Clinical outcomes of off-label DOAC underdosing in Japanese patients with atrial fibrillation: a systematic review and meta-analysis.

IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Akinori Sairaku, Yuka Kimura, Yukiko Nakano
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引用次数: 0

Abstract

Japanese patients with atrial fibrillation (AF) often receive underdosed direct oral anticoagulants (DOACs), deviating from standard guidelines. The impact of underdosing compared to standard dosing on thromboembolic and bleeding risks in this population remains unclear. This meta-analysis included 13 studies with 37,633 Japanese AF patients comparing underdose and standard dose groups. Efficacy outcomes included stroke or systemic embolism and ischemic stroke. Safety outcomes were major bleeding, intracranial hemorrhage, gastrointestinal bleeding, all bleeding, and all-cause mortality. Hazard ratios and 95% confidence intervals were pooled using a random-effects model. Sensitivity analyses evaluated robustness by including studies with confounder controls. Underdosing showed similar risks of stroke or systemic embolism (HR 1.03, 95% CI 0.87-1.22) and ischemic stroke (HR 1.05, 95% CI 0.85-1.31) compared to standard dosing. Major bleeding (HR 0.86; 95% CI 0.72-1.04) and all bleeding (HR 0.80; 95% CI 0.63-1.03) showed a non-significant reduction with underdosing. Sensitivity analyses confirmed a significant reduction in major bleeding risk with underdosing (HR 0.77, 95% CI 0.64-0.94). All-cause mortality was significantly higher in the underdose group throughout the primary (HR 1.47, 95% CI 1.13-1.90) and sensitivity analyses. In conclusion, Japanese patients receiving an underdose of DOACs had thromboembolic event rates comparable to those seen with standard dosing, with a reduction in bleeding events confirmed by sensitivity analyses and higher mortality. These findings indicate that ethnic-specific factors may influence DOAC effects, warranting further investigation to validate these observations and inform tailored dosing recommendations for Japanese AF patients.

日本房颤患者超说明书DOAC剂量不足的临床结果:系统回顾和荟萃分析
日本心房颤动(AF)患者经常接受剂量不足的直接口服抗凝剂(DOACs),偏离标准指南。与标准剂量相比,低剂量对该人群血栓栓塞和出血风险的影响尚不清楚。这项荟萃分析包括13项研究,涉及37,633名日本房颤患者,比较低剂量组和标准剂量组。疗效结果包括中风或全身性栓塞和缺血性中风。安全性结局为大出血、颅内出血、胃肠道出血、全出血和全因死亡率。使用随机效应模型合并风险比和95%置信区间。敏感性分析通过纳入混杂对照研究来评估稳健性。与标准剂量相比,剂量不足显示出相似的卒中或全身栓塞风险(HR 1.03, 95% CI 0.87-1.22)和缺血性卒中风险(HR 1.05, 95% CI 0.85-1.31)。大出血(HR 0.86;95% CI 0.72-1.04)和所有出血(HR 0.80;95% CI 0.63-1.03)显示剂量不足导致无显著降低。敏感性分析证实,剂量不足可显著降低大出血风险(HR 0.77, 95% CI 0.64-0.94)。在整个初始分析和敏感性分析中,剂量不足组的全因死亡率显著较高(HR 1.47, 95% CI 1.13-1.90)。总之,接受DOACs剂量不足的日本患者的血栓栓塞事件发生率与标准剂量的患者相当,敏感性分析证实出血事件减少,死亡率更高。这些发现表明,种族特异性因素可能影响DOAC的效果,需要进一步的研究来验证这些观察结果,并为日本房颤患者提供量身定制的剂量建议。
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来源期刊
CiteScore
9.20
自引率
0.00%
发文量
112
审稿时长
4-8 weeks
期刊介绍: The Journal of Thrombosis and Thrombolysis is a long-awaited resource for contemporary cardiologists, hematologists, vascular medicine specialists and clinician-scientists actively involved in treatment decisions and clinical investigation of thrombotic disorders involving the cardiovascular and cerebrovascular systems. The principal focus of the Journal centers on the pathobiology of thrombosis and vascular disorders and the use of anticoagulants, platelet antagonists, cell-based therapies and interventions in scientific investigation, clinical-translational research and patient care. The Journal will publish original work which emphasizes the interface between fundamental scientific principles and clinical investigation, stimulating an interdisciplinary and scholarly dialogue in thrombosis and vascular science. Published works will also define platforms for translational research, drug development, clinical trials and patient-directed applications. The Journal of Thrombosis and Thrombolysis'' integrated format will expand the reader''s knowledge base and provide important insights for both the investigation and direct clinical application of the most rapidly growing fields in medicine-thrombosis and vascular science.
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