Ivabradine Indication for Heart Failure with Reduced Ejection Fraction
Ivabradine is indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic HFrEF (LVEF ≤35%) who are in sinus rhythm with resting heart rate ≥70 bpm and are either on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use. 1
Specific Patient Criteria
The following criteria must ALL be met before considering ivabradine 2, 3:
- Left ventricular ejection fraction ≤35% 2, 1
- NYHA class II-III symptoms (stable, symptomatic chronic heart failure) 2, 3
- Sinus rhythm (not atrial fibrillation, atrial flutter, or 100% ventricular pacing) 2, 3
- Resting heart rate ≥70 beats per minute 2, 1
- On maximally tolerated beta-blocker dose OR have beta-blocker contraindication 2, 1
- Stable on guideline-directed medical therapy for at least 4 weeks 2, 4
- History of heart failure hospitalization within the preceding 12 months 2
Critical Sequencing: Beta-Blocker Optimization First
Beta-blockers must be optimized to target or maximally tolerated doses before initiating ivabradine, as beta-blockers have proven mortality benefits that ivabradine does not. 2, 3 In the pivotal SHIFT trial, only 25% of patients were on optimal beta-blocker doses, yet the trial still demonstrated benefit—this does not justify skipping beta-blocker optimization. 2, 3
Ivabradine is adjunctive therapy only, not first-line treatment. 3, 4 The primary benefit is reduction in heart failure hospitalizations, not mortality. 2, 3, 5
Absolute Contraindications
Ivabradine must NOT be used in 1, 3:
- Acute decompensated heart failure 1
- Atrial fibrillation or other non-sinus rhythms 2, 3, 4
- Sick sinus syndrome, sinoatrial block, or 3rd-degree AV block (unless functioning demand pacemaker present) 1
- Clinically significant bradycardia or hypotension 1
- Severe hepatic impairment 1, 6
- Heart rate maintained exclusively by pacemaker 1
- Concomitant use with strong CYP3A4 inhibitors 1
- Recent myocardial infarction within 2 months 2, 4
Dosing and Monitoring
Starting dose: 5 mg twice daily with food (2.5 mg for vulnerable adults). 1, 6 After 2 weeks, adjust based on heart rate with a target of 50-60 bpm. 3, 4 Maximum dose is 7.5 mg twice daily. 1
Critical monitoring requirements 3, 4:
- Regularly monitor cardiac rhythm and discontinue immediately if atrial fibrillation develops, as ivabradine increases atrial fibrillation risk (5.0% vs 3.9% per patient-year with placebo) 3
- Monitor for symptomatic bradycardia (occurred in 2.7% of patients) 3
- Assess for visual disturbances (phosphenes) 1
Common Clinical Pitfalls
Do not combine ivabradine with non-dihydropyridine calcium channel blockers (diltiazem, verapamil) due to excessive heart rate lowering and increased ivabradine exposure. 3
Do not use ivabradine in patients with persistent or chronic atrial fibrillation, even if rate-controlled, as it loses efficacy in non-sinus rhythms. 2, 6 Patients with paroxysmal atrial fibrillation may be considered only if in sinus rhythm >60% of the time. 4
Avoid using ivabradine as a substitute for inadequate beta-blocker titration. 2, 3 The evidence shows greater benefit in patients with contraindications to beta-blockers or on beta-blocker doses ≤50% of target with heart rate ≥77 bpm. 2
Expected Clinical Benefit
The primary benefit is 18% relative risk reduction in the composite endpoint of cardiovascular death or heart failure hospitalization, driven entirely by reduction in heart failure hospitalizations, not mortality. 2, 5, 7 Benefits become apparent within 3 months of treatment initiation. 5