Congestive heart failure diuretics

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2] Edzel Lorraine Co, DMD, MD[3]

## Overview

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Diuretics reduce circulating volume, improve symptoms and are a mainstay of therapy for congestive heart failure. While these agents improve symptoms, they have not been associated with a reduction in mortality and are associated with electrolyte imbalances.

## Diuretics

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### Diuretics

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* Loop diuretics is recommended to reduce the signs and/or symptoms of congestion in patients with HFrEF.[1]
* The effects of diuretics on morbidity and mortality have not been studied in RCTs.
* Loop diuretics and thiazide diuretics appear to reduce the risk of death and worsening HF compared with a placebo.
* Diuretics can improve exercise capacity.[2]
* Loop diuretics and thiazides act synergistically and may be used to treat diuretic resistance.
* ARNI, MRAs, and SGLT2 inhibitors may also possess diuretic properties.
* Maintaining the euvolemia state is the aim of diuretic therapy with the lowest doses.[3]
* Patients should be trained to self-adjust their diuretic dose based on monitoring of symptoms/signs of congestion and daily weight measurements.

### MRA or Mineralocorticoid receptor antagonists

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* In all patients with HFrEF, MRAs (spironolactone or eplerenone) are recommended, in addition to an ACE-I and a beta-blocker, to reduce mortality and the risk of heart failure hospitalization.[4]
* MRAs improve symptoms.
* MRAs block receptors that bind aldosterone and also other steroid hormones (corticosteroid and androgen) receptors.
* Eplerenone is more specific for aldosterone blockade and, therefore, causes less gynaecomastia.
* In patients with impaired renal function and in those with serum potassium concentrations >5.0 mmol/L, MRA should be used with causion.

## 2022 AHA/ACC/HFSA Heart Failure Guideline (DO NOT EDIT) [5]

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### Diuretics and Decongestion Strategies in Patients with HF (DO NOT EDIT)[5][6][7]

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Class I

"1. In patients with HF who have fluid retention, diuretics are recommended to relieve congestion, improve symptoms, and prevent worsening HF. [8][9][10][11][12] (Level of Evidence: B-NR) "
"2. For patients with HF and congestive symptoms, addition of a thiazide (eg, metolazone) to treatment with a loop diuretic should be reserved for patients who do not respond to moderate or high-dose loop diuretics to minimize electrolyte abnormalities. [13] (Level of Evidence: B-NR) "

##### Mineralocorticoid Receptor Antagonists (MRAs)

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Class I

"1. In patients with HFrEF and NYHA class II to IV symptoms, an MRA (spironolactone or epleronone) is recommended to reduce morbidity and mortality, if eGFR is >30 mL/min/1.73 m2 and serum potassium is <5.0 mEq/L. Careful monitoring of potassium, renal function, and diuretic dosing should be performed at initiation and closely monitored thereafter to minimize risk of hyperkalemia and renal insufficiency. [4][14][15] (Level of Evidence: A) "
Value Statement: High Value

"2. In patients with HFrEF and NYHA II to IV symptoms, MRA therapy provides high economic value.[16][17][18][19] (Level of Evidence: A) "
Class III (Harm)

"3. In patients taking MRA whose serum potassium cannot be maintained at <5.5 mEq/L, MRA should be discontinued to avoid life-threatening hyperkalemia. [20][21] (Level of Evidence: B-NR) "

## External Link

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* 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines[22]

