替尔泊肽治疗阻塞性睡眠呼吸暂停：试验证据、心脏代谢效应及对心血管实践的意义

文献信息

中文摘要

背景： 阻塞性睡眠呼吸暂停影响全球约十亿成年人，并与高血压、心房颤动、心力衰竭和卒中相关。肥胖是其主要的可逆病因，然而气道正压治疗只是支撑咽部气道，并未解决导致气道狭窄的脂肪堆积问题，随机试验也未显示其能减少心血管事件。2024年12月，美国食品药品监督管理局批准替尔泊肽——一种葡萄糖依赖性促胰岛素多肽和胰高血糖素样肽-1受体双重激动剂——作为首个用于肥胖成人中重度阻塞性睡眠呼吸暂停的药物。方法：我们总结了替尔泊肽的药理学以及体重减轻改善上气道通畅性的解剖学基础，尤其是舌和咽旁脂肪的减少。随后我们回顾了SURMOUNT-OSA项目：两项平行的52周、双盲、安慰剂对照3期试验，纳入469名肥胖且呼吸暂停低通气指数至少为每小时15次事件的成年人，一项未使用气道正压治疗，另一项在已建立气道正压治疗期间进行。结果：与安慰剂相比，替尔泊肽使呼吸暂停低通气指数估计分别减少每小时20.0和23.8次事件，同时睡眠呼吸暂停特异性缺氧负荷、体重、收缩压和高敏C反应蛋白也相应降低。结论：替尔泊肽可改善肥胖合并阻塞性睡眠呼吸暂停患者的呼吸暂停低通气指数及相关指标，但其对心血管结局的影响仍需进一步研究。

英文摘要

Obstructive sleep apnea affects approximately one billion adults worldwide and is associated with hypertension, atrial fibrillation, heart failure, and stroke. Obesity is its dominant reversible cause, yet positive airway pressure therapy splints the pharyngeal airway without addressing the adiposity that narrows it, and randomized trials have not shown that it reduces cardiovascular events. In December 2024, the United States Food and Drug Administration approved tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as the first drug for moderate-to-severe obstructive sleep apnea in adults with obesity. We summarize the pharmacology of tirzepatide and the anatomic basis by which weight reduction improves upper airway patency, notably reduction of tongue and parapharyngeal fat. We then review the SURMOUNT-OSA program: two parallel 52-week, double-blind, placebo-controlled phase 3 trials enrolling 469 adults with obesity and an apnea-hypopnea index of at least 15 events per hour, one conducted without positive airway pressure and one during established positive airway pressure use. Tirzepatide reduced the apnea-hypopnea index by an estimated 20.0 and 23.8 events per hour relative to placebo, with concurrent reductions in sleep apnea-specific hypoxic burden, body weight, systolic blood pressure, and high-sensitivity C-reactive protein.