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

Abstract

Background Apixaban, a non‐vitamin K oral anticoagulant ( NOAC ), was approved in Japan in 2012 for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation ( NVAF ). However, the safety and effectiveness of apixaban in clinical practice have not yet been elucidated thoroughly among Japanese NVAF patients. Methods 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 ( ADR s), hemorrhages, and thromboembolic events (ischemic stroke, systemic embolism [ SE ], and transient ischemic attack [ TIA ]). Results Among 6306 NVAF patients in the safety analysis set (age, 74.5 ± 10.1 years; women, 41.1%; and CHADS 2 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. ADR 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/ SE / TIA 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 NOAC s), incidence rates of major hemorrhage ( P = 0.221 for trend) and ischemic stroke/ SE / TIA ( P = 0.686 for trend) were comparable. Conclusions No new safety signals of apixaban were identified in Japanese NVAF patients. Safety and effectiveness of apixaban were consistent with those in the ARISTOTLE study.

One‐year clinical outcomes of anticoagulation therapy among Japanese patients with atrial fibrillation: The Hyogo AF Network (HAF‐NET) Registry

“…Furthermore, postmarketing studies for each DOAC also estimated that the proportion of an adjusted low dosing was almost 30% in the rivaroxaban or apixaban users and almost 60% in the dabigatran or edoxaban users. [19][20][21][22] The proportion of this estimated adequately low-dosing usage in the SAKURA registry was similar to our results. This indicated that the inadequate low dosing in the HAF-NET registry was extremely less than that in the previous AF registries.…”

“…The proportion of an adjusted low dosing was estimated to be almost 20% in the rivaroxaban or apixaban users and almost 50% in the dabigatran or edoxaban users. Furthermore, postmarketing studies for each DOAC also estimated that the proportion of an adjusted low dosing was almost 30% in the rivaroxaban or apixaban users and almost 60% in the dabigatran or edoxaban users . The proportion of this estimated adequately low‐dosing usage in the SAKURA registry was similar to our results.…”

Postmarketing surveillance on the clinical use of edoxaban in patients with nonvalvular atrial fibrillation (ETNA‐AF‐Japan): One‐year safety and effectiveness analyses

“…ETNA‐AF‐Japan included patients with CHADS 2 score ≤1, severe renal dysfunction (CLcr <30 mL/min) and DAPT use, which were excluded from ENGAGE AF‐TIMI 48 1 . Patient backgrounds such as age, body weight, and risk scores in terms of ETNA‐AF‐Japan were similar to those in the real‐world SAKURA AF Registry, 20,21 Fushimi AF Registry, 22 and other DOAC observational studies, 23‐27 suggesting that ETNA‐AF‐Japan reflected a real‐world population of Japanese patients with NVAF.…”

Safety and effectiveness of non-vitamin K oral anticoagulants versus warfarin in real-world patients with non-valvular atrial fibrillation: a retrospective analysis of contemporary Japanese administrative claims data

“…While RCTs are the gold standard for demonstrating the effectiveness of interventions, they are not fully representative of an unselected real-world population, thereby limiting the relevance of their findings to clinical practice. Consequently, a number of observational, real-world evidence studies have emerged to provide supportive evidence of the safety and/or effectiveness of NOACs in clinical practice 11–18. However, there remain several unmet knowledge gaps in the literature regarding the clinical outcomes of NOAC treatment in patients with NVAF, particularly in patient subgroups at high risk of adverse outcomes 19 20…”