What are the treatments for heart failure resistant to Lasix (furosemide)?

From the Guidelines

Treatment for Lasix-Resistant Heart Failure

For patients with Lasix-resistant heart failure, treatment may involve the addition of a thiazide diuretic, such as metolazone, at a dose of 2.5-5mg orally once daily, or a mineralocorticoid receptor antagonist, such as spironolactone, at a dose of 25-50mg orally once daily 1.

• Key considerations include:
  • Restricting sodium and water intake
  • Increasing the dose and/or frequency of diuretic administration
  • Using intravenous administration of diuretics, such as furosemide, which may be more effective than oral administration 1
  • Combining diuretic therapy, such as furosemide + metolazone, which can be effective even in renal failure 1
• In severe cases, the use of inotropic agents, such as dobutamine, may be necessary, typically administered intravenously at a dose of 2-5 µg/kg/min, with continuous hemodynamic monitoring 1.
• It is also important to monitor electrolyte levels and adjust treatment accordingly, as severe electrolyte and volume depletion can occur with combination diuretic therapy 1.
• Additionally, potassium chloride may be required to maintain serum potassium levels in the 4.5- to 5.0-mEq/liter range, and digitalis glycosides, such as digoxin, may be used to increase left ventricular ejection fraction and exercise tolerance in patients with symptomatic left ventricular systolic dysfunction and sinus rhythm 1.

From the FDA Drug Label

Successful treatment with bumetanide following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity. There is limited experience with the combination of metolazone tablets, USP, and furosemide in pediatric patients with furosemide-resistant edema. Some benefited while others did not or had an exaggerated response with hypovolemia, tachycardia, and orthostatic hypotension requiring fluid replacement

The treatments for heart failure resistant to Lasix (furosemide) are:

• Bumetanide: may be used as an alternative due to a lack of cross-sensitivity with furosemide 2
• Metolazone: may be used in combination with furosemide for furosemide-resistant edema, but close clinical and laboratory monitoring is indicated due to potential for adverse reactions 3
• Torsemide: may be used as an alternative, but there is no direct information in the label regarding its use in furosemide-resistant heart failure 4

From the Research

Treatments for Heart Failure Resistant to Lasix (Furosemide)

• The following treatments have been studied for heart failure resistant to Lasix (furosemide):
  • Adding thiazide-type diuretics, such as metolazone, to loop diuretics like furosemide 5, 6, 7, 8
  • Using metolazone as an adjuvant therapy to furosemide, which was found to be not associated with higher morbidity and mortality 5
  • Comparing metolazone to chlorothiazide as add-on therapy to loop diuretics, with metolazone being as effective as chlorothiazide in augmenting loop diuretic therapy in ADHF 6, 7
  • Sequential nephron blockade with either metolazone or chlorothiazide, which appears to be efficacious and safe in ADHF, renal dysfunction, and diuretic resistance 7
  • Increasing the dose size, administering frequent 'small' doses, continuous intravenous infusion of the diuretic, or concomitant administration of another diuretic such as metolazone or hydrochlorothiazide to overcome resistance to loop diuretics 8
  • Using dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, compared to metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide, with dapagliflozin not being more effective at relieving congestion than metolazone 9

Comparison of Treatments

• Metolazone and chlorothiazide have been compared as add-on therapy to loop diuretics, with metolazone being as effective as chlorothiazide in most studies 6, 7
• Dapagliflozin has been compared to metolazone in patients with heart failure and loop diuretic resistance, with dapagliflozin not being more effective at relieving congestion than metolazone 9

Safety and Efficacy

• The safety and efficacy of metolazone and chlorothiazide as add-on therapy to loop diuretics have been evaluated, with both being found to be safe and effective in most studies 6, 7
• The safety and efficacy of dapagliflozin compared to metolazone have been evaluated, with dapagliflozin being found to have less biochemical upset than metolazone 9