DAHOS Study: Efficacy of dapagliflozin in treating heart failure with reduced ejection fraction and obstructive sleep apnea syndrome - A 3-month, multicenter, randomized controlled clinical trial.

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2024-05-01 Epub Date: 2024-02-22 DOI:10.1007/s00228-024-03643-3

Liang Xie, Shengnan Li, Xiaojin Yu, Qin Wei, Fuchao Yu, Jiayi Tong

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引用次数: 0

Abstract

Background: The recent discovery of new therapeutic approaches to heart failure with reduced ejection fraction (HFrEF), including sodium-glucose cotransporter-2 (SGLT-2) inhibitors, as well as improved treatment of co-morbidities has provided much needed help to HFrEF. In addition, dapagliflozin, one of the SGLT-2 inhibitors, serves as a promising candidate in treating obstructive sleep apnea (OSA) of HFrEF patients due to its likely mechanism of countering the pathophysiology of OSA of HFrEF.

Methods: This 3-month multicenter, prospective, randomized controlled trial enrolled participants with left ventricular ejection fraction (LVEF) less than 40% and apnea-hypopnea index (AHI) greater than 15. Participants were randomized into two groups: the treatment group received optimized heart failure treatment and standard-dose dapagliflozin, while the control group only received optimized heart failure treatment. The primary endpoint was the difference in AHI before and after treatment between the two groups. Secondary endpoints included oxygen desaturation index (ODI), minimum oxygen saturation, longest apnea duration, inflammatory factors (CRP, IL-6), quality of life score, and LVEF.

Results: A total of 107 patients were included in the final analysis. AHI, LVEF and other baseline data were similar for the dapagliflozin and control groups. After 12 weeks of dapagliflozin treatment, the dapagliflozin group showed significant improvements in sleep parameters including AHI, HI, longest pause time, ODI, time spent with SpO₂ < 90%, and average SpO₂. Meanwhile, the control group showed no significant changes in sleep parameters, but did demonstrate significant improvements in left ventricular end-diastolic diameter, LVEF, and NT-proBNP levels at 12 weeks. In the experimental group, BMI was significantly reduced, and there were improvements in ESS score, MLHFQ score, and EQ-5D-3L score, as well as significant reductions in CRP and IL-6 levels, while the CRP and IL-6 levels were not improved in the control group. The decrease in LVEF was more significant in the experimental group compared to the control group. There were no significant differences in the magnitude of the decreases between the two groups.

Conclusions: Dapagliflozin may be an effective treatment for heart failure complicated with OSA, and could be considered as a potential new treatment for OSA. (Trial registration www.chictr.org.cn , ChiCTR2100049834. Registered 10 August 2021).

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DAHOS 研究：达帕格列净治疗射血分数降低型心力衰竭合并阻塞性睡眠呼吸暂停综合征的疗效--一项为期 3 个月的多中心随机对照临床试验。

背景：最近发现了射血分数降低型心力衰竭（HFrEF）的新治疗方法，包括钠-葡萄糖共转运体-2（SGLT-2）抑制剂，并改善了合并疾病的治疗，这为 HFrEF 提供了急需的帮助。此外，SGLT-2 抑制剂之一的达帕格列净（dapagliflozin）是治疗 HFrEF 患者阻塞性睡眠呼吸暂停（OSA）的有望候选药物，因为它可能具有对抗 HFrEF OSA 病理生理学的机制：这项为期 3 个月的多中心、前瞻性随机对照试验招募了左心室射血分数（LVEF）小于 40%、呼吸暂停-低通气指数（AHI）大于 15 的参与者。参与者被随机分为两组：治疗组接受优化的心衰治疗和标准剂量达帕格列净，而对照组只接受优化的心衰治疗。主要终点是两组治疗前后 AHI 的差异。次要终点包括氧饱和度指数（ODI）、最低氧饱和度、最长呼吸暂停持续时间、炎症因子（CRP、IL-6）、生活质量评分和 LVEF：共有 107 名患者被纳入最终分析。达帕格列净组和对照组的AHI、LVEF和其他基线数据相似。达帕格列净治疗12周后，达帕格列净组的AHI、HI、最长暂停时间、ODI、SpO2 2耗时等睡眠参数均有显著改善。与此同时，对照组的睡眠参数没有明显变化，但在 12 周时左心室舒张末期直径、LVEF 和 NT-proBNP 水平有明显改善。实验组的 BMI 显著降低，ESS 评分、MLHFQ 评分和 EQ-5D-3L 评分均有改善，CRP 和 IL-6 水平显著降低，而对照组的 CRP 和 IL-6 水平没有改善。与对照组相比，实验组 LVEF 的下降更为显著。两组的下降幅度无明显差异：达帕格列净可有效治疗合并OSA的心力衰竭，可作为OSA的一种潜在新疗法。(试验注册 www.chictr.org.cn , ChiCTR2100049834。注册日期：2021 年 8 月 10 日）。

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

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.