What is the recommended initial pharmacological treatment and lifestyle modifications for a patient with chronic heart failure?

Recommended Initial Treatment for Chronic Heart Failure

All patients with heart failure and reduced ejection fraction (HFrEF, LVEF ≤40%) should receive quadruple therapy initiated simultaneously at low doses: ACE inhibitors (or sacubitril/valsartan), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors, with aggressive titration to target doses proven to reduce mortality. 1

Initial Pharmacological Therapy

First-Line Medications (Start All Four Classes Together)

ACE Inhibitors or ARNI (Sacubitril/Valsartan):

• ACE inhibitors are the cornerstone of therapy and should be initiated in all patients with reduced left ventricular systolic function, even if asymptomatic 2, 1, 3
• Sacubitril/valsartan is superior to ACE inhibitors alone, reducing cardiovascular death by 20% and heart failure hospitalizations by 21%, and should be considered as replacement therapy in appropriate patients 1, 4
• When switching from an ACE inhibitor to sacubitril/valsartan, allow a mandatory 36-hour washout period to avoid angioedema 5
• Starting dose of sacubitril/valsartan: 49/51 mg twice daily, titrate to target of 97/103 mg twice daily after 2-4 weeks 5

Beta-Blockers:

• Beta-blockers (bisoprolol, carvedilol, or metoprolol succinate) reduce all-cause mortality by 30% and cardiovascular death by 35% 1, 6
• Start with very low doses and double every 1-2 weeks if tolerated, targeting maintenance doses from large trials 2, 6
• Bisoprolol: start 1.25 mg daily, target 10 mg daily 2
• Carvedilol: start 3.125 mg twice daily, target 25-50 mg twice daily 2
• Metoprolol succinate: start 12.5-25 mg daily, target 200 mg daily 2
• Patient must be relatively stable without intravenous inotropic support or marked fluid retention before initiating beta-blockers 6

Mineralocorticoid Receptor Antagonists (MRAs):

• Add spironolactone in patients with NYHA Class III-IV heart failure despite ACE inhibitor and diuretic therapy 1, 3
• Starting dose: 25 mg daily if serum potassium <5.0 mmol/L and creatinine <250 μmol/L 6
• Check potassium and creatinine after 4-6 days of initiation 6

SGLT2 Inhibitors:

• Provide mortality benefit with minimal blood pressure effects and should be initiated early regardless of diabetes status 1, 6
• Represent the fourth pillar of therapy for HFrEF 6

Diuretics (Essential for Symptomatic Relief)

Loop Diuretics or Thiazides:

• Essential for symptomatic treatment when fluid overload manifests as pulmonary congestion or peripheral edema 2, 1
• Result in rapid improvement of dyspnea and increased exercise tolerance 2
• Must always be administered in combination with ACE inhibitors 2, 3
• If GFR <30 mL/min, do not use thiazides except synergistically with loop diuretics 2
• For insufficient response: increase diuretic dose, combine loop diuretics with thiazides, or administer loop diuretics twice daily 2

Critical Dosing Principles

Target doses are non-negotiable—physicians must titrate aggressively to target doses rather than accepting "medium-range" doses 1

ACE Inhibitor Initiation Protocol:

1. Review and potentially reduce diuretics for 24 hours before starting to avoid excessive diuresis 2
2. Start with low dose, preferably in the evening when supine to minimize hypotension 2
3. Build up to recommended maintenance dosages shown effective in large trials 2
4. Check blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, then every 6 months 2

Beta-Blocker Titration Management:

• If worsening symptoms occur during titration, first increase diuretics or ACE inhibitors before reducing beta-blocker dose 2, 6
• For hypotension during titration, reduce vasodilators first rather than the beta-blocker 2, 6
• For bradycardia, reduce or discontinue other heart rate-lowering drugs before adjusting beta-blocker 2

Lifestyle Modifications

Patient Education:

• Explain what heart failure is, why symptoms occur, and how to recognize worsening symptoms 2
• Daily self-weighing to detect early fluid retention 2, 1
• Importance of medication adherence 2

Dietary Modifications:

• Control sodium intake, particularly in severe heart failure 2, 1
• Avoid excessive fluid intake in severe HF 2, 1
• Avoid excessive alcohol intake 2

Physical Activity:

• Rest is not encouraged in stable conditions 2
• Daily physical and leisure activities in stable patients to prevent muscle deconditioning 2
• Exercise training programs in stable NYHA II-III patients 2

Smoking Cessation:

• Refrain from smoking; consider nicotine replacement therapies 2

Common Pitfalls and Critical Warnings

Medication Errors to Avoid:

• Never use potassium-sparing diuretics during ACE inhibitor initiation 2, 3
• Avoid NSAIDs in patients on ACE inhibitors as they worsen renal function 2, 3
• Do not combine ACE inhibitors, ARBs, and MRAs due to increased risk of renal dysfunction and hyperkalemia 6
• Diltiazem and verapamil are contraindicated in HFrEF as they increase risk of worsening 3

Monitoring Requirements:

• Regular surveillance of blood pressure, renal function, and electrolytes is mandatory 2, 1
• If renal function deteriorates substantially during ACE inhibitor therapy, stop treatment 2
• Monitor for hyperkalemia closely when using MRAs, especially in patients with chronic kidney disease 3

Beta-Blocker Specific Warnings:

• Absolute contraindications include asthma, severe bronchial disease, symptomatic bradycardia or hypotension 6
• If inotropic support is needed in a patient on beta-blockade, use phosphodiesterase inhibitors as their effects are not antagonized by beta-blockers 2, 6

Special Populations

Heart Failure with Preserved Ejection Fraction (HFpEF, LVEF ≥50%):

• SGLT2 inhibitors are the cornerstone of HFpEF treatment, reducing cardiovascular death and heart failure hospitalization 1, 6

Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF, LVEF 41-49%):

• Treat similarly to HFrEF with the same four-drug foundational therapy 6