When is Ivabradine (Ivabradine) indicated for patients with heart failure and what is the typical starting dose?

Ivabradine in Heart Failure Management

Ivabradine is indicated for patients with stable, symptomatic chronic heart failure with LVEF ≤35%, who are in sinus rhythm with resting heart rate ≥70 beats per minute, and are either on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use, with a recommended starting dose of 5 mg twice daily with food. 1

Patient Selection Criteria

• LVEF ≤35%
• Symptomatic heart failure (NYHA class II-III)
• Sinus rhythm (not atrial fibrillation)
• Resting heart rate ≥70 bpm
• Already receiving guideline-directed medical therapy (GDMT)
• Prior heart failure hospitalization within the past 12 months 2, 3

Dosing Protocol

• Initial dose: 5 mg twice daily with food 1
• Special populations: Start at 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
• Dose adjustment (after 2 weeks):
  • If heart rate >60 bpm: Increase by 2.5 mg twice daily up to maximum 7.5 mg twice daily
  • If heart rate 50-60 bpm: Maintain current dose
  • If heart rate <50 bpm or symptomatic bradycardia: Decrease by 2.5 mg twice daily; discontinue if already at lowest dose 1
• Target: Resting heart rate between 50-60 bpm 1

Clinical Evidence

The SHIFT trial demonstrated an 18% reduction in the composite endpoint of cardiovascular death or heart failure hospitalization with ivabradine therapy (HR 0.82,95% CI 0.75-0.90, p<0.0001) 4. The benefit was primarily driven by:

• Reduction in heart failure hospitalizations (16% with ivabradine vs 21% with placebo; HR 0.74) 4
• Reduction in deaths due to heart failure (3% with ivabradine vs 5% with placebo; HR 0.74) 4

Important Considerations

Beta-Blocker Optimization

Beta-blockers should be optimized to maximum tolerated doses before initiating ivabradine due to their proven mortality benefits. In the SHIFT trial, only 25% of patients were on optimal beta-blocker doses 2, 3.

Contraindications 1

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

Adverse Effects and Monitoring

• Atrial fibrillation: 5% per patient-year (vs 3.9% with placebo) - discontinue ivabradine if atrial fibrillation develops 3, 1
• Bradycardia: 6% per patient-year (2.7% symptomatic) 1
• Visual disturbances/phosphenes: 3% of patients 3, 4

Monitoring Requirements

• Regular assessment of heart rate
• Cardiac rhythm monitoring for development of atrial fibrillation
• Dose adjustment based on heart rate response
• Monitor for visual disturbances

Ivabradine represents an important addition to heart failure therapy for selected patients, with demonstrated benefits in reducing heart failure hospitalizations when added to standard therapy in patients with elevated heart rates despite optimal medical therapy.