Effects of 5-Week Oral Acetazolamide on Incremental Cycling Exercise in Pulmonary Arterial and Chronic Thromboembolic Pulmonary Hypertension: A Randomized Placebo-Controlled, Double-Blinded, Crossover Trial

Abstract

Introduction: Acetazolamide (AZA) improves nocturnal and daytime blood oxygenation in patients with pulmonary vascular disease (PVD), defined as pulmonary arterial and distal chronic thromboembolic pulmonary hypertension (CTEPH), and may improve exercise performance. Methods: We investigated the effect of 5 weeks of AZA (250 mg bid) versus placebo on maximal load during incremental cycling ramp exercise in patients with PVD studied in a randomized controlled, double-blind, crossover design, separated by > 2 weeks of washout. Results: Twenty-five patients (12 pulmonary arterial hypertension, 13 CTEPH, 40% women, age 62 ± 15 years) completed the trial according to the protocol. Maximum load was similar after 5 weeks of AZA versus placebo (113 ± 9 vs. 117 ± 9 watts [W]), mean difference −4 W (95% CI: −9 to 1, p = 0.138). With AZA, maximum (max)-exercise partial pressure of O₂ (PaO₂) was significantly higher by 1.1 kPa (95% CI: 0.5–1.8, p = 0.003), while arterial pH and partial pressure of CO₂ were significantly lower. Gas exchange threshold was reached at a higher load with AZA (108 ± 8 W vs. 97 ± 8 W) and was therefore delayed by 11 W (95% CI: 3–19, p = 0.013), while the ventilatory equivalent for O₂ and CO₂ were significantly higher at both the max-exercise and gas exchange threshold with AZA versus placebo. Conclusion: AZA for 5 weeks did not significantly change maximum exercise capacity in patients with PVD despite a significant increase in PaO₂. The beneficial effects of increased blood oxygenation may have been diminished by increased ventilation due to AZA-induced metabolic acidosis and increased dyspnea.