Acetazolamide as an Adjunctive Diuretic Therapy for Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis

Background Recent evidence suggests that acetazolamide may be beneficial as an adjunctive diuretic therapy in patients with acute decompensated heart failure (HF). We aim to pool all the studies conducted until now and provide updated evidence regarding the role of acetazolamide as adjunctive diuretic in patients with acute decompensated HF. Methods PubMed/Medline, Cochrane Library, and Scopus were searched from inception until July 2023, for randomized and nonrandomized studies evaluating acetazolamide as add-on diuretic in patients with acute decompensated HF. Data about natriuresis, urine output, decongestion, and the clinical signs of congestion were extracted, pooled, and analyzed. Data were pooled using a random effects model. Results were presented as risk ratios (RRs), odds ratios (ORs), or weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Certainty of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) approach. A P value of < 0.05 was considered significant in all cases. Results A total of 5 studies (n = 684 patients) were included with a median follow-up time of 3 months. Pooled analysis demonstrated significantly increased natriuresis (MD 55.07, 95% CI 35.1-77.04, P < 0.00001; I-2 = 54%; moderate certainty), urine output (MD 1.04, 95% CI 0.10-1.97, P = 0.03; I-2 = 79%; moderate certainty) and decongestion [odds ratio (OR) 1.62, 95% CI 1.14-2.31, P = 0.007; I-2 = 0%; high certainty] in the acetazolamide group, as compared with controls. There was no significant difference in ascites (RR 0.56, 95% CI 0.23-1.36, P = 0.20; I-2 = 0%; low certainty), edema (RR 1.02, 95% CI 0.52-2.0, P = 0.95; I-2 = 45%; very low certainty), raised jugular venous pressure (JVP) (RR 0.86, 95% CI 0.63-1.17, P = 0.35; I-2 = 0%; low certainty), and pulmonary rales (RR 0.82, 95% CI 0.44-1.51, P = 0.52; I-2 = 25%; low certainty) between the two groups. Conclusions Acetazolamide as an adjunctive diuretic significantly improves global surrogate endpoints for decongestion therapy but not all individual signs and symptoms of volume overload.