Management of Heart Failure with Reduced Ejection Fraction (HFrEF)

Core Pharmacological Therapy

The American College of Cardiology recommends that all patients with HFrEF should receive four foundational medication classes simultaneously: an ARNI (or ACEi/ARB if ARNI not feasible), a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor, initiated as early as possible even at low doses, with rapid up-titration to target doses within 2 months 1, 2
The American Heart Association suggests ARNI (sacubitril/valsartan) as the preferred first-line agent for patients with NYHA class II-III symptoms to reduce morbidity and mortality 1
If already on ACEi or ARB and tolerating it, the European Society of Cardiology recommends replacing with ARNI to further reduce morbidity and mortality 1
The American College of Cardiology recommends evidence-based beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) for all HFrEF patients unless contraindicated 1, 2
SGLT2 inhibitors (dapagliflozin or empagliflozin) are now Class 1 recommendations for all HFrEF patients regardless of diabetes status, with benefits including once-daily dosing, minimal blood pressure effects, and early onset of benefits 1, 2, 4

The European Journal of Heart Failure suggests starting all four medication classes simultaneously at low doses rather than sequentially achieving target doses of fewer medications, with the goal of achieving optimal treatment within 2 months 1, 2
The American College of Cardiology recommends increasing doses every 1-2 weeks as tolerated, targeting evidence-based doses, and not waiting to achieve target dose of one medication before starting the next 1

The European Journal of Heart Failure states that low blood pressure alone (even <90 mmHg) without symptoms or hypoperfusion is NOT a contraindication to GDMT, and patients should continue all four GDMT classes unless hemodynamic instability or cardiogenic shock is present 3, 6

The American College of Cardiology recommends starting IV loop diuretics immediately in the emergency department without delay, with an initial IV dose equal to or exceeding the chronic oral daily dose 5

The American Heart Association recommends ICD for primary prevention if LVEF ≤35% despite ≥3 months of optimal GDMT and life expectancy >1 year, and CRT for patients with LVEF ≤35%, NYHA class II-IV, sinus rhythm, and LBBB with QRS ≥150 ms 1

The American College of Cardiology recommends referring to HF specialty team if patients have persistent NYHA class III-IV symptoms despite optimal GDMT, recurrent hospitalizations for HF, need for continuous or intermittent inotropic support, or consideration for advanced therapies (transplant, mechanical circulatory support) 1, 2, 5