"Acetazolamide in Patients with Acute Decompensated Heart Failure with Volume Overload".The New England Journal of Medicine. 2023.

Clinical Question

Does the addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure result in improved decongestion?

Bottom Line

Adding acetazolamide to loop diuretic therapy in acute decompensated heart failure patients with volume overload led to a more successful decongestion within 3 days of treatment, as well as a more pronounced reduction in congestion symptoms, with similar safety profiles observed between acetazolamide and placebo groups.

Major Points

Guidelines

Current guidelines recommend intravenous loop diuretics for symptom relief from fluid overload in patients with acute decompensated heart failure; however, there is limited evidence on effective adjunctive diuretic therapy.

Design

- Multicenter, parallel-group, double-blind, randomized, placebo-controlled trial
- N=519 patients with acute decompensated heart failure
- Acetazolamide 500mg IV once daily (n=259)
- Placebo (n=260)
- Setting: 27 centers in Belgium
- Enrollment: 2018-2022
- Follow-up: 3 months
- Analysis: Intention-to-treat
- Primary outcome: Successful decongestion within 3 days of treatment

Population

- Inclusion Criteria: Adults with acute decompensated heart failure and signs of volume overload (edema, pleural effusion, or ascites), NT-proBNP >1000 pg/ml or BNP >250 pg/ml, prior loop diuretic maintenance for ≥1 month
- Exclusion Criteria: Use of acetazolamide or another proximal tubular diuretic (e.g. SGLT2 inhibitors), systolic BP <90 mm Hg, estimated GFR <20 ml/min/1.73 m^2, IV loop diuretics >80 mg furosemide equivalent prior to randomization

Interventions

- Acetazolamide 500 mg IV or placebo added to standardized IV loop diuretics (dose equivalent to twice the oral maintenance dose) once daily
- Oral loop diuretics were discontinued during the trial period

Outcomes

- Primary: Successful decongestion within 3 days of randomization without escalation of decongestive therapy
- Secondary: Composite of death from any cause or rehospitalization for heart failure during 3 months

Criticisms

- Majority of trial participants were White, limiting generalizability to other racial or ethnic groups.
- The study population had chronic heart failure history and were on outpatient treatment with loop diuretics, which may not apply to newly diagnosed heart failure patients.

Funding

The trial was funded by the Belgian Health Care Knowledge Center.

Further Reading