Acetazolamide Reduces Blood Pressure and Sleep-Disordered Breathing in Patients With Hypertension and Obstructive Sleep Apnea: A Randomized Controlled Trial

Abstract

Study objectives: The carbonic anhydrase inhibitor acetazolamide (AZT) modulates blood pressure at high altitude and reduces sleep-disordered breathing in patients with obstructive sleep apnea (OSA). We aimed to investigate the treatment effect of AZT and in combination with continuous positive airway pressure (CPAP) on blood pressure in patients with hypertension and OSA.

Methods: In a prospective, randomized, three-way crossover study, 13 male patients with hypertension and moderate to severe OSA (age 64 ± 7 years, body mass index 29 ± 4 kg/m2, and mean apnea-hypopnea index 37 ± 23 events/h) received AZT, CPAP, or AZT plus CPAP for 2-week periods. Antihypertensive medication was washed out. Office and 24-hour blood pressure, arterial stiffness, polygraphic sleep study data, and blood chemistry were compared.

Results: AZT alone and AZT plus CPAP, but not CPAP alone, reduced office mean arterial pressure compared to baseline (-7 [95% CI -11 to -4], -7 [95% CI -11 to -4] and -1 [95% CI -5 to 4] mmHg, respectively; repeated- measures analysis of variance (RM-ANOVA; P = .015). Aortic systolic pressure and augmentation index, assessed by radial artery oscillatory tonometry, were unaffected by CPAP but decreased after AZT and AZT plus CPAP (RM-ANOVA P = .030 and .031, respectively). The apnea-hypopnea index was significantly reduced in all three treatment arms, most prominently by AZT plus CPAP (RM-ANOVA P = .003). The reduction of venous bicarbonate concentration following AZT was correlated with the change of apnea-hypopnea index (r = 0.66, P = .013).

Conclusions: AZT reduced blood pressure, vascular stiffness, and sleep-disordered breathing in patients with OSA and comorbid hypertension. Carbonic anhydrase inhibition may constitute a potential target for drug therapy in patients with sleep apnea and comorbid hypertension.

Clinical trial registration: Registry: ClinicalTrials.gov; Identifier: NCT02220803; Title: A Short Term Open, Randomized Cross-over Trial Exploring the Effect of Carbonic Anhydrase Inhibition by Acetazolamide on Sleep Apnea Associated Hypertension and Vascular Dysfunction; URL: https://ichgcp.net/clinical-trials-registry/NCT02220803 and Registry: EU Clinical Trials Register; EudraCT Number: 2013-004866-33; Title: A short term open, randomized cross over trial exploring the effect of carbonic anhydrase inhibition by acetazolamide on sleep apnea associated hypertension; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004866-33.

Keywords: blood pressure; carbonic anhydrase; hypertension; obstructive sleep apnea; pharmacotherapy; randomized controlled trial; treatment.

© 2018 American Academy of Sleep Medicine.

Figures

Figure 1. Study flow chart.

AZT = acetazolamide, CPAP = continuous positive airway pressure.

Figure 2. Hemodynamic changes following CPAP, acetazolamide, and acetazolamide plus CPAP treatments.

Individual data of office mean arterial pressure (top panels) and aortic augmentation index (bottom panels) at baseline and follow-up in the CPAP, acetazolamide, and acetazolamide plus CPAP groups. Mean values at baseline and follow-up are indicated by the solid black bars. Significance values refer to comparison within groups. CPAP = continuous positive airway pressure.

Figure 3. Reduction in AHI.

Mean unadjusted (white bars) and adherence-adjusted (gray bars) reduction in CPAP and acetazolamide groups. Shown is mean change of reduction in AHI and 95% confidence interval. AHI = apnea-hypopnea index, CPAP = continuous positive airway pressure, NS = nonsignificant.

Figure 4. Spearman correlation between change in venous standard bicarbonate concentration and change in AHI.

AHI = apnea-hypopnea index.