Ivabradine Dosage and Usage for Heart Failure and Inappropriate Sinus Tachycardia
For patients with heart failure with reduced ejection fraction (HFrEF), ivabradine should be started at 5 mg twice daily with food and titrated to achieve a resting heart rate between 50-60 beats per minute, with a maximum dose of 7.5 mg twice daily. 1
Heart Failure Indication and Dosing
Patient Selection Criteria
- LVEF ≤35%
- Symptomatic (NYHA class II-III) stable chronic heart failure
- Sinus rhythm with resting heart rate ≥70 bpm
- Already receiving guideline-directed medical therapy (GDMT), including beta-blockers at maximum tolerated dose 2
Dosing Protocol
- Initial dose: 5 mg twice daily with meals
- Special populations:
- Age ≥75 years: Start at 2.5 mg twice daily
- History of conduction defects: Start at 2.5 mg twice daily 2
- Dose adjustment (after 2 weeks):
- Heart rate >60 bpm: Increase by 2.5 mg twice daily up to maximum 7.5 mg twice daily
- Heart rate 50-60 bpm: Maintain current dose
- Heart rate <50 bpm or signs of bradycardia: Decrease by 2.5 mg twice daily; discontinue if on lowest dose 1
Monitoring
- Assess heart rate after 2 weeks of treatment
- Regular cardiac rhythm monitoring (due to 5% risk of atrial fibrillation per patient-year) 1
- Discontinue if atrial fibrillation develops
Inappropriate Sinus Tachycardia Usage
For inappropriate sinus tachycardia (IST), though not an FDA-approved indication:
- Dosage range: 5-7.5 mg twice daily
- Can be used as monotherapy or in addition to beta-blocker therapy 3, 4
- Studies show significant reduction in maximum and mean heart rates in IST patients
- Treatment has shown symptomatic improvement in 8 out of 10 patients in clinical studies 3
Efficacy
- In heart failure patients, ivabradine reduces hospitalization for worsening heart failure (16% vs 21% with placebo) 5
- Reduction in cardiovascular death or heart failure hospitalization by 18% 6
- Greatest benefit seen in patients with baseline heart rate ≥75 bpm 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
Common Side Effects
- Symptomatic bradycardia (5% vs 1% with placebo)
- Visual side effects/phosphenes (3% vs 1% with placebo) 5
- Atrial fibrillation (5% per patient-year vs 3.9% with placebo) 1
Important Clinical Considerations
- Beta-blockers should be optimized before starting ivabradine due to their proven mortality benefits 2
- Only 25% of patients in the SHIFT trial were on optimal beta-blocker doses, highlighting the importance of maximizing beta-blocker therapy first 2
- Ivabradine works by selectively inhibiting the If current in the sinoatrial node, providing heart rate reduction without affecting contractility or blood vessels 6
- For IST patients, some studies suggest that symptoms may not return after discontinuation in a significant portion of patients (80% remained in normal heart rate limits) 4
Always ensure patients are in sinus rhythm before initiating therapy, as ivabradine is ineffective in patients with atrial fibrillation or other non-sinus rhythms.