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

From the Guidelines

Heart failure resistant to Lasix (furosemide) can be treated with alternative loop diuretics, such as bumetanide or torsemide, or a combination of different diuretic classes, including thiazide diuretics like metolazone.

Treatment Options

• Alternative loop diuretics:
  • Bumetanide: initial dose 0.5-1.0 mg once or twice, maximum dose 10 mg 1
  • Torsemide: initial dose 10-20 mg once, maximum dose 200 mg 1
• Combination of different diuretic classes:
  • Metolazone: initial dose 2.5 mg once, maximum dose 20 mg, can be used in combination with a loop diuretic 1
  • Other thiazide diuretics, such as chlorthalidone or hydrochlorothiazide, can also be used in combination with a loop diuretic 1

Rationale

Diuretic resistance can be overcome by escalating the dose of the loop diuretic, using intravenous administration, or combining different diuretic classes 1. The choice of treatment depends on the individual patient's response and the severity of their heart failure. Patients who are resistant to furosemide may respond better to other loop diuretics, such as bumetanide or torsemide, due to their increased oral bioavailability 1. Combination therapy with a thiazide diuretic, such as metolazone, can also be effective in overcoming diuretic resistance 1.

Important Considerations

• Patients should be monitored closely for signs of dehydration, hypotension, and renal dysfunction when using diuretics, especially when combining different classes 1.
• Dietary sodium restriction is also important in managing heart failure and can help reduce the need for high doses of diuretics 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, which showed that metolazone is as effective as chlorothiazide in treating acute decompensated heart failure (ADHF) without an increase in safety concerns 6, 7
  • Sequential nephron blockade with thiazide-like diuretics, such as 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, which showed that dapagliflozin was not more effective at relieving congestion than metolazone in patients with heart failure and loop diuretic resistance 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 treating ADHF 6, 7
• Dapagliflozin has been compared to metolazone, with dapagliflozin not being more effective at relieving congestion than metolazone in patients with heart failure and loop diuretic resistance 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 treating ADHF 6, 7
• The safety and efficacy of dapagliflozin compared to metolazone have been evaluated, with dapagliflozin being found to cause less biochemical upset than metolazone 9