What is the guideline-directed medical therapy for chronic heart failure?

Guideline-Directed Medical Therapy for Chronic Heart Failure

All patients with chronic heart failure and reduced ejection fraction should receive a foundational combination of four medication classes: ACE inhibitors (or sacubitril/valsartan), beta-blockers, mineralocorticoid receptor antagonists, and diuretics for symptom control, initiated sequentially with careful uptitration to target doses proven in clinical trials. 1

Initial Pharmacological Approach

First-Line Therapy: ACE Inhibitors

• ACE inhibitors are the cornerstone first-line therapy for all patients with reduced left ventricular systolic function, regardless of symptom severity, and must be started immediately unless contraindicated. 1
• Start with low doses: enalapril 2.5 mg twice daily, lisinopril 2.5-5 mg daily, or ramipril 1.25-2.5 mg daily. 1
• Uptitrate every 1-2 weeks to target doses proven effective in trials (e.g., enalapril 10 mg twice daily, lisinopril 20-40 mg daily), not based on symptomatic improvement alone. 1
• If ACE inhibitor causes intolerable cough or angioedema, switch to an angiotensin receptor blocker (valsartan or candesartan). 1

Beta-Blocker Therapy

• Beta-blockers (bisoprolol, carvedilol, or metoprolol succinate) are recommended for all patients with NYHA class II-IV heart failure once euvolemic and stable on ACE inhibitor therapy. 2, 1
• Initiate only after the patient is relatively stable with no intravenous inotropes or marked fluid retention. 1
• Use a "start-low, go-slow" approach: begin with very low doses and uptitrate every 1-2 weeks if the preceding dose is well tolerated. 1
• Target doses: bisoprolol 10 mg daily, carvedilol 50 mg daily, metoprolol succinate 200 mg daily. 1

Mineralocorticoid Receptor Antagonists

• Spironolactone is recommended for advanced heart failure (NYHA class III-IV) in addition to ACE inhibition and diuretics to improve survival and morbidity. 2, 1
• Add spironolactone approximately 25 mg daily when heart failure remains severe despite ACE inhibitor/diuretic therapy and serum potassium is <5.0 mmol/L with acceptable renal function. 1
• Measure serum potassium and creatinine 4-6 days after starting; if potassium rises to ≥5.5 mmol/L, reduce dose by 50% or discontinue. 1

Diuretic Management for Symptom Control

• Diuretics are essential for symptomatic treatment of fluid overload (pulmonary congestion or peripheral edema), providing rapid relief of dyspnea and improved exercise tolerance. 2, 1
• Loop diuretics or thiazides should always be administered together with ACE inhibitors, never as monotherapy. 2, 1
• If glomerular filtration rate is <30 mL/min, avoid thiazides unless combined synergistically with loop diuretics. 1
• For inadequate response: increase loop diuretic dose or give twice daily; combine loop diuretics and thiazides for persistent fluid retention. 1
• In severe chronic heart failure, add metolazone with frequent monitoring of renal function and electrolytes. 1

Advanced Therapy: Sacubitril/Valsartan

• Sacubitril/valsartan should replace ACE inhibitors in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist. 3, 4
• In the PARADIGM-HF trial, sacubitril/valsartan reduced cardiovascular death or heart failure hospitalization compared to enalapril in patients with NYHA class II-IV heart failure and ejection fraction ≤40%. 4
• Allow a 36-hour washout period after stopping ACE inhibitor before initiating sacubitril/valsartan to avoid angioedema risk. 4

Critical Monitoring Protocols

ACE Inhibitor Monitoring

• Reduce or withhold diuretics for 24 hours before initiating ACE inhibitor to avoid excessive diuresis and hypotension. 2, 1
• Check blood pressure, renal function (creatinine, GFR), and electrolytes (potassium, sodium) 1-2 weeks after each dose increase, at 3 months, and then every 6 months. 2, 1
• Discontinue if renal function deteriorates substantially. 2, 1
• Avoid potassium-sparing diuretics during ACE inhibitor initiation to prevent hyperkalemia. 2, 1

Beta-Blocker Monitoring

• Monitor for worsening heart failure symptoms, fluid retention, hypotension, and symptomatic bradycardia during titration. 1
• If symptoms worsen, first optimize diuretic or ACE inhibitor therapy; reduce beta-blocker dose only if necessary. 1
• If hypotension occurs, first reduce vasodilator dose; beta-blocker reduction is a secondary step. 1
• Re-introduce and uptitrate beta-blocker when the patient stabilizes. 1

Additional Pharmacological Considerations

Digoxin

• Digoxin is indicated for atrial fibrillation with any degree of symptomatic heart failure to control ventricular rate and improve symptoms. 1
• In patients in sinus rhythm with persistent heart failure symptoms despite ACE inhibitor and diuretic therapy, digoxin may improve clinical status. 1
• Typical oral dosing: 0.125-0.25 mg daily (lower dose of 0.0625-0.125 mg in older adults with normal renal function). 1

Critical Medications to Avoid

• Non-steroidal anti-inflammatory drugs (NSAIDs) must be avoided because they worsen renal function and promote fluid retention, especially in patients receiving ACE inhibitors. 2, 1
• Avoid diltiazem or verapamil in patients with HFrEF as they increase the risk of heart failure worsening. 3
• Avoid the combination of ACE inhibitor, ARB, and mineralocorticoid receptor antagonist due to increased risk of renal dysfunction and hyperkalemia. 3

Common Clinical Pitfalls

• Inadequate uptitration to target doses is a major cause of suboptimal outcomes—continue increasing doses to trial-proven targets, not just until symptoms improve. 1, 5
• Excessive diuresis can precipitate hypotension and reduced cardiac output, particularly in diastolic dysfunction where preload dependence is critical. 6
• Clinical inertia and unfounded fear of using these medications contribute to underutilization despite proven mortality benefits. 5
• Up to half of patients do not receive target doses for unknown reasons, suggesting a role for clinical inertia by healthcare professionals or patients. 7

Non-Pharmacological Management

• Provide specific education about heart failure, symptom recognition, self-weighing, and reporting weight gains >2 kg in 3 days. 3
• Encourage daily physical activity in stable patients to prevent muscle deconditioning; rest is not encouraged in stable conditions. 2, 3
• Control sodium intake when necessary, especially in severe heart failure; avoid excessive fluid intake in severe HF. 2, 3
• Avoid excessive alcohol intake and refrain from smoking. 2