Is spironolactone (aldosterone antagonist) necessary for a patient with heart failure with preserved ejection fraction (HFpEF) and diabetes?

Isosorbide Mononitrate is the Unnecessary Medication in HFpEF Management

Isosorbide mononitrate 120 mg once daily should be discontinued as it has no proven benefit in heart failure with preserved ejection fraction (HFpEF) and represents an unnecessary medication burden for this patient.

Rationale for Medication Assessment

When evaluating the patient's current medication regimen for HFpEF (ejection fraction 50%) with diabetes, we need to assess each medication's evidence base:

Medications with Strong Evidence in HFpEF:

1. Empagliflozin (10 mg daily)

   • SGLT2 inhibitors have demonstrated significant cardiovascular and renal benefits in patients with diabetes and heart failure
   • Particularly beneficial in this patient with both diabetes and HFpEF
   • Reduces hospitalizations for heart failure and improves symptoms

2. Sacubitril/valsartan (49/51 mg twice daily)

   • ARNI therapy provides renin-angiotensin system blockade which is beneficial in HFpEF
   • Helps control blood pressure and provides neurohormonal modulation
   • Recommended for symptom management in HFpEF

3. Spironolactone (25 mg daily)

   • While initially controversial in HFpEF, more recent evidence supports its use
   • The TOPCAT trial demonstrated that spironolactone decreases heart failure hospitalizations in HFpEF patients 1
   • Particularly beneficial in HFpEF patients with resistant hypertension 2, 3
   • Current guidelines support diuretics, including spironolactone, for symptom relief in HFpEF 4

Medication Without Evidence in HFpEF:

Isosorbide Mononitrate (120 mg daily)

• No evidence supporting nitrate use for mortality or morbidity benefit in HFpEF
• Not recommended in any of the major heart failure guidelines for HFpEF management 4
• May cause unnecessary side effects like headaches and hypotension
• Can potentially worsen exercise capacity in HFpEF patients

Evidence-Based Approach to HFpEF Management

The 2013 ACCF/AHA guidelines 4 specifically outline the following recommendations for HFpEF:

1. Blood pressure control
2. Diuretics for volume overload
3. Management of comorbidities (particularly diabetes)

Notably absent from these recommendations is the use of nitrates like isosorbide mononitrate.

Spironolactone in HFpEF: Why It Should Be Continued

Although spironolactone was initially controversial in HFpEF, more recent evidence supports its use:

• The TOPCAT trial showed benefit in reducing heart failure hospitalizations in the Americas cohort 1
• Particularly effective in HFpEF patients with resistant hypertension 2, 3
• Provides additional benefit beyond just diuresis through anti-fibrotic and anti-remodeling effects
• Current dose of 25 mg daily is appropriate and within guideline recommendations 5

Potential Risks to Monitor

When continuing spironolactone in this patient population:

• Monitor serum potassium and renal function (1-2 weeks after initiation, after dose changes, and periodically thereafter)
• Watch for hyperkalemia, especially with concurrent ARNI therapy
• Consider risk of gynecomastia (affects approximately 10% of male patients)

Conclusion

Based on current evidence and guidelines, isosorbide mononitrate 120 mg daily should be discontinued as it lacks evidence for benefit in HFpEF and adds to medication burden. The patient's other medications (empagliflozin, sacubitril/valsartan, and spironolactone) all have evidence supporting their use in a patient with HFpEF and diabetes and should be continued with appropriate monitoring.