What is the best approach to manage a adult patient with a history of heart failure with reduced ejection fraction (HFrEF) who is currently on lisinopril (angiotensin-converting enzyme inhibitor) 2.5 mg daily, torsemide (loop diuretic) 40 mg daily, and carvedilol (beta blocker) 25 mg twice a day?

Optimizing HFrEF Therapy: Add SGLT2 Inhibitor and Mineralocorticoid Receptor Antagonist Immediately

This patient is significantly undertreated and requires immediate addition of two critical mortality-reducing medications: an SGLT2 inhibitor (dapagliflozin or empagliflozin) and a mineralocorticoid receptor antagonist (spironolactone or eplerenone), while simultaneously uptitrating the existing suboptimal doses of lisinopril and carvedilol. 1, 2

Critical Assessment of Current Regimen

Your patient is on dangerously low doses of foundational therapies:

• Lisinopril 2.5 mg daily is far below the target dose of 20-40 mg daily proven to reduce mortality 3
• Carvedilol 25 mg twice daily is at target dose for patients <85 kg, which is appropriate 3, 4
• Torsemide 40 mg daily is reasonable for volume management 3
• Missing two entire drug classes that each provide approximately 20% mortality reduction: SGLT2 inhibitors and mineralocorticoid receptor antagonists 1, 2

Immediate Action Plan: Quadruple Therapy Implementation

Step 1: Add Missing Foundational Therapies NOW

Start SGLT2 inhibitor immediately (no titration required):

• Dapagliflozin 10 mg once daily (if eGFR ≥20 mL/min/1.73 m²) OR
• Empagliflozin 10 mg once daily (if eGFR ≥30 mL/min/1.73 m²)
• These reduce cardiovascular death and HF hospitalization regardless of diabetes status, with minimal blood pressure effect 1, 2
• Benefits occur within weeks of initiation 2

Start mineralocorticoid receptor antagonist immediately:

• Spironolactone 12.5-25 mg once daily OR
• Eplerenone 25 mg once daily
• Requires eGFR >30 mL/min/1.73 m² and potassium <5.0 mEq/L 3, 2
• Provides at least 20% mortality reduction and reduces sudden cardiac death 2

Step 2: Uptitrate Lisinopril Aggressively

Current dose of 2.5 mg is grossly inadequate 3:

• Increase to 5 mg daily after 1-2 weeks if tolerated
• Then increase to 10 mg daily after another 1-2 weeks
• Target dose: 20-40 mg once daily 3, 1
• Do NOT stop for asymptomatic hypotension with adequate perfusion 1, 2

Step 3: Consider Switching to ARNI (Sacubitril/Valsartan)

Once ACE inhibitor is optimized, strongly consider switching to ARNI:

• Sacubitril/valsartan provides superior mortality reduction (at least 20% better than ACE inhibitors) 2
• Starting dose: 24/26 mg or 49/51 mg twice daily, target 97/103 mg twice daily 1
• Must wait 36 hours after last ACE inhibitor dose before starting ARNI 2
• ARNI is now preferred over ACE inhibitors for symptomatic HFrEF patients 2

Monitoring Requirements

Check at 1-2 weeks after each medication change 1, 2:

• Blood pressure and heart rate
• Serum creatinine and eGFR
• Serum potassium (especially critical with MRA addition)
• Assess for signs/symptoms of congestion

Acceptable changes during optimization 2:

• Creatinine increases up to 30% above baseline are acceptable and should NOT prompt discontinuation
• Potassium up to 5.5 mEq/L is manageable; consider potassium binders (patiromer) rather than stopping MRA 2
• Asymptomatic hypotension (SBP >80 mmHg with adequate perfusion) should NOT delay therapy 1, 2

Why This Matters: The Mortality Benefit

Current evidence shows that quadruple therapy provides approximately 73% mortality reduction over 2 years 2. Your patient is missing:

• ~20% mortality reduction from SGLT2 inhibitor 1, 2
• ~20% mortality reduction from MRA 2
• Suboptimal benefit from severely underdosed ACE inhibitor 3

Common Pitfalls to Avoid

Never down-titrate or stop GDMT for asymptomatic hypotension 1, 2:

• GDMT medications maintain efficacy and safety even with baseline SBP <110 mmHg 2
• Adverse events occur in 75-85% of HFrEF patients regardless of treatment 2
• Patient education about transient dizziness improves compliance 2

Do not delay initiation of all four medication classes 1, 2:

• Start SGLT2 inhibitor and MRA first since they have minimal blood pressure effects 1
• Then uptitrate ACE inhibitor (or switch to ARNI) 1
• Carvedilol is already at target dose 3, 4

Avoid these medication combinations 2:

• Never combine ACE inhibitor with ARNI (risk of angioedema)
• Avoid triple combination of ACE inhibitor + ARB + MRA (hyperkalemia risk)

Diuretic Management

Torsemide 40 mg is appropriate for volume management 3:

• Titrate to achieve euvolemia (no edema, no orthopnea, no JVD) 2
• Then use lowest dose that maintains euvolemic state 2
• Diuretics provide symptom relief but do NOT reduce mortality 1
• Consider adding metolazone 2.5-10 mg if refractory fluid retention develops 3

Timeline for Optimization

Aggressive uptitration schedule 1, 2:

• Week 0: Add SGLT2 inhibitor + MRA, check labs in 1-2 weeks
• Week 2: Increase lisinopril to 5 mg if tolerated, recheck labs in 1-2 weeks
• Week 4: Increase lisinopril to 10 mg, recheck labs in 1-2 weeks
• Week 6: Increase lisinopril to 20 mg, recheck labs in 1-2 weeks
• Week 8-12: Consider switching to ARNI for superior mortality benefit 2

Target: All four medication classes at target or maximally tolerated doses within 6-12 weeks 1, 5

When to Refer to HF Specialist

Consider referral if 1:

• Persistent symptomatic hypotension (SBP <80 mmHg) preventing GDMT optimization
• Refractory hyperkalemia despite potassium binders
• Persistent symptoms despite optimal medical therapy
• Need for advanced therapies (CRT, ICD, transplant evaluation)