Acetazolamide as Add-on Diuretic Therapy in Exacerbations of Chronic Heart Failure: a Pilot Study

Abstract

BackgroundCongestion is the main cause of morbidity in patients with heart failure. Treatment of fluid overload is often challenging in everyday clinical practice.ObjectiveThe aim of this study was to determine the diuretic effect of acetazolamide in patients with exacerbations of chronic heart failure, in addition to their stable diuretic therapy.MethodsThis was a single-center, unblinded study. Patients hospitalized with chronic heart failure exacerbations, with left ventricular ejection fraction (EF) < 50% and signs of volume overload, with a stable dose of diuretics anticipated by the attending physician over the next 4 days, were considered eligible for the study. On day 1, patients were randomized to receive acetazolamide orally, once daily (dose-adjusted to body weight) or no treatment (control group) as add-on diuretic therapy, on days 2 and 3. Diuresis, natriuresis, fluid balance, and symptoms were assessed daily, up to day 4.ResultsTwenty patients (mean ± standard deviation age 72 ± 11.6 years; 85% men; mean EF 33.8 ± 11.4%; mean N-terminal pro-B-type natriuretic peptide 8064 ± 5593 pg/mL; mean intravenous furosemide dose 105 ± 55 mg) were enrolled. Diuresis, natriuresis, fluid balance, and symptoms were stable on days 1–4 in the control group. An increase in diuresis and natriuresis, and a greater change in fluid balance after administration of acetazolamide, were observed in patients randomized to acetazolamide. On day 4, there was a significant difference in fluid balance between the acetazolamide and control groups (−666 ± 1194 mL vs. +332 ± 705 mL; p = 0.035), and dyspnea was lower in patients receiving acetazolamide (visual scale, p < 0.001; 5-point Likert scale, 1.444 vs. 2.222; p = 0.04)ConclusionsIn this pilot study, the addition of acetazolamide to the background diuretic regimen in patients with chronic heart failure exacerbations produced an additional diuretic effect and alleviation of dyspnea.

Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance

“…Acetazolamide has been tested in other small prospective studies in AHF. A recent open‐label study randomised 20 AHF patients with ejection fraction < 50% and clinical signs of volume overload to acetazolamide or nothing in addition to usual care . Diuresis, natriuresis, net fluid balance and subjective improvement of dyspnoea were significantly greater in patients receiving acetazolamide.…”

“…However, an observational study in AHF has found that the addition of acetazolamide improves loop diuretic efficiency with approximately 100 mmol sodium excreted in surplus for every 40 mg furosemide‐equivalent dose administered . Other small studies, often before the era of evidence‐based heart failure treatment, corroborate these findings and make acetazolamide an interesting agent to study in combination with loop diuretics for prevention or treatment of diuretic resistance . Acetazolamide blocks sodium bicarbonate reabsorption in the renal proximal tubules, offering more sodium to Henle's loop, hence boosting the effect of loop diuretics, which might be especially useful in states of poor renal blood flow .…”

Use of acetazolamide in the treatment of patients with refractory congestive heart failure

“…However, the experience in daily clinical practice is limited . Verbrugge et al., in a cohort of 54 patients with acute HF and volume overload, found that a combined therapy with acetazolamide was an independent predictor of natriuresis.…”

“…Indeed, the addition of acetazolamide improved loop diuretic efficacy with approximately 100 mg of sodium excretion per 40 mg of furosemide equivalent dose . In other more recent randomized open‐label study that enrolled 20 patients with acute HF and signs of volume overload, the addition of acetazolamide over standard diuretic therapy resulted in some additional effects in parameters of diuretic efficacy and relief of dyspnea …”

“…Acetazolamide, a sulfamide‐derived drug, is and old agent with attractive diuretic properties beyond traditional diuretic strategies in patients with congestive heart failure (CHF) . Its mechanism of action is exerted through the inhibition of the enzyme carbonic anhydrase, leading to a substantial increase in bicarbonate sodium and potassium renal excretion .…”