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

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Abstract

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; I2 = 54%; moderate certainty), urine output (MD 1.04, 95% CI 0.10–1.97, P = 0.03; I2 = 79%; moderate certainty) and decongestion [odds ratio (OR) 1.62, 95% CI 1.14–2.31, P = 0.007; I2 = 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; I2 = 0%; low certainty), edema (RR 1.02, 95% CI 0.52–2.0, P = 0.95; I2 = 45%; very low certainty), raised jugular venous pressure (JVP) (RR 0.86, 95% CI 0.63–1.17, P = 0.35; I2 = 0%; low certainty), and pulmonary rales (RR 0.82, 95% CI 0.44–1.51, P = 0.52; I2 = 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.

Systematic Review Registration

This systematic review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), registration number CRD498330.

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Authors and Affiliations

  1. Department of Medicine, Ziauddin Medical University, Karachi, Pakistan

    Ahmed Kamal Siddiqi & Muhammad Talha Maniya

  2. Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan

    Muhammad Tanveer Alam

  3. Department of Cardiology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA

    Andrew P. Ambrosy

  4. Kaiser Permanente Northern California Division of Research, Oakland, CA, USA

    Andrew P. Ambrosy

  5. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Marat Fudim & Stephen J. Greene

  6. Duke Clinical Research Institute, Durham, NC, USA

    Marat Fudim & Stephen J. Greene

  7. Division of Cardiology, Duke University School of Medicine, Duke University Medical Center, 2301 Erwin Rd., Durham, NC, 27705, USA

    Marat Fudim, Stephen J. Greene & Muhammad Shahzeb Khan

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A.P.A. is supported by a grant from the National Heart, Lung, and Blood Institute (K23HL150159), American Heart Association (no. 1155554), has received relevant research support through grants to his institution from Amarin Pharma, Inc., Abbott, and Novartis, and modest reimbursement for travel from Novartis. Dr. Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association (no. 929502), Amgen, AstraZeneca, Boehinger Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards or as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/ Lilly, Bristol Myers Squibb, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Lexicon, Merck, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. M.F. is supported by the Mario Family Award, Duke Chair’s Award, Translating Duke Health Award, Bayer, and BTG Specialty Pharmaceuticals. He receives consulting fees from AxonTherapies, Bodyport, CVRx, Daxor, Edwards LifeSciences, Fire1, NXT Biomedical, Zoll, and Viscardia. S.J.G. has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association (no. 929502), National Heart Lung and Blood Institute, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim/ Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, Sanofi, and scPharmaceuticals; serves as a consultant for Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim/ Lilly, CSL Vifor, Merck, PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim and Cytokinetics.

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Siddiqi, A.K., Maniya, M.T., Alam, M.T. et al. Acetazolamide as an Adjunctive Diuretic Therapy for Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs 24, 273–284 (2024). https://doi.org/10.1007/s40256-024-00633-9

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