What additional medication should be prescribed upon discharge for a patient with heart failure with reduced ejection fraction (HFrEF), hypertension, type 2 diabetes mellitus, and stage 3 chronic kidney disease (CKD), currently on amlodipine, metformin, aspirin, and carvedilol?

Sacubitril/Valsartan is the Optimal Additional Medication for this Patient with HFrEF and CKD

Sacubitril/valsartan (option D) should be prescribed upon discharge for this patient with heart failure with reduced ejection fraction (HFrEF), hypertension, type 2 diabetes mellitus, and stage 3 chronic kidney disease.

Rationale for Sacubitril/Valsartan

Sacubitril/valsartan is the optimal choice for this patient based on several key factors:

1. Guidelines Support: The 2020 ACC/AHA guidelines strongly recommend ARNI therapy (sacubitril/valsartan) as a replacement for ACE inhibitors or ARBs in patients with HFrEF (LVEF ≤40%) to reduce morbidity and mortality 1. This patient has an LVEF of 40%, qualifying him for this therapy.

2. Mortality Benefit: Sacubitril/valsartan has been shown to reduce the composite endpoint of cardiovascular death or heart failure hospitalization by 20% compared to ACE inhibitors 1. Recent clinical evidence also demonstrates reduced all-cause mortality in older patients hospitalized for HFrEF who were prescribed sacubitril/valsartan at discharge 2.

3. Safety in CKD: Despite the patient's stage 3 CKD (eGFR 42 mL/min/1.73 m²), recent research shows no significant difference in eGFR from baseline to 90 days in patients with HF and CKD prescribed sacubitril/valsartan, while demonstrating improvement in ejection fraction 3.

4. Hyperkalemia Management: The patient currently has hyperkalemia (K+ 5.8 mEq/L), and sacubitril/valsartan has been shown to have a reduced risk of hyperkalemia compared to ACE inhibitors when used in heart failure management 1.

Analysis of Alternative Options

A. Empagliflozin

While SGLT2 inhibitors like empagliflozin are recommended for patients with HFrEF 1, 4, and would be beneficial for this patient's diabetes, they should be added to the foundational therapy that includes a renin-angiotensin system inhibitor. The patient is not currently on an ACEi/ARB/ARNI, making sacubitril/valsartan the priority addition.

B. Lisinopril

An ACE inhibitor would typically be appropriate for HFrEF, but guidelines now recommend ARNI therapy over ACE inhibitors when possible 1. Additionally, the patient's hyperkalemia (K+ 5.8 mEq/L) makes an ACE inhibitor less desirable due to its potential to further increase potassium levels.

C. Spironolactone

While MRAs like spironolactone are part of guideline-directed medical therapy for HFrEF, they are contraindicated in this patient due to his significant hyperkalemia (K+ 5.8 mEq/L). Adding spironolactone would substantially increase the risk of worsening hyperkalemia.

Implementation Considerations

1. Dosing: Start with 49/51 mg twice daily and target 97/103 mg twice daily as tolerated 4, 5.

2. Monitoring:

   • Monitor blood pressure closely as sacubitril/valsartan can cause hypotension
   • Check renal function and potassium levels within 1-2 weeks of initiation
   • Watch for signs of angioedema, which is a rare but serious side effect 5

3. Precautions:

   • Ensure the patient has not been on an ACE inhibitor within the past 36 hours before starting sacubitril/valsartan to reduce the risk of angioedema 5
   • Educate the patient about potential side effects including dizziness, cough, and hypotension 5

Comprehensive Treatment Plan

The patient should receive quadruple therapy for HFrEF, which includes:

1. Sacubitril/valsartan (ARNI) - to be added now
2. Carvedilol (beta-blocker) - already prescribed
3. SGLT2 inhibitor (empagliflozin) - consider adding after stabilizing on ARNI
4. MRA (spironolactone) - consider only after resolving hyperkalemia

This approach aligns with current guidelines that recommend these four medication classes to significantly reduce mortality and hospitalizations in patients with HFrEF 1, 4.

Common Pitfalls to Avoid

1. Hyperkalemia Management: Do not add an MRA while the patient has significant hyperkalemia. Address the elevated potassium first.

2. ACE Inhibitor Washout: Ensure adequate washout period (36 hours) if the patient has been on an ACE inhibitor before starting sacubitril/valsartan.

3. Blood Pressure Monitoring: The patient's current BP is 102/59 mmHg, which is relatively low. Start at the lower dose of sacubitril/valsartan and monitor closely for hypotension.

4. Renal Function: While sacubitril/valsartan is safe in CKD, continue to monitor renal function regularly, especially during the initial treatment period.