2026 Southeastern Residency Conference

TITLE: Comparative Effectiveness of Acetazolamide Versus Thiazide-like Diuretics for Sequential Nephron Blockade in Acute Decompensated Heart Failure: A Retrospective Cohort Study

AUTHORS: Angel D. Posadas, Otsanya Ochogbu

BACKGROUND: Intravenous loop diuretics are recommended as first-line therapy for the management of volume overload in acute decompensated heart failure (ADHF); however, many patients experience an inadequate diuretic response, resulting in persistent congestion. Sequential nephron blockade with thiazide-like diuretics or acetazolamide is commonly used to enhance diuresis in patients with diuretic resistance. Traditionally, thiazide-like diuretics have been used as add-on therapy when response to loop diuretics is insufficient. More recently, acetazolamide, a carbonic anhydrase inhibitor, has gained interest as an alternative strategy as studies have shown improved decongestion when compared to placebo. This study aimed to compare the effectiveness and safety of acetazolamide versus thiazide-like diuretics when combined with loop diuretics in adult patients hospitalized with ADHF.

METHODS: A single-center retrospective observational cohort study was conducted at AdventHealth Orlando evaluating adult patients hospitalized with ADHF between January 1, 2023 and January 1, 2025. Patients 18 years or older who received intravenous loop diuretics and adjunctive diuresis with either acetazolamide or a thiazide-like diuretic (metolazone or chlorothiazide) during hospitalization were included. Patients were excluded if they were on acetazolamide or a thiazide-like diuretic prior to admission, on extracorporeal membrane oxygenation, had end-stage renal disease, estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m², or concomitant use of both adjunctive agents. The primary endpoint was average daily net fluid balance assessed for up to 72 hours of adjunctive diuretics. Secondary endpoints included net fluid balance at 24, 48, and 72 hours, change in body weight, hospital length of stay, inpatient mortality, 30-day readmission, and adverse events including hypokalemia, acute kidney injury (AKI), and arrhythmias.

RESULTS: A total of 897 patients were screened and 711 were excluded, primarily due to receipt of both adjunctive agents or lack of concomitant use with intravenous loop diuretics. A total of 186 patients were included in the study, 80 who received acetazolamide and 106 who received a thiazide-like diuretic. Baseline characteristics were generally similar between groups; however, patients receiving thiazides had higher baseline serum creatinine, and higher prevalence of chronic kidney disease (CKD). Baseline loop diuretic dose prior to adjunctive therapy was similar between groups (60 mg vs 80 mg; p=0.177). Median duration of adjunctive therapy was longer in the acetazolamide group compared to the thiazide group (2 vs 1 days; p =0.027). There was no difference in the average daily net fluid balance in patients receiving acetazolamide as compared to thiazides (−1634.9 mL/day vs −1553.0 mL/day; p=0.791). There was also no difference in the net fluid balance at 24, 48, and 72 hours between acetazolamide and thiazide groups. Patients receiving acetazolamide had significant weight reduction from admission to discontinuation of the adjunctive agent (−5.56 ± 6.75 kg vs −2.66 ± 6.05 kg; p=0.027) and a longer hospital length of stay (15 days vs 12.5 days; p=0.016). There was no difference in the incidence of inpatient mortality (6.3% vs 11.3%; p=0.235), 30-day readmission (20.0% vs 22.3%; p=0.712), hypokalemia (21.3% vs 23.6%; p=0.706), and arrhythmias (1.9% vs 2.5%; p=1.000). There was a significantly lower incidence of AKI in patients treated with acetazolamide compared with thiazides (20.0% vs 58.5%; p<0.001).

CONCLUSION: There was no difference in net fluid balance in patients treated with acetazolamide as compared to thiazide-like diuretics in patients admitted with ADHF, however, acetazolamide was associated with greater weight reduction. While a lower incidence of AKI was observed with acetazolamide, the higher prevalence of CKD in the thiazide group may have confounded this finding. Overall, these results suggest comparable diuretic efficacy between both agents, but larger randomized controlled trials are needed to evaluate differences in clinical outcomes and safety.