Oral acetazolamide or thiazide therapy in addition to furosemide for volume control in patients recently discharged with heart failure (ACTHIVOL trial)
B Kalayci, T Altuner, A K G U N Arzu Neslihan, T U G B A Gursoy, B E T U L Akincioglu, E T K I N Elifoglu, B Yigit, A TemizhanAbstract
Background
Acute decompensated heart failure (ADHF) is a major cause of hospitalization and mortality worldwide. Despite standard loop diuretic therapy, maintaining long-term volume control after hospital discharge remains challenging.
Purpose
This prospective, observational study aims to evaluate the effects of adding oral acetazolamide or hydrochlorothiazide to standard oral furosemide therapy on volume maintenance and NT-proBNP levels in patients recently discharged after treatment for ADHF. The primary endpoint is heart failure-related hospitalization, death, and all-cause mortality. Secondaryendpoints include changes in body weight, waist circumference, NT-proBNP, dyspnea score (mMRC score), and NYHA functional class during follow-up.
Methods
Patients hospitalized with acute heart failure, the ADVOR trial demonstrated that the addition of 500 mg intravenous acetazolamide to standard furosemide therapy significantly enhanced decongestion (1). The oral bioavailability ofacetazolamide ranges between 80% and 100%. In a study conducted by Kosirerek, the administration of 250 mg oral acetazolamide in addition to standard furosemide therapy in patients admitted witacute heart failure was associated with increased diuresis and weight loss (2). However, no study has yet investigated the efficacy of oral acetazolamide as and adjunct to standard therapy in patients outside the hospital setting. In this study we aim to evaluate the effects of adding oral acetazolamide to standard oral furosemide therapy on the trajectory of NT-proBNP, congestive symptoms, and urinary spot electrolytes. Patient recruitment for this ethically approved study commenced in December 2025, with a target enrollment of 500 patients. Preliminary results are planned to be presented in May 2026. Eligible patients are adults with known heart failure, hospitalized for ADHF, with NT-proBNP >1000 pg/ml at admission and >30% reduction at discharge, receiving ≥40 mg/day oral furosemide. Exclusion criteria include estimated GFR <30 ml/min/1.73m², de novo heart failure, inadequate NT-proBNP reduction at discharge, chronic steroid use, and comorbid conditions causing non-cardiac volume overload. Patients are followed at outpatient visits during week 1, week 2, and week 4 post-discharge. Long-term outcomes (hospitalization and mortality) are assessed via telephone interviews at 3 months, 6 months, and 1 year, without additional hospital visits.
Conclusion
This ongoing study will provide real-world evidence on the comparative impact of acetazolamide and hydrochlorothiazide as adjuncts to furosemide in maintaining volume control and reducing NT-proBNP levels after ADHF discharge. Findings are expected to clarify whether these strategies improve short- and long-term outcomes, including hospitalization and mortality, in this high-risk patient population.