What medication should be added to a patient with heart failure with reduced ejection fraction (HFrEF) and a heart rate of tachycardia, already on metoprolol succinate (beta-blocker), to reduce the risk of heart failure hospitalizations?

Ivabradine is the Most Appropriate Addition to Reduce Heart Failure Hospitalizations

Ivabradine should be added to JT's medication regimen to reduce his risk of heart failure hospitalizations, given his elevated heart rate of 85 beats/min despite being on a maximal dose of beta-blocker therapy.

Rationale for Selecting Ivabradine

Ivabradine is specifically indicated for patients who match JT's clinical profile:

• LVEF ≤35% (JT has LVEF of 25%)
• Symptomatic heart failure (JT has NYHA Class II symptoms)
• Sinus rhythm with resting heart rate ≥70 beats/min (JT has heart rate of 85 beats/min)
• On maximally tolerated beta-blocker therapy (JT is on metoprolol succinate 200 mg daily) 1

The FDA-approved indication for ivabradine clearly states it is indicated "to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤35%, who are in sinus rhythm with resting heart rate ≥70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use" 1.

Analysis of Treatment Options

Ivabradine

• Specifically targets elevated heart rate by inhibiting the funny current (If) in the sinoatrial node
• Reduces heart rate without negative inotropic effects or blood pressure lowering 2
• Reduces HF hospitalizations by 30% in patients with heart rate ≥75 bpm 2
• Optimal heart rate achieved with ivabradine appears to be between 50-60 bpm 3

Digoxin

• JT has a documented allergy to digoxin (rash)
• While digoxin can be beneficial in reducing HF hospitalizations 4, it is absolutely contraindicated due to JT's allergy

Finerenone

• While finerenone is a newer mineralocorticoid receptor antagonist, JT is already on spironolactone 25 mg daily
• Adding a second MRA is not recommended as routine combined use of an ACEI, ARB, and multiple aldosterone antagonists is not recommended for patients with HF and reduced LVEF 4

Hydralazine and Isosorbide Dinitrate

• This combination is primarily recommended for:
  1. African American patients with HF (JT is white)
  2. Patients who cannot tolerate ACEIs/ARBs (JT is already on sacubitril/valsartan)
• Guidelines state this combination "may be reasonable in patients with current or prior symptoms of HF and reduced LVEF who cannot be given an ACEI or ARB because of drug intolerance, hypotension, or renal insufficiency" 4
• JT is already on optimal GDMT including sacubitril/valsartan

Dosing and Monitoring Recommendations

1. Initial dosing: Start ivabradine at 5 mg twice daily with food 1
2. Dose adjustment: Assess after two weeks and adjust dose to achieve resting heart rate between 50-60 bpm
3. Maximum dose: 7.5 mg twice daily 1
4. Monitoring:
   • Regular heart rate monitoring
   • Watch for symptoms of bradycardia
   • Monitor for atrial fibrillation (ivabradine increases risk)

Potential Adverse Effects

• Bradycardia (6.0% per patient-year vs. 1.3% in placebo) 1
• Atrial fibrillation (5.0% per patient-year vs. 3.9% in placebo) 1
• Visual phenomena/phosphenes (luminous phenomena) 1

Important Considerations

• Ivabradine is contraindicated in acute decompensated heart failure, clinically significant hypotension, sick sinus syndrome, sinoatrial block, or 3rd-degree AV block 1
• JT appears to be an ideal candidate for ivabradine as he:
  1. Has stable NYHA Class II symptoms
  2. Has a significantly reduced LVEF (25%)
  3. Has an elevated heart rate (85 bpm) despite maximal beta-blocker therapy
  4. Is already on optimal GDMT (ARNI, beta-blocker, MRA, and SGLT2 inhibitor)

By adding ivabradine to JT's current regimen, we can target his elevated heart rate and potentially reduce his risk of heart failure hospitalizations while maintaining his current comprehensive heart failure therapy.