"Acetazolamide in Patients with Acute Decompensated Heart Failure with Volume Overload".The New England Journal of Medicine. 2023.
Links to original sources: Wiki Journal Post Full Journal Article
Does the addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure result in improved decongestion?
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.
Intravenous loop diuretics are routinely used for symptomatic management in patients with acute decompensated heart failure, but many patients are still discharged from the hospital with residual signs of volume overload, which has been associated with worse outcomes. The ADVOR trial evaluated the efficacy of acetazolamide, a carbonic anhydrase inhibitor that decreases proximal tubular sodium reabsorption as an adjunct to loop diuretics, in achieving improved and faster decongestion.
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.
- 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
- 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
- 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
- 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
- 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.
The trial was funded by the Belgian Health Care Knowledge Center.
The NEJM publication and supplementary material for the ADVOR trial.