From the Guidelines
The ADVOR trial is the most relevant study examining the use of acetazolamide during diuretic therapy for Heart Failure (HF) exacerbations, and its protocol involved administering acetazolamide for 72 hours on top of standard of care. The study found that acetazolamide resulted in more efficient decongestion, but this did not affect all-cause mortality and HF rehospitalizations 1. The protocol of the ADVOR trial is crucial in understanding the potential benefits and risks of using acetazolamide in this context. Some key points about the protocol include:
- Acetazolamide was administered for 72 hours on top of standard of care
- The study aimed to assess the effect of acetazolamide on decongestion in patients with decompensated heart failure and volume overload
- The results showed that acetazolamide doubled the incidence of transient worsening of renal function during hospital stay, but mean creatinine at 3 months did not differ between the study arms 1 The use of acetazolamide in this context is supported by its mechanism of action, which involves inhibiting carbonic anhydrase in the proximal tubule, preventing sodium reabsorption, and enhancing natriuresis when combined with loop diuretics. Key considerations for clinicians include:
- The potential benefits of acetazolamide in improving decongestion rates
- The potential risks, including transient worsening of renal function
- The need for careful patient selection and monitoring when using acetazolamide in this context 1
From the FDA Drug Label
The use of acetazolamide does not eliminate the need for other therapy such as digitalis, bed rest, and salt restriction. For diuresis in congestive heart failure, the starting dose is usually 250 to 375 mg once daily in the morning (5 mg/kg) If, after an initial response, the patient fails to continue to lose edema fluid, do not increase the dose but allow for kidney recovery by skipping medication for a day. Acetazolamide yields best diuretic results when given on alternate days, or for two days alternating with a day of rest.
The study that examined the use of acetazolamide during diuretic therapy for Heart Failure (HF) exacerbations is not specified in the provided text. The protocol for using acetazolamide in congestive heart failure is to start with a dose of 250 to 375 mg once daily in the morning, and to allow for kidney recovery by skipping medication for a day if the patient fails to continue to lose edema fluid after an initial response. Acetazolamide yields best diuretic results when given on alternate days, or for two days alternating with a day of rest 2.
From the Research
Study Examination
The study that examined the use of acetazolamide during diuretic therapy for Heart Failure (HF) exacerbations is the ADVOR trial 3.
Protocol
The protocol involved randomizing 519 patients with ADHF to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics.
Key Findings
- Acetazolamide consistently increased the likelihood of decongestion across the entire spectrum of eGFR (P-interaction = .977) 3.
- Natriuresis and diuresis were higher with acetazolamide, with a higher treatment effect for patients with low eGFR (both P-interaction < .007) 3.
- Acetazolamide was associated with a higher incidence of worsening renal function (WRF; rise in creatinine ≥ 0.3 mg/dL) during the treatment period (40.5% vs. 18.9%; P < .001) 3.
Other Studies
Other studies also investigated the use of acetazolamide in HF management, including:
- A literature review that analyzed six studies evaluating the effectiveness of acetazolamide as an additive treatment for acute decompensated heart failure (ADHF) 4.
- A single-center, prospective, randomized study that assessed the decongestive, natriuretic, and chloride-regaining effects of oral acetazolamide as an add-on therapy for acute heart failure with volume overload 5.
- A case report that presented a patient with improved urine output after receiving acetazolamide, highlighting its potential role in diuretic resistance 6.
- A multicenter, retrospective cohort study that compared the use of intravenous (IV) and oral (PO) acetazolamide for patients with HF receiving at least 120 mg of furosemide for the treatment of metabolic alkalosis 7.