Comparative Effectiveness and Safety of Off-Label Underdosed Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

IF 4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Safety Pub Date : 2024-08-30 DOI:10.1007/s40264-024-01476-8

Pajaree Mongkhon, Noppaket Singkham, Kunyarat Ponok, Natpatsorn Liamsrijan, Wipada Phoosa, Sirayut Phattanasobhon, Laura Fanning, Vichai Senthong, Surasak Saokaew

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Abstract

Introduction: Off-label underdosed direct oral anticoagulants (DOACs) are commonly utilised in Asian patients with atrial fibrillation (AF) since they are prone to bleeding with OACs. However, the efficacy and safety of off-label underdosing DOACs are controversial. This study aimed to compare the effectiveness and safety of off-label underdosed DOACs in Asian patients with AF.

Methods: PubMed, Embase, Cochrane library, and ClinicalTrials.gov were searched from 2010 to July 5, 2024, for randomised controlled trials or observational studies that compared off-label DOACs and on-label/warfarin in Asian patients with AF. The primary outcomes included ischaemic stroke or systemic embolism (ISSE) and major bleeding (MB), while secondary outcomes included all-cause death, gastrointestinal bleeding (GIB), intracranial haemorrhage (ICH), and myocardial infarction (MI). Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models.

Results: Twenty observational studies were included. Seventeen studies compared off-label underdosed DOACs versus on-label DOACs, whereas five studies compared off-label underdosed DOACs versus warfarin. Off-label underdosed DOACs were associated with higher risk of ISSE (pooled HR [pHR] = 1.17; 95% CI: 1.00-1.38, p = 0.048) and ICH (pHR = 1.27; 95% CI: 1.06-1.52, p = 0.010) versus on-label. Subgroup analysis demonstrated increased ISSE risk with off-label underdosed rivaroxaban compared to on-label (pHR = 1.49; 95% CI: 1.07-2.08). Compared to warfarin, off-label underdosed DOACs were associated with decreased risk of MB (pHR = 0.46; 95% CI: 0.32-0.65, p < 0.001), GIB (pHR = 0.52; 95% CI: 0.29-0.93, p = 0.028), ICH (pHR = 0.60; 95% CI: 0.42-0.86, p = 0.005), and all-cause death (pHR = 0.70; 95% CI: 0.56-0.87, p = 0.001), while illustrating similar ISSE risk.

Conclusions: Off-label underdosed DOACs, particularly rivaroxaban, was associated with increased ISSE risk but did not decrease bleeding compared to on-label. Adherence to appropriate DOAC doses should be emphasised to achieve the best clinical outcomes for Asian patients with AF.

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标签外剂量不足的直接口服抗凝药在亚洲心房颤动患者中的疗效和安全性比较：系统回顾与元分析》。

简介：标签外剂量不足的直接口服抗凝药（DOACs）通常用于亚洲心房颤动（AF）患者，因为他们服用 OACs 后容易出血。然而，标签外剂量不足的 DOACs 的有效性和安全性尚存争议。本研究旨在比较标签外剂量不足的 DOACs 在亚洲房颤患者中的有效性和安全性：方法：检索了 PubMed、Embase、Cochrane 图书馆和 ClinicalTrials.gov（2010 年至 2024 年 7 月 5 日）中对标签外 DOAC 与标签内/华法林在亚洲房颤患者中的应用进行比较的随机对照试验或观察性研究。主要结果包括缺血性卒中或全身性栓塞（ISSE）和大出血（MB），次要结果包括全因死亡、消化道出血（GIB）、颅内出血（ICH）和心肌梗死（MI）。采用随机效应模型对危险比（HRs）及95%置信区间（CIs）进行了汇总：共纳入 20 项观察性研究。17项研究比较了标签外剂量不足的DOAC与标签内剂量不足的DOAC，5项研究比较了标签外剂量不足的DOAC与华法林。标签外剂量不足的 DOAC 与标签内剂量不足的 DOAC 相比，发生 ISSE（集合 HR [pHR] = 1.17；95% CI：1.00-1.38，p = 0.048）和 ICH（pHR = 1.27；95% CI：1.06-1.52，p = 0.010）的风险更高。亚组分析表明，标签外剂量不足的利伐沙班与标签内相比，ISSE 风险增加（pHR = 1.49；95% CI：1.07-2.08）。与华法林相比，标签外剂量不足的 DOACs 与 MB（pHR = 0.46；95% CI：0.32-0.65，p < 0.001）、GIB（pHR = 0.52；95% CI：0.29-0.93，p = 0.028）、ICH（pHR = 0.60；95% CI：0.42-0.86，p = 0.005）和全因死亡（pHR = 0.70；95% CI：0.56-0.87，p = 0.001），同时说明ISSE风险相似：标示外剂量不足的DOACs，尤其是利伐沙班，与标示内相比，与ISSE风险增加相关，但出血量并未减少。为使亚洲房颤患者获得最佳临床疗效，应强调坚持使用适当剂量的 DOAC。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Safety 医学-毒理学

CiteScore

7.60

自引率

7.10%

发文量

112

审稿时长

6-12 weeks

期刊介绍： Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes: Overviews of contentious or emerging issues. Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes. In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area. Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics. Editorials and commentaries on topical issues. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.