Initial Treatment Regimen for Chronic Heart Failure with Reduced Ejection Fraction (HFrEF)

Foundational Triple Therapy

The European Society of Cardiology recommends starting an ACE inhibitor and beta-blocker simultaneously in all symptomatic HFrEF patients to reduce cardiovascular death and heart failure hospitalization (Class I, Level A recommendation) 1, 2
The European Society of Cardiology suggests beginning with low doses and titrating upward every 2-4 weeks to target maintenance doses proven effective in clinical trials 1, 3
The European Society of Cardiology recommends an ACE inhibitor initiation protocol that includes reviewing and potentially reducing diuretic dose 24 hours before starting, starting with a low dose, monitoring blood pressure, renal function, and electrolytes, and avoiding NSAIDs and potassium-sparing diuretics during initiation 4
The European Society of Cardiology recommends using evidence-based beta-blocker agents (carvedilol, metoprolol succinate, or bisoprolol) that have demonstrated mortality benefit in HFrEF trials 1, 2

The European Society of Cardiology recommends loop diuretics for all patients with signs or symptoms of fluid overload to improve symptoms and exercise capacity (Class I, Level B) 1, 2
The European Society of Cardiology suggests thiazides can be used if eGFR >30 mL/min, but switching to loop diuretics is recommended below this threshold 4

The European Society of Cardiology recommends replacing ACE inhibitor with sacubitril/valsartan in ambulatory patients who remain symptomatic despite optimal triple therapy to further reduce cardiovascular death and hospitalization (Class I, Level B) 1, 2

The European Society of Cardiology advises against combining ACE inhibitor with ARB and MRA due to increased risk of renal dysfunction and life-threatening hyperkalemia (Class III, Level C) 1, 2
The European Society of Cardiology recommends avoiding diltiazem and verapamil in HFrEF as they worsen heart failure and increase hospitalization risk (Class III, Level C) 1, 2

The European Society of Cardiology recommends checking blood pressure, renal function, and electrolytes at baseline, 1-2 weeks after each medication adjustment, at 3 months, then every 6 months 4
The European Society of Cardiology advises against excessive diuresis before initiating ACE inhibitors, as volume depletion increases hypotension and acute kidney injury risk 4

The European Society of Cardiology recommends implantable cardioverter-defibrillator (ICD) for primary prevention in patients with LVEF ≤35% despite ≥3 months of optimal medical therapy, NYHA Class II-III, and expected survival >1 year (Class I, Level A for ischemic cardiomyopathy, Level B for dilated cardiomyopathy) 1
The European Society of Cardiology advises against implanting ICD within 40 days of myocardial infarction as it does not improve prognosis during this period (Class III, Level A) 1
The European Society of Cardiology recommends cardiac resynchronization therapy (CRT) for patients in sinus rhythm with QRS ≥150 msec, LBBB morphology, and LVEF ≤35% despite optimal medical therapy (Class I, Level A) 1

The American College of Cardiology emphasizes attempting optimization of foundational therapies before switching to Entresto, including stable doses of an ACE inhibitor or ARB plus a beta-blocker, in patients with chronic heart failure 5