EC Pharmacology And Toxicology

Introduction: Acetazolamide is a carbonic anhydrase inhibitor that reduces sodium reabsorption in the renal proximal tubule. It has demonstrated benefit in reducing volume overload in combination with loop diuretics compared to loop monotherapy in acute decompensated heart failure (ADHF) [1]. However, its efficacy and safety compared to the combination of thiazide and loops is unclear.

Objective: To determine whether acetazolamide and loop is superior to thiazide and loop or all three diuretic classes combined in ADHF.

Methods: Retrospective, single-centered, cohort study. Collected data for patients who received intravenous chlorothiazide, oral metolazone, or intravenous acetazolamide from 2021 to 2023. Inclusion criteria was patients aged 18 years or older with ADHF on either loop and thiazide concomitantly or loop and acetazolamide concomitantly. Exclusion criteria was acetazolamide maintenance therapy or extracorporeal membrane oxygenation during hospitalization.

Results: Total 340 patients divided into thiazide and loop (group 1, n = 144), acetazolamide and loop (group 2, n = 105), and all three classes of diuretics (group 3, n = 91). The primary outcome of average net daily urine output was non-significant across all groups before and after adjusting for confounders, including weight, inotrope use, and left ventricular ejection fraction (-1305.0 mL/day vs -1240.0 mL/day vs -1640.0 mL/day, p = 0.223 before adjustment, p = 0.790 and p = 0.321 for group 1 vs 3 and group 2 vs 3 respectively after adjustment). The secondary outcomes, including length of hospital stay, 30-day and 90-day rehospitalization and mortality, and inpatient mortality, were also non-significant.

Conclusion: There is no significant difference in average daily net urine output or safety outcomes among patients treated for ADHF with thiazide and loop, acetazolamide and loop, or all three diuretic classes, even after adjusting for confounders. Further studies are warranted to determine optimal timing and target doses of each diuretic when used in combination.

 Keywords: Cardiology; Heart Failure; Diuretics; Acetazolamide; Acute Decompensated Heart Failure

1. Mullens W., et al. “Acetazolamide in acute decompensated heart failure with volume overload”. New England Journal of Medicine13 (2022): 1185-1195.
2. Heidenreich PA., et al. “2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines”. Circulation18 (2022): e895-e1032.
3. McDonagh TA., et al. “2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure”. European Heart Journal36 (2021): 3599-3726.
4. Konerman MC., et al. “Michigan Medicine Inpatient Diuretic Guideline for Patients with Acute Decompensated Heart Failure”. Ann Arbor (MI): Michigan Medicine University of Michigan (2022).