When is Ivabradine (Ivabrad) indicated and what is the typical dosing regimen?

Ivabradine Indications and Dosing Regimen

Ivabradine 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

Indications

Ivabradine is recommended for patients who meet ALL of the following criteria:

• Stable, symptomatic chronic heart failure (NYHA class II-III)
• Left ventricular ejection fraction (LVEF) ≤35%
• In sinus rhythm (not atrial fibrillation or flutter)
• Resting heart rate ≥70 beats per minute
• Already receiving guideline-directed medical therapy (GDMT)
• Either:
  • On maximally tolerated beta-blocker doses (preferred approach) 2
  • Have contraindications to beta-blocker use 2, 3
• History of heart failure hospitalization within the previous 12 months (preferred) 3

Dosing Regimen

The recommended dosing regimen for ivabradine is:

• Initial dose: 5 mg twice daily with food 1
• Dose adjustment: After 2 weeks, assess heart rate and adjust dose to achieve a resting heart rate between 50-60 beats per minute 3, 1
  • If heart rate >60 bpm: Increase dose by 2.5 mg twice daily up to maximum of 7.5 mg twice daily
  • If heart rate 50-60 bpm: Maintain current dose
  • If heart rate <50 bpm or signs/symptoms of bradycardia: Decrease dose by 2.5 mg twice daily; if current dose is 2.5 mg twice daily, discontinue therapy
• Special populations: Start with 2.5 mg twice daily in:
  • Elderly patients (≥75 years)
  • Patients with history of conduction defects
  • Patients at risk for hemodynamic compromise from bradycardia 3, 1

Mechanism and Benefits

Ivabradine is a selective funny current (If) inhibitor that acts on the sinoatrial node to reduce heart rate without negative inotropic effects 4. Benefits include:

• 18% reduction in composite endpoint of cardiovascular death or heart failure hospitalization 3
• 30% reduction in heart failure hospitalization 3
• Improvement in LVEF (mean increase of 3.24%) 3
• Reduced cardiac remodeling 3, 4
• Improved exercise tolerance and quality of life 3, 4

Contraindications

Ivabradine is contraindicated in patients with:

• Acute decompensated heart failure
• Clinically significant hypotension
• Sick sinus syndrome, sinoatrial block, or 3rd-degree AV block (unless functioning pacemaker present)
• Clinically significant bradycardia
• Severe hepatic impairment
• Pacemaker dependence
• Concomitant use of strong CYP3A4 inhibitors 3, 1
• Atrial fibrillation or flutter 3

Monitoring and Adverse Effects

• Regular monitoring of heart rate and cardiac rhythm
• Common adverse effects include:
  • Bradycardia (6.0% per patient-year; 2.7% symptomatic)
  • Visual disturbances/phosphenes (3% of patients)
  • Atrial fibrillation (5% per patient-year) 3, 1

Important Considerations

• Beta-blockers should be optimized to maximum tolerated doses before initiating ivabradine due to their proven mortality benefits 2, 3
• In real-world practice, only about 17% of heart failure patients may be eligible for ivabradine treatment after optimal GDMT implementation 5
• Discontinue ivabradine if atrial fibrillation develops 1
• Regular cardiac rhythm monitoring is essential during treatment 3, 1

Ivabradine represents an important addition to heart failure therapy for patients who remain symptomatic with elevated heart rates despite optimal standard therapy.