Bady Zeyad, Mohammed Hazem E, Aboeldahab Heba, Samir Mahmoud, Aissani Mohamed Smail, Mohamed-Hussein Aliaë A R
Faculty of Medicine, Assiut University, Assiut, Egypt.
Medical Research Group of Egypt (MRGE), Negida Academy, Cairo, Egypt.
Sleep Breath. 2024 Dec 23;29(1):63. doi: 10.1007/s11325-024-03227-6.
Noradrenergics and antimuscarinics have been proposed as future pharmacotherapy for obstructive sleep apnea (OSA). However, the available randomized controlled trials (RCTs) showed heterogeneous results regarding the safety and efficacy of the combined regimen in OSA. Therefore, we performed this meta-analysis from the published RCTs to clarify this conflicting evidence.
A systematic search of four electronic databases was done till December 2023.
Thirteen RCTs (n = 345) were systematically reviewed and meta-analyzed. The combined regimen significantly reduced apnea-hypopnea index (AHI): AHI 3% [events/h; Mean difference (MD): - 6.30; 95% Confidence interval (CI) (- 9.74, - 2.87); P = 0.0003], AHI 4% [events/h; MD: - 6.50; 95% CI (- 8.74, - 4.26 events/h); P < 0.00001]. All gasometric measures significantly improved in the combined regimen group except mean SpO2. No difference was found in total sleep time between the treatment and placebo. However, compared to placebo, the combined regimen altered sleep architecture and decreased sleep efficiency. Regarding OSA endotypes, the combined regimen significantly improved loop gain, pharyngeal muscle compensation, pharyngeal muscle recruitment, and respiratory arousal threshold.
The combined regimen effectively reduces AHI and OSA severity with improvement in almost all OSA endotypes. However, this regimen decreased sleep efficiency and altered sleep architecture. Short-term side effects can be confined to increased heart rate, dry mouth and urinary hesitancy. Therefore, noradrenergics and anti-muscarinics is a promising regimen for treating OSA, yet this optimism must be titrated by the lack of long-term effects of the regimen. Future RCTs with focus on the long-term efficacy of the regimen and cardiovascular outcomes is recommended.
去甲肾上腺素能药物和抗毒蕈碱药物已被提议作为阻塞性睡眠呼吸暂停（OSA）未来的药物治疗方法。然而，现有的随机对照试验（RCT）在OSA联合治疗方案的安全性和有效性方面显示出异质性结果。因此，我们对已发表的RCT进行了这项荟萃分析，以澄清这一相互矛盾的证据。
截至2023年12月，对四个电子数据库进行了系统检索。
对13项RCT（n = 345）进行了系统评价和荟萃分析。联合治疗方案显著降低了呼吸暂停低通气指数（AHI）：AHI降低3%[事件/小时；平均差值（MD）：-6.30；95%置信区间（CI）（-9.74，-2.87）；P = 0.0003]，AHI降低4%[事件/小时；MD：-6.50；95%CI（-8.74，-4.26事件/小时）；P < 0.00001]。除平均血氧饱和度外，联合治疗方案组的所有气体测量指标均有显著改善。治疗组和安慰剂组的总睡眠时间无差异。然而，与安慰剂相比，联合治疗方案改变了睡眠结构并降低了睡眠效率。关于OSA的内型，联合治疗方案显著改善了环路增益、咽部肌肉代偿、咽部肌肉募集和呼吸唤醒阈值。
联合治疗方案有效降低了AHI和OSA严重程度，几乎所有OSA内型均有改善。然而，该方案降低了睡眠效率并改变了睡眠结构。短期副作用可能局限于心率加快、口干和排尿犹豫。因此，去甲肾上腺素能药物和抗毒蕈碱药物是一种有前景的OSA治疗方案，但由于该方案缺乏长期效果，这种乐观态度必须有所缓和。建议未来开展关注该方案长期疗效和心血管结局的RCT。
