Efficacy of Oral Acetazolamide as Add-on Diuretic Therapy in Decongestion in Patients with Heart Failure: A Study Protocol for a Randomized Controlled Trial
Abstract
Background: Acute heart failure is a common clinical syndrome leading to hospital admission, with few evidence-based therapies for managing congestion. This trial aims to assess the efficacy of acetazolamide combined with loop diuretics in achieving decongestion among patients who fail to respond to oral diuretics and progress to acute decompensated heart failure in the absence of injectable furosemide.
Methods: This single-center, double-blind randomized controlled trial with a 1:1 allocation ratio aims to evaluate 130 patients admitted to the infusion ward. Participants will receive standard furosemide treatment and be randomized to either oral acetazolamide (250 mg twice daily) or placebo for 3 consecutive days. The primary objective is to assess the efficacy of combined oral acetazolamide and furosemide therapy in achieving decongestion. The prespecified secondary outcomes include the following: N-terminal pro-B-type natriuretic peptide levels on day 30, readmission rates within 3 months, health-related quality of life as assessed by the Heart Failure Quality of Life Questionnaire at 3 months, and changes in weight, creatinine levels, urinary sodium excretion, potassium levels, and hematological indices from the complete blood count on day 3 of the trial.
Conclusion: Diuretic resistance commonly occurs in patients with heart failure, underscoring the urgent need for innovative interventions that can effectively address the limitations of current diuretics, including diuretic resistance and electrolyte imbalances, while enhancing their efficacy in this patient population.
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12. Grodin JL, Simon J, Hachamovitch R, Wu Y, Jackson G, Halkar M, Starling RC, Testani JM, Tang WH. Prognostic Role of Serum Chloride Levels in Acute Decompensated Heart Failure. J Am Coll Cardiol 2015;66:659-666.
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15. Ambrosy AP, Pang PS, Khan S, Konstam MA, Fonarow GC, Traver B, Maggioni AP, Cook T, Swedberg K, Burnett JC Jr, Grinfeld L, Udelson JE, Zannad F, Gheorghiade M; EVEREST Trial Investigators. Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial. Eur Heart J 2013;34:835-843.
16. Naderi N, Bakhshandeh H, Amin A, Taghavi S, Dadashi M, Maleki M. Development and Validation of the First Iranian Questionnaire to Assess Quality of Life in Patients With Heart Failure: IHF-QoL. Res Cardiovasc Med 2012;1:10-16.
17. Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. J Appl Physiol (1985) 2007;1021313-1322.
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19. Katayama F, Miura H, Takanashi S. Long-term effectiveness and side effects of acetazolamide as an adjunct to other anticonvulsants in the treatment of refractory epilepsies. Brain Dev 2002;24:150-154.
20. Saito H, Ogasawara K, Suzuki T, Kuroda H, Kobayashi M, Yoshida K, Kubo Y, Ogawa A. Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion single-photon emission computed tomography in patients with major cerebral artery steno-occlusive diseases. Neurol Med Chir (Tokyo) 2011;51:479-483.
21. Farzam K, Abdullah M. Acetazolamide. [Updated 2023 Jul 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532282/(01 August 2023).
22. Mullens W, Verbrugge FH, Nijst P, Martens P, Tartaglia K, Theunissen E, Bruckers L, Droogne W, Troisfontaines P, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M. Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial. Eur J Heart Fail 2018;20:1591-1600.
23. Mullens W, Dauw J, Martens P, Meekers E, Nijst P, Verbrugge FH, Chenot F, Moubayed S, Dierckx R, Blouard P, Derthoo D, Smolders W, Ector B, Hulselmans M, Lochy S, Raes D, Van Craenenbroeck E, Vandekerckhove H, Hofkens PJ, Goossens K, Pouleur AC, De Ceuninck M, Gabriel L, Timmermans P, Prihadi EA, Van Durme F, Depauw M, Vervloet D, Viaene E, Vachiery JL, Tartaglia K, Ter Maaten JM, Bruckers L, Droogne W, Troisfontaines P, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M. Acetazolamide in Decompensated Heart Failure with Volume Overload trial (ADVOR): baseline characteristics. Eur J Heart Fail 2022;24:1601-1610.
24. Verbrugge FH, Dupont M, Bertrand PB, Nijst P, Penders J, Dens J, Verhaert D, Vandervoort P, Tang WH, Mullens W. Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload. Acta Cardiol 2015;70:265-273.
25. Kataoka H. Acetazolamide as a potent chloride-regaining diuretic: short- and long-term effects, and its pharmacologic role under the 'chloride theory' for heart failure pathophysiology. Heart Vessels 2019;34:1952-1960.
2. Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC, Coats AJS. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res 2023;118:3272-3287.
3. Rogers C, Bush N. Heart Failure: Pathophysiology, Diagnosis, Medical Treatment Guidelines, and Nursing Management. Nurs Clin North Am 2015;50:787-799.
4. Sinnenberg L, Givertz MM. Acute heart failure. Trends Cardiovasc Med 2020;30:104-112.
5. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, Ford E, Furie K, Go A, Greenlund K, Haase N, Hailpern S, Ho M, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott M, Meigs J, Mozaffarian D, Nichol G, O'Donnell C, Roger V, Rosamond W, Sacco R, Sorlie P, Stafford R, Steinberger J, Thom T, Wasserthiel-Smoller S, Wong N, Wylie-Rosett J, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:e21-181.
6. Wongboonsin J, Thongprayoon C, Bathini T, Ungprasert P, Aeddula NR, Mao MA, Cheungpasitporn W. Acetazolamide Therapy in Patients with Heart Failure: A Meta-Analysis. J Clin Med 2019;8:349.
