{"title":"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》。","authors":"Pajaree Mongkhon, Noppaket Singkham, Kunyarat Ponok, Natpatsorn Liamsrijan, Wipada Phoosa, Sirayut Phattanasobhon, Laura Fanning, Vichai Senthong, Surasak Saokaew","doi":"10.1007/s40264-024-01476-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comparative Effectiveness and Safety of Off-Label Underdosed Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.\",\"authors\":\"Pajaree Mongkhon, Noppaket Singkham, Kunyarat Ponok, Natpatsorn Liamsrijan, Wipada Phoosa, Sirayut Phattanasobhon, Laura Fanning, Vichai Senthong, Surasak Saokaew\",\"doi\":\"10.1007/s40264-024-01476-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":11382,\"journal\":{\"name\":\"Drug Safety\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Safety\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40264-024-01476-8\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Safety","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40264-024-01476-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Comparative Effectiveness and Safety of Off-Label Underdosed Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.
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.
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.
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