Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular disease: A randomized, double-blind, cross-over trial

IF 10.4 2区 医学 Q1 RESPIRATORY SYSTEM
M. Lichtblau , S. Saxer , J. Müller , P. Appenzeller , C. Berlier , S.R. Schneider , L. Mayer , M. Furian , E.I. Schwarz , E.R. Swenson , K.E. Bloch , S. Ulrich
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引用次数: 0

Abstract

Background

The carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown.

Methods

28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.6±15.0 years stable on PVD medications, were randomised in a double-blind crossover protocol to 5 weeks acetazolamide (250mg b.i.d) or placebo separated by a ≥2 week washout period. Primary endpoint was the change in 6-minute walk distance (6MWD) at 5 weeks. Additional endpoints included safety, tolerability, WHO functional class, quality of life, arterial blood gases, and hemodynamics (by echocardiography).

Results

Acetazolamide had no effect on 6MWD compared to placebo (treatment effect: mean change [95%CI] -18 [-40 to 4]m, p=0.102) but increased arterial blood oxygenation through hyperventilation induced by metabolic acidosis. Other measures including pulmonary hemodynamics were unchanged. No severe adverse effects occurred, side effects that occurred significantly more frequently with acetazolamide vs. placebo were change in taste (22/0%), paraesthesia (37/4%) and mild dyspnea (26/4%).

Conclusions

In patients with PVD, acetazolamide did not change 6MWD compared to placebo despite improved blood oxygenation. Some patients reported a tolerable increase in dyspnoea during acetazolamide treatment, related to hyperventilation, induced by the mild drug-induced metabolic acidosis. Our findings do not support the use of acetazolamide to improve exercise in patients with PVD at this dosing.

ClinicalTrials.gov Identifier

NCT02755298

口服乙酰唑胺 5 周对肺血管疾病患者的影响:随机、双盲、交叉试验。
背景:碳酸酐酶抑制剂乙酰唑胺通过肾脏碳酸氢盐排泄介导的代谢性酸中毒刺激通气。在动物模型中,乙酰唑胺可减轻急性缺氧诱发的肺动脉高压(PH),但其对因肺血管疾病(PVD)导致的肺动脉高压患者的治疗效果尚不清楚。方法:28名PVD患者(15名肺动脉高压患者,13名远端慢性血栓栓塞性PH患者),13名女性,平均(±SD)年龄为61.6±15.0岁,稳定服用PVD药物,在双盲交叉方案中随机接受为期5周的乙酰唑胺(250毫克,b.i.d)或安慰剂治疗,中间有≥2周的冲洗期。主要终点是5周时6分钟步行距离(6MWD)的变化。其他终点包括安全性、耐受性、WHO功能分级、生活质量、动脉血气和血液动力学(通过超声心动图):与安慰剂相比,乙酰唑胺对6MWD没有影响(治疗效果:平均变化[95%CI] -18 [-40 to 4]米,P=0.102),但通过代谢性酸中毒引起的过度通气增加了动脉血氧饱和度。包括肺血液动力学在内的其他指标均无变化。与安慰剂相比,乙酰唑胺无严重不良反应,但出现频率明显高于安慰剂的副作用有味觉改变(22/0%)、麻痹(37/4%)和轻度呼吸困难(26/4%):尽管改善了血氧饱和度,但与安慰剂相比,乙酰脞胺并未改变心血管疾病患者的6MWD。一些患者表示,在乙酰唑胺治疗期间,呼吸困难的增加是可以忍受的,这与药物引起的轻度代谢性酸中毒导致的过度换气有关。我们的研究结果不支持在此剂量下使用乙酰唑胺来改善心血管疾病患者的运动状况:Gov 标识符:NCT02755298。
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来源期刊
Pulmonology
Pulmonology Medicine-Pulmonary and Respiratory Medicine
CiteScore
14.30
自引率
5.10%
发文量
159
审稿时长
19 days
期刊介绍: Pulmonology (previously Revista Portuguesa de Pneumologia) is the official journal of the Portuguese Society of Pulmonology (Sociedade Portuguesa de Pneumologia/SPP). The journal publishes 6 issues per year and focuses on respiratory system diseases in adults and clinical research. It accepts various types of articles including peer-reviewed original articles, review articles, editorials, and opinion articles. The journal is published in English and is freely accessible through its website, as well as Medline and other databases. It is indexed in Science Citation Index Expanded, Journal of Citation Reports, Index Medicus/MEDLINE, Scopus, and EMBASE/Excerpta Medica.
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