> study

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Apixaban, a non‐vitamin K oral anticoagulant (<jats:styled-content style="fixed-case">NOAC</jats:styled-content>), was approved in Japan in 2012 for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation (<jats:styled-content style="fixed-case">NVAF</jats:styled-content>). However, the safety and effectiveness of apixaban in clinical practice have not yet been elucidated thoroughly among Japanese <jats:styled-content style="fixed-case">NVAF</jats:styled-content> patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A postmarketing surveillance study was conducted to determine the safety and effectiveness of apixaban. Patients were followed‐up for 104 weeks. Outcome events included adverse drug reactions (<jats:styled-content style="fixed-case">ADR</jats:styled-content>s), hemorrhages, and thromboembolic events (ischemic stroke, systemic embolism [<jats:styled-content style="fixed-case">SE</jats:styled-content>], and transient ischemic attack [<jats:styled-content style="fixed-case">TIA</jats:styled-content>]).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among 6306 <jats:styled-content style="fixed-case">NVAF</jats:styled-content> patients in the safety analysis set (age, 74.5 ± 10.1 years; women, 41.1%; and <jats:styled-content style="fixed-case">CHADS</jats:styled-content><jats:sub>2</jats:sub> score, 2.0 ± 1.4), 3600 patients (57.1%) received the standard dose (5 mg twice daily) and 2694 (42.7%) received a reduced dose (2.5 mg twice daily) of apixaban. <jats:styled-content style="fixed-case">ADR</jats:styled-content>s occurred in 604 patients (9.58%), with the most common being epistaxis (0.86%), subcutaneous hemorrhage (0.67%), and hematuria (0.57%). Incidence rate of any hemorrhages and major hemorrhage was 5.52% per year and 2.36% per year, respectively. Incidence rate of ischemic stroke/<jats:styled-content style="fixed-case">SE</jats:styled-content>/<jats:styled-content style="fixed-case">TIA</jats:styled-content> was 1.00% per year among 6286 patients in the effectiveness analysis set. Among three subgroups (3106 apixaban initiators, 2038 patients switched from warfarin, and 1118 patients switched from other <jats:styled-content style="fixed-case">NOAC</jats:styled-content>s), incidence rates of major hemorrhage (<jats:italic>P</jats:italic> = 0.221 for trend) and ischemic stroke/<jats:styled-content style="fixed-case">SE</jats:styled-content>/<jats:styled-content style="fixed-case">TIA</jats:styled-content> (<jats:italic>P</jats:italic> = 0.686 for trend) were comparable.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>No new safety signals of apixaban were identified in Japanese <jats:styled-content style="fixed-case">NVAF</jats:styled-content> patients. Safety and effectiveness of apixaban were consistent with those in the <jats:styled-content style="fixed-case">ARISTOTLE</jats:styled-content> study.</jats:p></jats:sec>