What is the role of diuretics (e.g. furosemide, torsemide) and oral inotropes (e.g. digoxin) in managing heart failure?

Role of Diuretics and Oral Inotropes in Heart Failure Management

Diuretics: Essential for Symptom Control

Diuretics are recommended for all heart failure patients with current or prior evidence of fluid retention to relieve congestion and improve symptoms, but they must always be combined with guideline-directed medical therapy (ACE inhibitors/ARBs, beta-blockers, and aldosterone antagonists) as they do not reduce mortality when used alone. 1

Loop Diuretics as First-Line Therapy

• Loop diuretics (furosemide, torsemide, bumetanide) are the preferred diuretic class for most heart failure patients because they maintain efficacy even with impaired renal function and can increase sodium excretion up to 20-25% of filtered load 2

• Start with furosemide 20-40 mg once or twice daily (or torsemide 10-20 mg once daily, or bumetanide 0.5-1.0 mg once or twice daily) and titrate upward until urine output increases and weight decreases by 0.5-1.0 kg daily 1, 2

• Maximum doses are furosemide 600 mg/day, torsemide 200 mg/day, and bumetanide 10 mg/day 1

Choosing Between Loop Diuretics

• Furosemide remains the most commonly used loop diuretic, though torsemide and bumetanide may offer advantages due to increased oral bioavailability 1

• The TRANSFORM-HF trial (2023) found no mortality difference between torsemide and furosemide (26.1% vs 26.2% mortality; HR 1.02,95% CI 0.89-1.18) in 2,859 patients followed for median 17.4 months 3

• However, meta-analysis data suggest torsemide may reduce heart failure hospitalizations (RR 0.60,95% CI 0.43-0.83) and cardiovascular hospitalizations (RR 0.72,95% CI 0.60-0.88) compared to furosemide 4

• Given equivalent mortality but potential hospitalization benefits, either furosemide or torsemide is acceptable, with torsemide preferred if compliance is a concern due to its longer duration of action (12-16 hours vs 6-8 hours for furosemide) 1

Maintenance and Monitoring Strategy

• Instruct patients to record daily weights and adjust diuretic dose if weight increases or decreases beyond a specified range (typically ±2 kg from target dry weight) 1, 2

• The goal is to eliminate all clinical evidence of fluid retention using the lowest dose possible to maintain euvolemia 1

• Monitor for electrolyte depletion (potassium, magnesium), hypotension, and azotemia, which are the principal adverse effects 1

Managing Diuretic Resistance

• If adequate diuresis is not achieved with moderate-to-high dose loop diuretics alone, add a thiazide diuretic (metolazone 2.5-10 mg once daily or hydrochlorothiazide 25-100 mg once or twice daily) for sequential nephron blockade 1

• Reserve thiazide combination therapy for patients who do not respond to moderate or high-dose loop diuretics to minimize electrolyte abnormalities, particularly hypokalemia 1

• The risk of electrolyte depletion is markedly enhanced when two diuretics are combined, requiring close monitoring 1

• Alternative strategies include switching to intravenous administration, increasing dosing frequency to twice daily, or adding vasodilators to reduce diuretic requirements 1

Critical Dosing Pitfalls to Avoid

• Inappropriately low diuretic doses result in persistent fluid retention, which diminishes response to ACE inhibitors and increases risk with beta-blocker initiation 1, 2

• Inappropriately high diuretic doses cause volume contraction, increasing risk of hypotension (especially when initiating ACE inhibitors or vasodilators) and renal insufficiency 1, 2

• In patients with systolic blood pressure <90 mmHg, hold diuretics until adequate perfusion is restored as they worsen hypotension and end-organ perfusion 2

Essential Concurrent Therapy

• Diuretics must never be used as monotherapy in chronic heart failure but always combined with ACE inhibitors (or ARBs), beta-blockers, and aldosterone antagonists to reduce hospitalizations and mortality 1, 5

• Concomitant use of ACE inhibitors or aldosterone antagonists prevents electrolyte depletion in most patients, often eliminating the need for long-term potassium supplementation 1

Oral Inotropes: Limited Role with Digoxin

Digoxin is indicated for heart failure patients to improve symptoms, exercise capacity, and reduce heart failure hospitalizations, but it has no effect on mortality and should be used with a diuretic and ACE inhibitor. 6

Specific Indications for Digoxin

• Digoxin is most appropriate for patients with heart failure and reduced ejection fraction who remain symptomatic despite optimal guideline-directed medical therapy (ACE inhibitors/ARBs, beta-blockers, aldosterone antagonists, and diuretics) 6

• Digoxin is also indicated for rate control in heart failure patients with chronic atrial fibrillation 6

Key Limitations

• Digoxin improves left ventricular ejection fraction and symptoms but does not reduce mortality, making it an adjunctive rather than foundational therapy 6

• The optimal order for starting digoxin, diuretics, and ACE inhibitors cannot be specified, but all three should be used together when indicated 6

• Monitor for digoxin toxicity, particularly in patients with hypokalemia or hypomagnesemia from diuretic therapy, as electrolyte depletion predisposes to serious cardiac arrhythmias 1