7. Verbrugge FH, Martens P, Ameloot K, Haemels V, Penders J, Dupont M, Tang WHW, Droogné W, Mullens W. Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance. Eur J Heart Fail 2019;21:1415-1422.
8. Imiela T, Budaj A. Acetazolamide as Add-on Diuretic Therapy in Exacerbations of Chronic Heart
9. Rivera FB, Alfonso P, Golbin JM, Lo K, Lerma E, Volgman AS, Kazory A. The Role of Serum Chloride in Acute and Chronic Heart Failure: A Narrative Review. Cardiorenal Med 2021;11:87-98.
10. Zandijk AJL, van Norel MR, Julius FEC, Sepehrvand N, Pannu N, McAlister FA, Voors AA, Ezekowitz JA. Chloride in Heart Failure: The Neglected Electrolyte. JACC Heart Fail 2021;9:904-915.
11. Kataoka H. Treatment of hypochloremia with acetazolamide in an advanced heart failure patient and importance of monitoring urinary electrolytes. J Cardiol Cases 2017;17:80-84.
12. Grodin JL, Simon J, Hachamovitch R, Wu Y, Jackson G, Halkar M, Starling RC, Testani JM, Tang WH. Prognostic Role of Serum Chloride Levels in Acute Decompensated Heart Failure. J Am Coll Cardiol 2015;66:659-666.
13. Kalra PR, Anagnostopoulos C, Bolger AP, Coats AJ, Anker SD. The regulation and measurement of plasma volume in heart failure. J Am Coll Cardiol 2002;39:1901-1908.
14. Cody RJ, Covit AB, Schaer GL, Laragh JH, Sealey JE, Feldschuh J. Sodium and water balance in chronic congestive heart failure. J Clin Invest 1986;77:1441-1452.
15. Ambrosy AP, Pang PS, Khan S, Konstam MA, Fonarow GC, Traver B, Maggioni AP, Cook T, Swedberg K, Burnett JC Jr, Grinfeld L, Udelson JE, Zannad F, Gheorghiade M; EVEREST Trial Investigators. Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial. Eur Heart J 2013;34:835-843.
16. Naderi N, Bakhshandeh H, Amin A, Taghavi S, Dadashi M, Maleki M. Development and Validation of the First Iranian Questionnaire to Assess Quality of Life in Patients With Heart Failure: IHF-QoL. Res Cardiovasc Med 2012;1:10-16.
17. Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. J Appl Physiol (1985) 2007;1021313-1322.
18. Low EV, Avery AJ, Gupta V, Schedlbauer A, Grocott MP. Identifying the lowest effective dose of acetazolamide for the prophylaxis of acute mountain sickness: systematic review and meta-analysis. BMJ 2012;345:e6779.
19. Katayama F, Miura H, Takanashi S. Long-term effectiveness and side effects of acetazolamide as an adjunct to other anticonvulsants in the treatment of refractory epilepsies. Brain Dev 2002;24:150-154.
20. Saito H, Ogasawara K, Suzuki T, Kuroda H, Kobayashi M, Yoshida K, Kubo Y, Ogawa A. Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion single-photon emission computed tomography in patients with major cerebral artery steno-occlusive diseases. Neurol Med Chir (Tokyo) 2011;51:479-483.
21. Farzam K, Abdullah M. Acetazolamide. [Updated 2023 Jul 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532282/(01 August 2023).
22. Mullens W, Verbrugge FH, Nijst P, Martens P, Tartaglia K, Theunissen E, Bruckers L, Droogne W, Troisfontaines P, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M. Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial. Eur J Heart Fail 2018;20:1591-1600.
23. Mullens W, Dauw J, Martens P, Meekers E, Nijst P, Verbrugge FH, Chenot F, Moubayed S, Dierckx R, Blouard P, Derthoo D, Smolders W, Ector B, Hulselmans M, Lochy S, Raes D, Van Craenenbroeck E, Vandekerckhove H, Hofkens PJ, Goossens K, Pouleur AC, De Ceuninck M, Gabriel L, Timmermans P, Prihadi EA, Van Durme F, Depauw M, Vervloet D, Viaene E, Vachiery JL, Tartaglia K, Ter Maaten JM, Bruckers L, Droogne W, Troisfontaines P, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M. Acetazolamide in Decompensated Heart Failure with Volume Overload trial (ADVOR): baseline characteristics. Eur J Heart Fail 2022;24:1601-1610.
24. Verbrugge FH, Dupont M, Bertrand PB, Nijst P, Penders J, Dens J, Verhaert D, Vandervoort P, Tang WH, Mullens W. Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload. Acta Cardiol 2015;70:265-273.
25. Kataoka H. Acetazolamide as a potent chloride-regaining diuretic: short- and long-term effects, and its pharmacologic role under the 'chloride theory' for heart failure pathophysiology. Heart Vessels 2019;34:1952-1960.
| Files | ||
| Issue | Vol 19 No 1 (2024): J Teh Univ Heart Ctr | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jthc.v19i1.15537 | |
| Keywords | ||
| Acetazolamide Heart failure Diuretics Chloride Decongestion | ||
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How to Cite
1.
Bavandpour Karvane H, Ashraf H, Aghakouchakzadeh M, Navid H, Bozorgi A. Efficacy of Oral Acetazolamide as Add-on Diuretic Therapy in Decongestion in Patients with Heart Failure: A Study Protocol for a Randomized Controlled Trial. J Tehran Heart Cent. 2024;19(1):47-53.
