Can sacubitril-valsartan (Entresto) and/or dapagliflozin (Farxiga) and/or metolazone help when given with furosemide (Lasix) and spironolactone for a patient with volume overload and congestive heart failure (CHF) to improve volume status in the setting of impaired renal function?

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Last updated: May 18, 2025View editorial policy

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From the Guidelines

For a patient with volume overload and heart failure with reduced ejection fraction (HFrEF) who has a GFR of 22 and creatinine of 172, adding dapagliflozin to the current regimen of Lasix and spironolactone is the most appropriate option to improve volume status. Dapagliflozin has shown benefit in heart failure patients with eGFR as low as 20, and its glucose-independent mechanism to promote osmotic diuresis can help reduce heart failure hospitalizations even in patients with reduced kidney function 1. The initial dose of dapagliflozin should be 10mg daily, with close monitoring of kidney function, as recommended by recent guidelines 1. Metolazone could be considered as a short-term option (2.5-5mg) to enhance diuresis when combined with Lasix, particularly for diuretic resistance, but its use should be cautious due to risks of electrolyte abnormalities and further kidney function decline 1. Sacubitril-valsartan should be used with extreme caution at this level of kidney dysfunction, and if considered, start at the lowest dose (24/26mg twice daily) with close monitoring of potassium, blood pressure, and kidney function 1. Key considerations for these additions include:

  • Careful monitoring of electrolytes, kidney function, and volume status
  • Temporary discontinuation if kidney function worsens significantly or electrolyte abnormalities develop
  • Adjusting diuretic dosages based on patient response and kidney function, as diuretic resistance can be overcome by combining loop diuretics and thiazides or using diuretics together with drugs that increase renal blood flow 1.

From the Research

Volume Overload Treatment in CHFe

  • The use of sacubitril-valsartan, dapagliflozin, and metolazone in conjunction with Lasix and spironolactone for treating volume overload in patients with congestive heart failure (CHF) is a complex issue, with various studies providing insights into their potential benefits and limitations 2, 3, 4, 5.
  • Sacubitril-valsartan has been shown to reduce mortality and hospitalization rates in patients with heart failure with reduced ejection fraction (HFrEF) 3.
  • Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, has been found to improve outcomes in patients with heart failure, including those with reduced ejection fraction, by reducing volume overload and improving cardiac function 4.
  • Metolazone, a thiazide-like diuretic, can be used in combination with loop diuretics like Lasix to enhance diuresis and improve volume status in patients with CHF 4, 5.
  • However, the effectiveness of these medications in patients with poor renal function, such as a GFR of 22 and creatinine of 172, may be limited due to the increased risk of worsening renal function and electrolyte imbalances 2, 4, 5.

Renal Function Considerations

  • The close interrelationship between the heart and kidneys means that volume overload can exacerbate renal dysfunction, and vice versa 2, 4.
  • The use of diuretics, including Lasix and metolazone, can stimulate the renin-angiotensin-aldosterone system (RAAS) and lead to adaptive responses like diuretic resistance, neurohormonal activation, and worsening renal function 5.
  • Sacubitril-valsartan, which inhibits neprilysin and blocks the angiotensin II receptor, may have beneficial effects on renal function, particularly in patients with type 2 diabetes mellitus 3.

Treatment Strategies

  • Ultrafiltration (UF) is an emerging therapy for treating volume overload in ADHF patients, which can improve volume regulation while preserving renal and cardiac function 2, 5.
  • Non-pharmacological strategies, such as sodium restriction, fluid restriction, telemonitoring, and invasive hemodynamic monitoring, can also be effective in managing volume overload in patients with CHF 4, 5.
  • A comprehensive treatment approach that incorporates both pharmacological and non-pharmacological strategies may be necessary to optimize volume status and improve outcomes in patients with CHFe 4, 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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