美托洛尔对心力衰竭患者化学感受器反射和中枢性呼吸暂停的影响：一项随机对照交叉试验。

Benefit of buspirone on chemoreflex and central apnoeas in heart failure: a randomized controlled crossover trial.

机构信息

Fondazione Toscana G. Monasterio, Pisa, Italy.

Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.

出版信息

Eur J Heart Fail. 2021 Feb;23(2):312-320. doi: 10.1002/ejhf.1854. Epub 2020 May 22.

DOI:10.1002/ejhf.1854

PMID:32441857

Abstract

AIMS

Increased chemosensitivity to carbon dioxide (CO ) is an important trigger of central apnoeas (CA) in heart failure (HF), with negative impact on outcome. We hypothesized that buspirone, a 5HT receptor agonist that inhibits serotonergic chemoreceptor neuron firing in animals, can decrease CO chemosensitivity and CA in HF.

METHODS AND RESULTS

The BREATH study was a randomized, double-blind, placebo-controlled, crossover study (EudraCT-code 2015-005383-42). Outpatients with systolic HF (left ventricular ejection fraction <50%) and moderate-severe CA [nocturnal apnoea-hypopnoea index (AHI) ≥15 events/h] were randomly assigned to either oral buspirone (15 mg thrice daily) or placebo for 1 week, with a crossover design (1 week of wash-out). The primary effectiveness endpoint was a decrease in CO chemosensitivity >0.5 L/min/mmHg. The primary safety endpoint was freedom from serious adverse events. Sixteen patients (age 71.3 ± 5.8 years, all males, left ventricular ejection fraction 29.8 ± 7.8%) were enrolled. In the intention-to-treat analysis, more patients treated with buspirone (8/16, 50%) had a CO chemosensitivity reduction >0.5 L/min/mmHg from baseline than those treated with placebo (1/16, 6.7%) (difference between groups 43%, 95% confidence interval 14-73%, P = 0.016). Buspirone compared to baseline led to a 41% reduction in CO chemosensitivity (P = 0.001) and to a reduction in the AHI, central apnoea index and oxygen desaturation index of 42%, 79%, 77% at nighttime and 50%, 78%, 86% at daytime (all P < 0.01); no difference was observed after placebo administration (all P > 0.05). No patient reported buspirone-related serious adverse events.

CONCLUSIONS

Buspirone reduces CO chemosensitivity and improves CA and oxygen saturation across the 24 h in patients with HF.

摘要

目的

二氧化碳（CO）化学感受性增加是心力衰竭（HF）中心性呼吸暂停（CA）的重要触发因素，对预后有负面影响。我们假设丁螺环酮，一种 5-羟色胺受体激动剂，可抑制动物中血清素能化学感受器神经元的放电，可降低 HF 中的 CO 化学敏感性和 CA。

方法和结果

BREATH 研究是一项随机、双盲、安慰剂对照、交叉研究（EudraCT 编号 2015-005383-42）。门诊患有收缩性 HF（左心室射血分数 <50%）和中重度 CA[夜间呼吸暂停-低通气指数（AHI）≥15 次/小时]的患者被随机分配接受口服丁螺环酮（15mg 每日 3 次）或安慰剂治疗 1 周，采用交叉设计（1 周洗脱期）。主要有效性终点是 CO 化学敏感性增加>0.5L/min/mmHg。主要安全性终点是无严重不良事件。共纳入 16 名患者（年龄 71.3±5.8 岁，均为男性，左心室射血分数 29.8±7.8%）。在意向治疗分析中，与安慰剂组（1/16，6.7%）相比，更多接受丁螺环酮治疗的患者（8/16，50%）的 CO 化学敏感性从基线下降>0.5L/min/mmHg（组间差异 43%，95%置信区间 14-73%，P=0.016）。与基线相比，丁螺环酮使 CO 化学敏感性降低 41%（P=0.001），并使夜间 AHI、中央呼吸暂停指数和氧减饱和指数分别降低 42%、79%和 77%，白天分别降低 50%、78%和 86%（均 P<0.01）；而安慰剂治疗后无差异（均 P>0.05）。没有患者报告与丁螺环酮相关的严重不良事件。