Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
Sleep Med Rev. 2019 Aug;46:74-86. doi: 10.1016/j.smrv.2019.04.009. Epub 2019 Apr 19.
Pharmacotherapy represents a desirable potential therapeutic alternative for patients with obstructive sleep apnoea (OSA). We aimed to summarize evidence on the efficacy of pharmacotherapy in adults with OSA and delineate the underlying mechanisms. Seven databases were systematically screened for randomised controlled trials (RCTs) from their inception to September 2018. According to a pre-registered study protocol (PROSPERO-ID-CRD42018086446) network meta-analysis was performed to obtain intervention effects on the apnoea-hypopnoea-index (AHI) based on data extracted from published reports. We identified 58 RCTs (n = 1710 patients) investigating 44 different drugs or drug-combinations. Interventions were classified into seven pathomechanism-groups and summarized narratively. A meta-analysis of 17 trials for seven drugs (acetazolamide, donepezil, mirtazapine, ondansetron, paroxetine, protriptyline, theophylline) indicated a small effect for acetazolamide (mean difference in AHI -9.6/h [-17.7; -1.4]; p = 0.02). In the network meta-analysis (I = 50%) nine drugs (tramazoline, liraglutide, spironolactone/furosemide, acetazolamide, dronabinol, zonisamide, phentermine, spironolactone, and ondansetron/fluoxetine) significantly lowered the AHI compared to placebo. Although some trials indicate favorable outcomes, these results are only valid for distinctive OSA-phenotypes or were not clinically significant. The effect sizes were small, the majority of trials were not adequately powered. There is currently insufficient evidence to recommend any pharmacotherapy for OSA and no phase-III trials are available.
药物治疗代表了阻塞性睡眠呼吸暂停（OSA）患者一种理想的潜在治疗选择。我们旨在总结药物治疗成人 OSA 的疗效证据，并阐明潜在机制。从成立到 2018 年 9 月，我们系统地对七个数据库进行了随机对照试验（RCT）的筛选。根据预先注册的研究方案（PROSPERO-ID-CRD42018086446），对来自已发表报告的数据进行网络荟萃分析，以获得对呼吸暂停低通气指数（AHI）的干预效果。我们确定了 58 项 RCT（n=1710 名患者），研究了 44 种不同的药物或药物组合。干预措施分为七个发病机制组，并进行了叙述性总结。对七种药物（乙酰唑胺、多奈哌齐、米氮平、昂丹司琼、帕罗西汀、普罗替林、茶碱）的 17 项试验进行的荟萃分析表明，乙酰唑胺的效果较小（AHI 平均差异-9.6/h[-17.7; -1.4]; p=0.02）。在网络荟萃分析（I=50%）中，与安慰剂相比，有九种药物（曲马唑啉、利拉鲁肽、螺内酯/呋塞米、乙酰唑胺、大麻隆、唑尼沙胺、苯丙醇胺、螺内酯和昂丹司琼/氟西汀）显著降低了 AHI。尽管一些试验表明结果有利，但这些结果仅适用于特定的 OSA 表型，或者没有临床意义。效应大小较小，大多数试验的效力不足。目前没有足够的证据推荐任何药物治疗 OSA，也没有 III 期试验可用。
