When is Ivabradine recommended?

Ivabradine Recommendations for Heart Failure Management

Ivabradine is recommended for patients with stable, symptomatic chronic heart failure with reduced ejection fraction (LVEF ≤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 and Patient Selection

• Primary indication: Reduction of hospitalization risk for worsening heart failure 1, 2
• Patient criteria:
  • LVEF ≤35%
  • Stable, symptomatic chronic heart failure (NYHA class II-III)
  • Sinus rhythm (not effective in atrial fibrillation)
  • Resting heart rate ≥70 bpm despite maximally tolerated beta-blocker therapy
  • History of heart failure hospitalization within previous 12 months (preferred) 2, 3

Dosing Protocol

1. Starting dose: 5 mg twice daily with food 1
2. Dose adjustment:
   • Assess after two weeks
   • Target heart rate: 50-60 bpm
   • Maximum dose: 7.5 mg twice daily
   • For elderly patients (≥75 years), patients with conduction defects, or risk for hemodynamic compromise: Start with 2.5 mg twice daily 1, 2

Monitoring Requirements

• Regular assessment of heart rate
• Cardiac rhythm monitoring for development of atrial fibrillation
• Dose adjustment based on heart rate response 2
• Monitor for adverse effects:
  • Bradycardia (6.0% per patient-year; 2.7% symptomatic)
  • Visual disturbances/phosphenes (3% of patients)
  • Atrial fibrillation (5% per patient-year) 1, 2

Clinical Benefits

• 18% reduction in composite endpoint of cardiovascular death or heart failure hospitalization 2, 4
• 30% reduction in heart failure hospitalization 5
• Improvement in LVEF (mean difference +3.24%) 4
• Reduced cardiac remodeling 6
• Improved exercise tolerance and quality of life 6

Contraindications

• 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 1
• Atrial fibrillation or flutter 2

Important Considerations

• Beta-blockers should be optimized to maximum tolerated doses before initiating ivabradine due to their proven mortality benefits 2, 3
• Greatest benefit observed in patients with baseline heart rate ≥75 bpm 5
• Discontinue ivabradine if atrial fibrillation develops 1
• No significant drug interactions with statins 3
• May be considered in patients with contraindications to beta-blockers (Class IIa recommendation) 3

Common Adverse Effects

• Bradycardia (asymptomatic and symptomatic)
• Visual disturbances (phosphenes)
• Atrial fibrillation 4, 1

Ivabradine provides a valuable addition to heart failure therapy by reducing heart rate without negative inotropic effects or blood pressure reduction, making it particularly useful for patients who cannot tolerate optimal beta-blocker doses or who remain symptomatic with elevated heart rates despite optimal therapy.