What is the initial medication of choice for a patient with decompensated Heart Failure with reduced Ejection Fraction (HFrEF), considering I thought it was Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs)?

Initial Medication for Decompensated HFrEF

You're right that ACE inhibitors or ARBs are foundational therapy for HFrEF, but in acute decompensation, intravenous loop diuretics are the initial medication of choice to relieve congestion and improve breathlessness, with ACE/ARB initiation or optimization occurring after stabilization. 1

Immediate Management of Acute Decompensation

First-Line Acute Treatment

• IV loop diuretics are recommended as the initial medication for patients presenting with pulmonary congestion/edema without shock to improve breathlessness and relieve congestion 1
• Symptoms, urine output, renal function, and electrolytes require regular monitoring during diuretic therapy 1
• The primary goal is hemodynamic stabilization before initiating or optimizing chronic oral therapies 2

When Inotropes Are Needed

• Reserve inotropic support (dobutamine 2-20 μg/kg/min or dopamine) for patients with persistent hypoperfusion despite adequate cardiac filling pressures 1
• These agents increase mortality risk and should be used only when absolutely necessary for low cardiac output states 3

Transitioning to Guideline-Directed Medical Therapy

ACE Inhibitors/ARBs: Timing and Approach

• ACE inhibitors (or ARBs if ACE-intolerant) should be started as soon as possible after initial stabilization, with blood pressure and renal function permitting 1
• Begin dose up-titration before discharge and complete titration in the outpatient setting 1
• These medications reduce mortality by 17% and HF hospitalizations by 31% 1

The Four Pillars Framework

Modern HFrEF management requires four foundational medication classes initiated rapidly after stabilization 4, 5:

1. ACE inhibitor/ARB (or preferably ARNI) - Start immediately when blood pressure stable 1
2. Beta-blocker - Initiate after stabilization; can often be continued during decompensation 1
3. Mineralocorticoid receptor antagonist (MRA) - Start early as minimal blood pressure effect allows use even in relatively hypotensive patients 1
4. SGLT2 inhibitor - Add during hospitalization for additional mortality benefit 1, 6

Critical Timing Distinctions

Why Not Start with ACE/ARB in Acute Decompensation?

• Acute pulmonary edema requires immediate decongestion, which ACE/ARBs cannot provide 1
• Starting ACE/ARBs in severely volume-overloaded, hypotensive patients risks worsening hypotension and renal function 1
• The 2012 ESC guidelines explicitly state ACE/ARB initiation occurs "as soon as possible" after addressing acute congestion, not as first-line acute therapy 1

Safe In-Hospital Initiation

• Recent evidence confirms initiating or optimizing all four pillars during hospitalization is both feasible and safe 6
• No significant difference in 30-day mortality between newly initiated patients versus those already on therapy (7.14% vs 5.55%, p=0.74) 6
• Monitor creatinine dynamics closely, as optimization may cause transient increases 6

Common Pitfalls to Avoid

Don't Delay Chronic Therapy Too Long

• While diuretics come first acutely, ACE/ARB and other foundational therapies should begin within days, not weeks 1, 6
• Therapeutic inertia leads to suboptimal dosing and prolonged titration times 5
• The mortality benefit requires achieving target doses, not just token initiation 1

Don't Substitute ARB for ACE Without Reason

• ARBs are "not significantly different" from ACE inhibitors in mortality reduction but should be reserved for ACE-intolerant patients 7
• ARNI (sacubitril/valsartan) is now preferred over both ACE/ARB when patients are stable, reducing mortality by 30% 1
• Never give ARNI within 36 hours of last ACE inhibitor dose due to angioedema risk 1

Blood Pressure Concerns

• MRAs have minimal blood pressure effects and can be started even in relatively hypotensive patients 1
• Beta-blockers should be continued during decompensation in most cases rather than stopped 1
• Systolic BP <100 mmHg is a caution but not absolute contraindication for ARNI 1

Practical Algorithm

Day 1 (Acute Presentation):

• IV loop diuretics for congestion 1
• Continue home beta-blocker if already prescribed 1
• Assess for cardiogenic shock requiring inotropes 1, 3

Days 2-3 (After Initial Diuresis):

• Initiate or optimize ACE inhibitor/ARB 1, 6
• Start MRA if not contraindicated 1, 6
• Begin SGLT2 inhibitor 6

Before Discharge:

• Up-titrate all medications toward target doses 1
• Establish outpatient titration plan 1
• Consider switching ACE/ARB to ARNI after stabilization 1