What is the role of furosemide, spironolactone, propranolol, and Angiotensin-Converting Enzyme Inhibitors (ACE-I) in the management of heart failure?

Management of Heart Failure with Furosemide, Spironolactone, Propranolol, and ACE Inhibitors

ACE inhibitors and beta-blockers (not propranolol specifically) are first-line therapy for all patients with heart failure and reduced ejection fraction, followed by spironolactone for persistent NYHA class III-IV symptoms, with furosemide reserved for managing fluid overload. 1, 2

First-Line Therapy: ACE Inhibitors + Beta-Blockers

Both medications should be initiated simultaneously as first-line treatment in all NYHA class I-IV heart failure patients unless contraindicated. 1, 2

ACE Inhibitor Role and Implementation

ACE inhibitors provide the strongest mortality and morbidity benefits in heart failure:

• Prevent 13 deaths per 1000 patient-years and reduce hospitalizations by 99 per 1000 patient-years 1
• Improve survival, symptoms, functional capacity, and quality of life across all grades of symptomatic heart failure 1, 3
• Delay or prevent development of symptomatic heart failure in asymptomatic left ventricular dysfunction 1, 3

Start low and titrate to target doses proven in clinical trials, not based on symptom improvement alone: 1, 4

ACE Inhibitor	Starting Dose	Target Dose
Enalapril	2.5 mg twice daily	10-20 mg twice daily
Lisinopril	2.5-5.0 mg once daily	30-35 mg once daily
Ramipril	2.5 mg once daily	5 mg twice daily or 10 mg once daily

• Double the dose at minimum 2-week intervals 1
• Monitor blood chemistry (urea, creatinine, potassium) and blood pressure before initiation, 1-2 weeks after each dose increment 1, 3

Critical monitoring thresholds: 1, 2

• Accept creatinine increases up to 50% above baseline or to 3 mg/dL (266 µmol/L), whichever is greater
• Accept potassium up to 5.5 mmol/L
• Asymptomatic hypotension does not require dose adjustment 1

Seek specialist advice before initiating if: 1, 2

• Creatinine >2.5 mg/dL (>221 µmol/L)
• Potassium >5.0 mmol/L
• Symptomatic hypotension or systolic BP <90 mmHg

Beta-Blocker Role (Not Propranolol)

The evidence base for beta-blockers in heart failure is established only for bisoprolol, metoprolol succinate, carvedilol, and nebivolol—propranolol is not recommended. 1

Beta-blockers provide substantial mortality benefit:

• Prevent 38 deaths per 1000 patient-years 1
• Reduce morbidity and increase survival in left ventricular systolic dysfunction 1
• Should be initiated in stable patients only, not during acute decompensation 2

Initiate with "start-low, go-slow" approach: 1

• Review heart rate, blood pressure, and clinical status after each dose titration
• Avoid in NYHA class IV with severe decompensation, current hospitalization for worsening heart failure, or heart rate <60 bpm 2

Second-Line Therapy: Spironolactone

Add spironolactone to ACE inhibitor + beta-blocker therapy in patients with persistent moderate to severe symptoms (NYHA class III-IV). 1, 2

Spironolactone provides the highest mortality benefit among heart failure medications:

• Prevents 57 deaths per 1000 patient-years—more than ACE inhibitors or beta-blockers 1, 2
• Increases survival, reduces hospitalizations by 138 per 1000 patient-years, and improves NYHA class 1

Dosing protocol: 1

• Start at 25 mg once daily or on alternate days
• Target dose: 25-50 mg once daily
• Check blood chemistry at 1,4,8, and 12 weeks; then at 6,9, and 12 months; then every 6 months 1

Critical safety monitoring: 1, 2

• If potassium rises to 5.5-6.0 mmol/L or creatinine to 2.5 mg/dL (221 µmol/L), reduce dose to 25 mg on alternate days
• If potassium >6.0 mmol/L, seek specialist advice immediately
• Avoid concomitant potassium supplements, potassium-sparing diuretics, NSAIDs, and "low salt" substitutes with high potassium content 1

Furosemide: Symptom Management Only

Furosemide is reserved for managing fluid overload (peripheral edema, elevated JVP, pulmonary congestion) and does not improve mortality. 2, 5

Loop diuretics role:

• Relieve congestive symptoms by inducing sodium and water excretion 5
• Have not been shown to prolong life in heart failure patients 5
• Should be optimized to achieve euvolemia before or during ACE inhibitor/beta-blocker titration 2

When combining with spironolactone for fluid management: 6

• Optimal dose combination is furosemide 20 mg/day + spironolactone 40 mg/day for NYHA class I-II patients
• This combination significantly improves clinical symptoms, left ventricular function, and reduces re-hospitalization rates compared to higher doses 6
• Higher doses (furosemide 40 mg + spironolactone 100 mg) increase electrolyte disorders without additional benefit 6

Common Pitfalls to Avoid

Do not use diuretics alone for long-term therapy: 7

• Plasma renin activity, angiotensin II, aldosterone, norepinephrine, and vasopressin levels may increase with diuretics alone

Do not stop at symptom relief with ACE inhibitors: 3, 4

• Titrate to target doses proven in clinical trials, not based on symptomatic improvement alone
• Some ACE inhibitor is better than no ACE inhibitor if target dose cannot be reached 1

Do not discontinue ACE inhibitors for asymptomatic hypotension: 1

• Asymptomatic low blood pressure does not require dose reduction

Do not use propranolol: 1

• Only bisoprolol, metoprolol succinate, carvedilol, and nebivolol have proven efficacy in heart failure

Do not add spironolactone without careful potassium monitoring: 1

• Major concern is hyperkalemia >6.0 mmol/L, which requires immediate specialist consultation