What is the primary treatment for stage C heart failure?

Primary Treatment for Stage C Heart Failure

The primary treatment for Stage C heart failure with reduced ejection fraction (HFrEF) consists of quadruple guideline-directed medical therapy (GDMT): an ACE inhibitor/ARB/ARNI, a beta-blocker (bisoprolol, carvedilol, or metoprolol succinate), a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor, initiated simultaneously or in rapid sequence at low doses and uptitrated to target, plus diuretics for fluid management. 1

Core Pharmacologic Therapy for HFrEF (LVEF ≤40%)

Four Pillars of GDMT - Start Simultaneously

Step 1: Initiate all four medication classes together at low doses rather than waiting to achieve target dosing before starting the next medication 1:

• ARNI (sacubitril/valsartan) is the preferred renin-angiotensin system inhibitor for NYHA class II-III symptoms to reduce morbidity and mortality 1

  • If ARNI is not feasible, use an ACE inhibitor as the alternative 1
  • If ACE inhibitor causes cough or angioedema and ARNI is not feasible, use an ARB 1

• Beta-blocker (one of three proven to reduce mortality): bisoprolol, carvedilol, or sustained-release metoprolol succinate for all patients with current or previous symptoms 1

• MRA (spironolactone or eplerenone) for NYHA class II-IV symptoms if eGFR >30 mL/min/1.73 m² and potassium <5.0 mEq/L 1

• SGLT2 inhibitor for all patients regardless of diabetes status to reduce hospitalizations and cardiovascular mortality 1

Step 2: Diuretics for Symptom Management

• Loop diuretics are essential when fluid overload manifests as pulmonary congestion or peripheral edema, providing rapid improvement in dyspnea and exercise tolerance 1, 2
• Always combine diuretics with the four-pillar GDMT regimen 1
• Avoid thiazides if eGFR <30 mL/min unless used synergistically with loop diuretics 2

Step 3: Uptitration Strategy

• Increase doses to target levels proven effective in clinical trials, not based solely on symptomatic improvement 2
• Uptitration can proceed without achieving target dose of one medication before increasing another 1
• Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, then every 6 months 2

Treatment for HFmrEF (LVEF 41-49%)

• SGLT2 inhibitors are beneficial for decreasing HF hospitalizations 1
• Continue GDMT if the patient previously had HFrEF and improved to HFmrEF 1
• MRAs (particularly spironolactone) may be considered, especially for patients on the lower end of this EF spectrum 1
• Diuretics as needed for volume management 1

Treatment for HFpEF (LVEF ≥50%)

• SGLT2 inhibitors are beneficial in decreasing HF hospitalizations and cardiovascular mortality 1
• Blood pressure control to published guideline targets using ACE inhibitors, ARBs, or beta-blockers 1
• Diuretics for relief of symptoms due to volume overload 1
• MRAs may be considered to decrease hospitalizations, particularly in patients with LVEF on the lower end of the preserved spectrum 1
• ARBs may be considered to decrease hospitalizations 1
• Atrial fibrillation management according to guidelines can improve symptoms 1

Critical Implementation Points

Initiation Timing and Sequence

• Start GDMT simultaneously or in rapid sequence at the time of HF diagnosis, including during hospitalization 3
• Do not delay initiation waiting for "stability" - early initiation provides substantial absolute risk reduction 3
• All four medication classes can be started together at initial low doses 1

Common Pitfalls to Avoid

• Never discontinue GDMT even if symptoms resolve and EF improves - 40% of patients relapse within 6 months of medication withdrawal 1
• Avoid NSAIDs as they interfere with ACE inhibitor efficacy 2
• Avoid potassium-sparing diuretics during ACE inhibitor initiation 1, 2
• Avoid calcium channel blockers with negative inotropic effects (non-dihydropyridines) if EF <50% 2
• Review and potentially reduce diuretics for 24 hours before initiating ACE inhibitors to avoid excessive hypotension 1, 2

Monitoring Requirements

• If renal function deteriorates substantially, stop ACE inhibitor treatment 1, 2
• Temporary dose adjustments may be needed during acute non-cardiac illnesses (respiratory infections, dehydration risk) 1
• Educate patients against spontaneous discontinuation without discussion 1

Device Therapy Considerations

For eligible patients with HFrEF on optimal GDMT 1:

• ICD for primary prevention if LVEF ≤35% and NYHA class II-III (or LVEF ≤30% and NYHA class I) at least 40 days post-MI with expected survival >1 year
• CRT if LVEF ≤35%, sinus rhythm, LBBB with QRS ≥150 ms, and NYHA class II-IV symptoms

Special Populations

HF with Improved EF (HFimpEF)

• Continue all GDMT indefinitely to prevent relapse of HF and LV dysfunction, even in asymptomatic patients 1
• Withdrawal of medications results in 40% relapse rate within 6 months 1

Patients with Diabetes

• SGLT2 inhibitors are particularly beneficial for reducing HF hospitalization risk in diabetic patients with established cardiovascular disease or stage B HF 1
• GLP-1 receptor agonists with proven cardiovascular benefit may be added for patients with type 2 diabetes, obesity, and symptomatic HFpEF to reduce symptoms and improve exercise function 1

1, 2, 4, 3