In a patient with chronic left systolic heart failure already on metoprolol succinate extended‑release, spironolactone, dapagliflozin (Farxiga), pantoprazole, metformin extended‑release, and atorvastatin, what medication should replace isosorbide mononitrate?

Discontinue Isosorbide Mononitrate and Optimize Existing Guideline-Directed Medical Therapy

You should discontinue isosorbide mononitrate entirely and focus on optimizing the patient's existing guideline-directed medical therapy (GDMT) rather than replacing it with another medication. 1

Rationale for Discontinuation

Isosorbide mononitrate is not part of evidence-based therapy for heart failure with reduced ejection fraction (HFrEF). 1 The 2022 ACC/AHA/HFSA guidelines clearly distinguish between:

• Isosorbide dinitrate plus hydralazine combination - which IS guideline-directed therapy, particularly for self-identified African American patients with HFrEF 1, 2
• Isosorbide mononitrate alone - which has no established role in HFrEF management

The patient is already on the four pillars of GDMT for HFrEF:

• Beta-blocker (metoprolol succinate) 1
• Mineralocorticoid receptor antagonist (spironolactone) 1
• SGLT2 inhibitor (dapagliflozin/Farxiga) 1, 3
• Presumably an ACE inhibitor, ARB, or ARNI (not listed but should be present) 1

What to Do Instead

Focus on uptitrating existing medications to target doses rather than adding new agents. 1 The 2022 guidelines emphasize that titration to target doses shown efficacious in randomized controlled trials reduces cardiovascular mortality and HF hospitalizations. 1

Specific Optimization Steps:

Metoprolol Succinate:

• Current dose: 200 mg daily
• Target dose: 200 mg daily 1
• Action: Already at target - no change needed 1

Spironolactone:

• Current dose: 25 mg daily
• Target dose: 25-50 mg daily 1
• Action: Consider uptitration to 50 mg if tolerated (monitor potassium and renal function closely, keeping serum creatinine ≤2.5 mg/dL in men and potassium <5.0 mEq/L) 1, 2

Dapagliflozin (Farxiga):

• Current dose: 10 mg daily
• Target dose: 10 mg daily 1
• Action: Already at target - no change needed 1, 3

Critical Missing Component

Verify the patient is on an ACE inhibitor, ARB, or ARNI. 1 If not currently prescribed:

• First choice: Sacubitril/valsartan (ARNI) starting at 49/51 mg twice daily, target 97/103 mg twice daily 1
• Alternative: ACE inhibitor (e.g., enalapril 2.5 mg twice daily, target 10-20 mg twice daily) 1
• If ACE inhibitor intolerant: ARB (e.g., valsartan 20-40 mg once daily, target 160 mg twice daily) 1, 2

When Isosorbide Dinitrate/Hydralazine IS Appropriate

The combination of isosorbide dinitrate (not mononitrate) plus hydralazine should be considered if: 1, 2

• Patient self-identifies as African American with NYHA class II-IV symptoms despite optimal GDMT 1, 2
• Persistent symptoms despite maximally tolerated doses of quadruple therapy 1
• Starting dose: 20 mg isosorbide dinitrate + 37.5 mg hydralazine three times daily 1
• Target dose: 40 mg isosorbide dinitrate + 75 mg hydralazine three times daily 1

Common Pitfalls to Avoid

• Do not confuse isosorbide mononitrate with isosorbide dinitrate - only the latter (in combination with hydralazine) has proven mortality benefit in HFrEF 1
• Do not add medications sequentially without uptitrating existing ones - guidelines recommend titration every 1-2 weeks as tolerated to reach target doses 1
• Do not overlook the need for RAS inhibition (ACE-I/ARB/ARNI) - this is foundational therapy with 16-17% relative risk reduction in all-cause mortality 1

Drug Interaction Considerations

The existing medication regimen shows no significant pharmacokinetic interactions. Dapagliflozin does not meaningfully affect metoprolol, spironolactone, metformin, or atorvastatin. 4 Pantoprazole can continue for gastroprotection without adjustment. 4