PMID- 36639329
OWN - NLM
STAT- Publisher
LR  - 20240216
IS  - 2531-0437 (Electronic)
IS  - 2531-0429 (Linking)
DP  - 2023 Jan 11
TI  - Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular 
      disease: A randomized, double-blind, cross-over trial.
LID - S2531-0437(22)00262-8 [pii]
LID - 10.1016/j.pulmoe.2022.11.004 [doi]
AB  - 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. GOV 
      IDENTIFIER: NCT02755298.
CI  - Copyright (c) 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier 
      Espana, S.L.U. All rights reserved.
FAU - Lichtblau, M
AU  - Lichtblau M
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
FAU - Saxer, S
AU  - Saxer S
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
FAU - Muller, J
AU  - Muller J
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
FAU - Appenzeller, P
AU  - Appenzeller P
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
FAU - Berlier, C
AU  - Berlier C
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
FAU - Schneider, S R
AU  - Schneider SR
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
FAU - Mayer, L
AU  - Mayer L
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
FAU - Furian, M
AU  - Furian M
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
FAU - Schwarz, E I
AU  - Schwarz EI
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
FAU - Swenson, E R
AU  - Swenson ER
AD  - Division of Pulmonary, Critical Care and Sleep Medicine, VA Puget Sound Health 
      Care System, University of Washington, Seattle, Washington, USA.
FAU - Bloch, K E
AU  - Bloch KE
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland; 
      Center for Human Integrative Physiology, and Zurich Center for Interdisciplinary 
      Sleep Research, University of Zurich, Switzerland.
FAU - Ulrich, S
AU  - Ulrich S
AD  - Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland; 
      Center for Human Integrative Physiology, and Zurich Center for Interdisciplinary 
      Sleep Research, University of Zurich, Switzerland. Electronic address: 
      silvia.ulrich@usz.ch.
LA  - eng
SI  - ClinicalTrials.gov/NCT02755298
PT  - Journal Article
DEP - 20230111
PL  - Spain
TA  - Pulmonology
JT  - Pulmonology
JID - 101723786
SB  - IM
OTO - NOTNLM
OT  - 6-Minute walk distance
OT  - Acetazolamide
OT  - Chronic thromboembolic pulmonary hypertension
OT  - Exercise capacity
OT  - Pulmonary arterial hypertension
OT  - Pulmonary vascular disease
COIS- Conflicts of interest None of the authors report any conflict of interest in 
      direct relation to this manuscript. Prof. Dr. med. S. Ulrich reports grants from 
      Johnson and Johnson SA, Switzerland, during the conduct of the study; grants from 
      Zurich Lung, grants from Orpha Swiss, personal fees from Actelion SA, 
      Switzerland, personal fees from MSD Switzerland, outside the submitted work. Dr. 
      Swenson reports that he has a patent: METHODS OF TREATING PULMONARY DISEASE USING 
      ACETAZOLAMIDE AND STRUCTURALLY RELATED DERIVATIVES issued by the US government 
      with the the patent designation US Patent No. 8,614,236
EDAT- 2023/01/14 06:00
MHDA- 2023/01/14 06:00
CRDT- 2023/01/13 22:05
PHST- 2022/08/18 00:00 [received]
PHST- 2022/11/08 00:00 [revised]
PHST- 2022/11/08 00:00 [accepted]
PHST- 2023/01/13 22:05 [entrez]
PHST- 2023/01/14 06:00 [pubmed]
PHST- 2023/01/14 06:00 [medline]
AID - S2531-0437(22)00262-8 [pii]
AID - 10.1016/j.pulmoe.2022.11.004 [doi]
PST - aheadofprint
SO  - Pulmonology. 2023 Jan 11:S2531-0437(22)00262-8. doi: 
      10.1016/j.pulmoe.2022.11.004.