## References

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1. ↑ Mullens W, Damman K, Harjola VP, Mebazaa A, Brunner-La Rocca HP, Martens P, Testani JM, Tang W, Orso F, Rossignol P, Metra M, Filippatos G, Seferovic PM, Ruschitzka F, Coats AJ (February 2019). "The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology". Eur J Heart Fail. 21 (2): 137–155. doi:10.1002/ejhf.1369. PMID 30600580. Vancouver style error: initials (help)
2. ↑ Faris R, Flather M, Purcell H, Henein M, Poole-Wilson P, Coats A (February 2002). "Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomised controlled trials". Int J Cardiol. 82 (2): 149–58. doi:10.1016/s0167-5273(01)00600-3. PMID 11853901.
3. ↑ Rohde LE, Rover MM, Figueiredo Neto JA, Danzmann LC, Bertoldi EG, Simões MV, Silvestre OM, Ribeiro A, Moura LZ, Beck-da-Silva L, Prado D, Sant'Anna RT, Bridi LH, Zimerman A, Raupp da Rosa P, Biolo A (November 2019). "Short-term diuretic withdrawal in stable outpatients with mild heart failure and no fluid retention receiving optimal therapy: a double-blind, multicentre, randomized trial". Eur Heart J. 40 (44): 3605–3612. doi:10.1093/eurheartj/ehz554. PMID 31424503. Vancouver style error: initials (help)
4. ↑ 4.0 4.1 Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (September 1999). "The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators". N Engl J Med. 341 (10): 709–17. doi:10.1056/NEJM199909023411001. PMID 10471456.
5. ↑ 5.0 5.1 Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM; et al. (2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 145 (18): e876–e894. doi:10.1161/CIR.0000000000001062. PMID 35363500 Check `|pmid=` value (help).CS1 maint: Multiple names: authors list (link)
6. ↑ Yancy CW, Jessup M, Bozkurt B, Masoudi FA, Butler J, McBride PE; et al. (2013). "2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. doi:10.1016/j.jacc.2013.05.019. PMID 23747642.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
7. ↑ Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG et al. (2009) 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119 (14):1977-2016. DOI:10.1161/CIRCULATIONAHA.109.192064 PMID:19324967
8. ↑ Patterson JH, Adams KF, Applefeld MM, Corder CN, Masse BR (1994). "Oral torsemide in patients with chronic congestive heart failure: effects on body weight, edema, and electrolyte excretion. Torsemide Investigators Group". Pharmacotherapy. 14 (5): 514–21. PMID 7997385.CS1 maint: Multiple names: authors list (link)
9. ↑ Goebel KM (1993). "Six-week study of torsemide in patients with congestive heart failure". Clin Ther. 15 (6): 1051–9. PMID 8111802.
10. ↑ Wilson JR, Reichek N, Dunkman WB, Goldberg S (1981). "Effect of diuresis on the performance of the failing left ventricle in man". Am J Med. 70 (2): 234–9. doi:10.1016/0002-9343(81)90755-5. PMID 7468610.CS1 maint: Multiple names: authors list (link)
11. ↑ Parker JO (1993). "The effects of oral ibopamine in patients with mild heart failure--a double blind placebo controlled comparison to furosemide. The Ibopamine Study Group". Int J Cardiol. 40 (3): 221–7. doi:10.1016/0167-5273(93)90004-z. PMID 8225657.
12. ↑ Richardson A, Bayliss J, Scriven AJ, Parameshwar J, Poole-Wilson PA, Sutton GC (1987). "Double-blind comparison of captopril alone against frusemide plus amiloride in mild heart failure". Lancet. 2 (8561): 709–11. doi:10.1016/s0140-6736(87)91074-9. PMID 2888942.CS1 maint: Multiple names: authors list (link)
13. ↑ Grodin JL, Stevens SR, de Las Fuentes L, Kiernan M, Birati EY, Gupta D; et al. (2016). "Intensification of Medication Therapy for Cardiorenal Syndrome in Acute Decompensated Heart Failure". J Card Fail. 22 (1): 26–32. doi:10.1016/j.cardfail.2015.07.007. PMC 4706474. PMID 26209004.CS1 maint: Multiple names: authors list (link)
14. ↑ Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B; et al. (2003). "Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction". N Engl J Med. 348 (14): 1309–21. doi:10.1056/NEJMoa030207. PMID 12668699.CS1 maint: Multiple names: authors list (link)  Review in: J Fam Pract. 2003 Aug;52(8):598-9 Review in: ACP J Club. 2003 Sep-Oct;139(2):32
15. ↑ Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H; et al. (2011). "Eplerenone in patients with systolic heart failure and mild symptoms". N Engl J Med. 364 (1): 11–21. doi:10.1056/NEJMoa1009492. PMID 21073363.CS1 maint: Multiple names: authors list (link)  Review in: Evid Based Med. 2011 Aug;16(4):121-2 Review in: J Fam Pract. 2011 Aug;60(8):482-4
16. ↑ Banka G, Heidenreich PA, Fonarow GC (2013). "Incremental cost-effectiveness of guideline-directed medical therapies for heart failure". J Am Coll Cardiol. 61 (13): 1440–6. doi:10.1016/j.jacc.2012.12.022. PMID 23433562.CS1 maint: Multiple names: authors list (link)
17. ↑ Glick HA, Orzol SM, Tooley JF, Remme WJ, Sasayama S, Pitt B (2002). "Economic evaluation of the randomized aldactone evaluation study (RALES): treatment of patients with severe heart failure". Cardiovasc Drugs Ther. 16 (1): 53–9. doi:10.1023/a:1015371616135. PMID 12085979.CS1 maint: Multiple names: authors list (link)
18. ↑ Weintraub WS, Zhang Z, Mahoney EM, Kolm P, Spertus JA, Caro J; et al. (2005). "Cost-effectiveness of eplerenone compared with placebo in patients with myocardial infarction complicated by left ventricular dysfunction and heart failure". Circulation. 111 (9): 1106–13. doi:10.1161/01.CIR.0000157146.86758.BC. PMID 15723981.CS1 maint: Multiple names: authors list (link)
19. ↑ Zhang Z, Mahoney EM, Kolm P, Spertus J, Caro J, Willke R; et al. (2010). "Cost effectiveness of eplerenone in patients with heart failure after acute myocardial infarction who were taking both ACE inhibitors and beta-blockers: subanalysis of the EPHESUS". Am J Cardiovasc Drugs. 10 (1): 55–63. doi:10.2165/11319940-000000000-00000. PMID 20104935.CS1 maint: Multiple names: authors list (link)
20. ↑ Hernandez AF, Mi X, Hammill BG, Hammill SC, Heidenreich PA, Masoudi FA; et al. (2012). "Associations between aldosterone antagonist therapy and risks of mortality and readmission among patients with heart failure and reduced ejection fraction". JAMA. 308 (20): 2097–107. doi:10.1001/jama.2012.14795. PMID 23188026.CS1 maint: Multiple names: authors list (link)
21. ↑ Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A; et al. (2004). "Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study". N Engl J Med. 351 (6): 543–51. doi:10.1056/NEJMoa040135. PMID 15295047.CS1 maint: Multiple names: authors list (link)
22. ↑ Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW (May 2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 145 (18): e895–e1032. doi:10.1161/CIR.0000000000001063. PMID 35363499 Check `|pmid=` value (help).

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