Loop diuretic use in heart failure

ROLE OF LOOP DIURETICS IN TREATMENT OF HEART FAILURE ㅡ Loop diuretics are recommended for all volume overloaded patients with NYHA class II to IV heart failure to improve symptoms, exercise tolerance, and efficacy of other heart failure medications (e.g., beta-blockers).

Thiazide could be used instead of a loop for patients with mild fluid retention and hypertension, for blood pressure control. Unlike potassium-sparing diuretics (e.g., spironolactone, eplerenone), loop diuretics have not been shown to reduce the risk of death. Ethacrynic acid is rarely used because data on ethacrynic acid in heart failure is lacking. It may be more ototoxic than other loops and the most expensive loop diuretic. Ethacrynic acid does not contain a sulfa group and is a possible alternative in sulfonamide-allergic patients.

How do loop diuretics compare

Bioavailability, bumetanide and torsemide have better bioavailability (i.e. less erratic absorption) than furosemide, so some patients will respond better to them than to furosemide. Furosemide bioavailability is about 50% (range 10% to 90%) AND torsemide and bumetanide bioavailability is > 80% to 90%. Cost, furosemide (Lasix) is the least expensive loop diuretic. Efficacy, torsemide (Examide) benefits over furosemide in regard to heart failure hospitalization and improvement in NYHA functional class have not been proven at equivalent doses. There is not much data with bumetanide in heart failure.

Dosage

GENERAL CONCEPTS ㅡ High sodium intake and NSAID use reduces diuretic efficacy. In heart failure with preserved ejection fraction, diuretics must be dosed cautiously because preload reduction can cause reduced cardiac output with hypotension and renal impairment. Start with a low dose, and increase to achieve target weight (e.g., a 0.5 to 1 kg weight loss daily to goal) and symptoms then titrate to eliminate clinical signs/symptoms of fluid overload without causing hypotension or renal insufficiency, or limiting the up-titration of disease-modifying agents (e.g., ACEIs, ARBs, potassium-sparing diuretics).

Not all patients will need a daily scheduled dose. Consider transitioning to as-needed use once patients are stable and receiving optimized guideline-directed medical therapy (i.e., beta-blockers and inhibitors of the renin-angiotensin system), without signs of fluid retention. Patients can self-titrate dose based on daily weights. Giving furosemide (Lasix) or bumetanide (Burinex) twice daily might improve efficacy. But first, try increasing the once-daily dose to the maximum single dose (or where there’s no further diuresis); diuresis depends on how high the loop concentration gets in the urine. If furosemide or bumetanide is given twice daily, give the second dose in the afternoon to minimize nocturia. Check renal function and electrolytes at baseline and one to two weeks after initiation or dosage increase.

• Dosing of loops for chronic heart failure
• Furosemide, initial 20 to 40 mg once or twice daily; max total daily dose 240 mg (600 mg in renal impairment).
• Bumetanide, initial 0.5 to 1 mg once or twice daily; max total daily dose 10 mg.
• Torsemide, initial 10 to 20 mg once daily; max total daily dose 200 mg.

Considerations when switching loop diuretics

General Considerations ㅡ Furosemide is the most commonly used loop diuretic. A switch to bumetanide or torsemide could be considered for patients: (1) Who require hospitalization for acute heart failure despite furosemide use. (2) Who are not achieving good symptomatic control despite optimization of guideline-directed medical therapy and furosemide. (3) Who may have impaired furosemide absorption due to splanchnic congestion. Consider switching to torsemide rather than bumetanide; torsemide has a longer duration of action and more evidence in heart failure.

• Dosing considerations
• Bumetanide 0.5 to 1 mg orally = furosemide 40 mg orally.
• Torsemide 10 to 20 mg orally = furosemide 40 mg orally, Oral furosemide bioavailability is only about 50%.
• Ethacrynic acid 50 mg orally ~ furosemide 40 mg orally.

Diuretics combination

Can other diuretics be combined with loops to improve response? Switching from furosemide to bumetanide or torsemide may be preferable to adding a thiazide to improve response, as combining diuretics increases the risk of electrolyte disturbances. Consider adding spironolactone or eplerenone before trying a thiazide; spironolactone and eplerenone provide some diuresis, offset potassium loss, and improve outcomes, particularly in heart failure with reduced ejection fraction. If a thiazide is added, it is not necessary to time the thiazide so that it is given prior to the loop. For example, there is no proof that giving the thiazide 30 minutes before the loop provides better diuresis. Contrary to popular belief, thiazides can be effective if CrCl is < 30 mL/min. Metolazone may be most effective.

References

• Rohde, L.E., Rover, M.M., and Others (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. European Heart Journal, [online] 40(44), pp.3605–3612. Available at: https://pubmed.ncbi.nlm.nih.gov/31424503

  Kido, K., Shimizu, M. and Hashiguchi, M. (2019). Comparing torsemide versus furosemide in patients with heart failure: A meta-analysis. Journal of the American Pharmacists Association, 59(3), pp.432–438. Available at: https://pubmed.ncbi.nlm.nih.gov/30846351

  Diuretic use, progressive heart failure, and death in patients in the studies of left ventricular dysfunction (SOLVD). (2003). Journal of the American College of Cardiology, [online] 42(4), pp.705–708. Available at: https://www.sciencedirect.com/science/article/pii/S0735109703007654

  Yancy, C.W., Jessup, M., and Others (2013). 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation, 128(16). Available at: https://pubmed.ncbi.nlm.nih.gov/23741058

  Mullens, W., Damman, K., Harjola, V.-P., and Others (2019). The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology. European Journal of Heart Failure, 21(2), pp.137–155. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.1369