Ivabradine Dosing and Usage
For heart failure with reduced ejection fraction (HFrEF), start ivabradine at 5 mg twice daily with food, assess after 2 weeks, and titrate to 7.5 mg twice daily based on heart rate response, targeting a resting heart rate of 50-60 bpm. 1, 2
Patient Selection Criteria for HFrEF
Ivabradine is indicated only for patients meeting ALL of the following criteria:
- Left ventricular ejection fraction ≤35% 1, 2
- NYHA class II-III symptoms (stable, symptomatic chronic heart failure) 1, 3
- Sinus rhythm with resting heart rate ≥70 bpm 1, 2
- On maximally tolerated beta-blocker dose OR have beta-blocker contraindication 1, 2
- NOT in acute decompensated heart failure 3, 2
Dosing Algorithm for HFrEF
Initial Dosing
- Standard patients: 5 mg twice daily with food 1, 2
- Vulnerable patients (history of conduction defects, risk of hemodynamic compromise): 2.5 mg twice daily 2
Dose Titration After 2 Weeks
Adjust based on resting heart rate: 1, 2
- Heart rate >60 bpm: Increase by 2.5 mg twice daily (maximum 7.5 mg twice daily)
- Heart rate 50-60 bpm: Maintain current dose
- Heart rate <50 bpm or symptomatic bradycardia: Decrease by 2.5 mg twice daily; if already on 2.5 mg twice daily, discontinue
Target Dose
- Maximum dose: 7.5 mg twice daily 1, 2
- Target heart rate: 50-60 bpm 2
- Mean achieved dose in trials: 12.8 mg total daily 1
Usage for Inappropriate Sinus Tachycardia (IST)
For IST, ivabradine 5-7.5 mg twice daily is a reasonable option for ongoing management in symptomatic patients who fail or do not tolerate beta-blockers or calcium channel blockers. 3, 4
- Dosing range: 5-7.5 mg twice daily 5, 6
- Efficacy: Reduces mean heart rate by approximately 18-23 bpm and maximal heart rate by 23-39 bpm 5, 6
- Unique benefit: Some patients maintain normal heart rate even after discontinuation (80% in one study) 5
Critical Safety Monitoring
Atrial Fibrillation Risk
Discontinue ivabradine immediately if atrial fibrillation develops. 3, 2
- Ivabradine increases atrial fibrillation risk (5.0% vs 3.9% per patient-year with placebo) 3, 2
- Regularly monitor cardiac rhythm 3, 2
- Ivabradine is ineffective in atrial fibrillation and contraindicated in persistent/chronic atrial fibrillation 3
Bradycardia Monitoring
- Bradycardia occurred in 6.0% per patient-year (2.7% symptomatic) versus 1.3% with placebo 3, 2
- Risk factors: Sinus node dysfunction, conduction defects (1st or 2nd degree AV block), bundle branch block, ventricular dyssynchrony, concurrent negative chronotropes 3, 2
- Not recommended in 2nd degree AV block 2
Absolute Contraindications
Ivabradine is contraindicated in: 2
- Acute decompensated heart failure
- Clinically significant hypotension or bradycardia
- Sick sinus syndrome, sinoatrial block, or 3rd degree AV block (unless functioning pacemaker present)
- Pacemaker-dependent patients (heart rate maintained exclusively by pacemaker)
- Severe hepatic impairment
- Concomitant strong CYP3A4 inhibitors (ketoconazole, clarithromycin, nefazodone, ritonavir, nelfinavir)
Critical Clinical Pitfalls
Beta-Blocker Optimization First
Ivabradine is NOT first-line therapy—beta-blocker optimization must occur before considering ivabradine. 3
- Beta-blockers have proven mortality benefits; ivabradine does not 3
- Only 25% of SHIFT trial patients were on optimal beta-blocker doses 3
- Ivabradine's benefit is driven entirely by reduction in HF hospitalization, not mortality 3
Drug Interactions to Avoid
Avoid combining ivabradine with non-dihydropyridine calcium channel blockers (diltiazem, verapamil). 3
- This combination causes excessive heart rate lowering and increased ivabradine exposure 3
- Avoid all strong CYP3A4 inhibitors and inducers 2
Common Adverse Effects
- Phosphenes (visual brightness): Occur in 3-15% of patients, usually transient 4, 6
- Bradycardia: Most common cardiovascular adverse event 7
- Hypertension and atrial fibrillation: Each occur in ≥1% of patients 2