What is the gold standard for treatment of heart failure?

Gold Standard Treatment for Heart Failure

The gold standard for heart failure treatment depends on ejection fraction: for HF with reduced ejection fraction (HFrEF), initiate quadruple therapy with ACE inhibitors (or ARNI), beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, while for HF with preserved ejection fraction (HFpEF), use SGLT2 inhibitors and diuretics as primary therapy.

Heart Failure with Reduced Ejection Fraction (HFrEF)

Foundational Quadruple Therapy

All patients with HFrEF should receive four medication classes simultaneously, as these reduce both mortality and morbidity:

• ACE inhibitors are first-line therapy that reduce morbidity and increase survival in patients with left ventricular systolic dysfunction 1
• Beta-blockers reduce mortality in all age groups and should be initiated in all patients with NYHA class II-IV heart failure on standard treatment 1, 2
• Mineralocorticoid receptor antagonists (MRAs) such as spironolactone improve survival and morbidity in advanced heart failure (NYHA III-IV) and should be started as soon as possible 1, 3
• SGLT2 inhibitors provide mortality benefit with minimal blood pressure effects and should be considered early in treatment 3, 4

Alternative to ACE Inhibitors

• Sacubitril/valsartan (ARNI) is superior to enalapril alone, reducing the combined endpoint of cardiovascular death or heart failure hospitalization (HR 0.80,95% CI 0.73-0.87, p<0.0001) and should be considered instead of an ACE inhibitor in appropriate patients 3, 5
• ARBs are an alternative only when ACE inhibitors are not tolerated, as they reduce hospitalizations and improve quality of life but lack clear mortality benefit compared to ACE inhibitors 1

Initiation Strategy

Start multiple medications simultaneously at low doses rather than sequentially reaching target doses:

• Begin ACE inhibitors at low doses and titrate to target doses achieved in clinical trials, monitoring blood pressure, renal function, and electrolytes 1-2 weeks after each increment 2
• Initiate beta-blockers only when patients are relatively stable without marked fluid retention or need for intravenous inotropes, starting at very low doses and doubling every 1-2 weeks as tolerated 1, 2
• For patients with low blood pressure, start with medications having minimal BP effects (SGLT2 inhibitors and MRAs) before introducing ACE inhibitors/ARBs and beta-blockers 3
• Avoid excessive diuresis before starting ACE inhibitors and temporarily reduce or withhold diuretics for 24 hours if possible 2

Dose Titration

• Gradually increase to target doses over 6-12 weeks with close monitoring of symptoms, blood pressure, and renal function 3
• High-quality evidence shows the same outcomes whether ACE inhibitor or beta-blocker therapy is started first 1
• Renal function and electrolytes should be checked 1-2 weeks after each dose increment, at 3 months, and subsequently at 6-month intervals 3, 2

Additional Therapies for Persistent Symptoms

• Digoxin improves clinical status in patients with persistent symptoms despite ACE inhibitor and diuretic treatment, with usual daily dose of 0.25-0.375 mg if renal function is normal 1
• Ivabradine may be considered if beta-blockers are not well tolerated hemodynamically, especially if heart rate remains elevated above 70 bpm, reducing the risk of hospitalization for worsening heart failure (HR 0.82,95% CI 0.75-0.90) 3, 6
• Hydralazine plus nitrate combination should be used in patients intolerant of both ACE inhibitors and ARBs 1

Device Therapy Considerations

• Specialist referral is warranted for consideration of cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) in patients with persistent symptoms 1

Heart Failure with Preserved Ejection Fraction (HFpEF)

There is insufficient evidence to recommend specific therapies beyond treatment of comorbidities and symptom management:

• SGLT2 inhibitors are first-line therapy providing mortality benefit 3, 4
• Diuretics manage fluid retention and are essential for symptomatic treatment when pulmonary congestion or peripheral edema is present 1, 2
• Treatment of comorbid conditions such as diabetes mellitus, ischemic heart disease, and atrial fibrillation is crucial 1, 4

Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)

Use the same quadruple therapy approach as HFrEF:

• ACE inhibitors (or ARBs if contraindicated) should be started as soon as possible with blood pressure and renal function monitoring 3
• Beta-blockers should be initiated at low doses and gradually titrated after patient stabilization 3
• MRAs and SGLT2 inhibitors should be started early as they have minimal blood pressure effects 3

Critical Pitfalls to Avoid

• Never use NSAIDs as they worsen renal function and counteract beneficial effects of heart failure medications 3, 2
• Avoid potassium-sparing diuretics during initiation of ACE inhibitor therapy due to hyperkalemia risk 2
• Do not use routine inotropic therapy as it increases mortality; reserve for severe decompensation episodes only 2
• Underutilization and inadequate dose titration are the most common management errors—always push toward target doses as tolerated 3
• Beta-blockers are contraindicated in patients with asthma, severe bronchial disease, or symptomatic bradycardia/hypotension 1, 2

Non-Pharmacological Management

• Explain heart failure pathophysiology, symptom recognition, and self-management to patients 2
• Encourage daily physical and leisure activities in stable patients to prevent muscle deconditioning 2
• Control sodium intake when necessary, especially in severe heart failure 2
• Avoid excessive fluids and alcohol intake in severe heart failure 2
• Consider exercise training programs in stable NYHA II-III patients 2