Acetazolamide Therapy in Patients with Heart Failure: A Meta-Analysis

Background and objectives: Fluid overload and central sleep apnea are highly prevalent in patients with heart failure (HF). We performed this meta-analysis to assess the effects of acetazolamide therapy on acid/base balance and apnea indexes. Methods: A literature search was conducted using EMBASE, MEDLINE, and Cochrane Database from inception through 18 November 2017 to identify studies evaluating the use of acetazolamide in HF. Study results were analyzed using a random effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017065401). Results: Nine studies (three randomized controlled trials and six cohort studies) with a total of 229 HF patients were enrolled. After acetazolamide treatment, there were significant decreases in serum pH (mean difference (MD) of −0.04 (95% CI, −0.06 to −0.02)), pCO2 (MD of −2.06 mmHg (95% CI, −3.60 to −0.53 mmHg)), and serum bicarbonate levels (MD of −6.42 mmol/L (95% CI, −10.05 to −2.79 mmol/L)). When compared to a placebo, acetazolamide significantly increased natriuresis (standardized mean difference (SMD) of 0.67 (95% CI, 0.08 to 1.27)), and decreased the apnea-hypopnea index (AHI) (SMD of −1.06 (95% CI, −1.75 to −0.36)) and central apnea index (CAI) (SMD of −1.10 (95% CI, −1.80 to −0.40)). Egger’s regression asymmetry tests revealed no publication bias with p = 0.20, 0.75 and 0.59 for analysis of the changes in pH, pCO2, and serum bicarbonate levels with use of acetazolamide in HF patients. Conclusion: Our study demonstrates significant reduction in serum pH, increase in natriuresis, and improvements in apnea indexes with use of acetazolamide among HF patients.