Ivabradine in Heart Failure and Inappropriate Sinus Tachycardia
Ivabradine is indicated for patients with symptomatic (NYHA class II-III) stable chronic heart failure with LVEF ≤35% who are in sinus rhythm with a resting heart rate ≥70 bpm and already receiving guideline-directed medical therapy, including beta-blockers at maximum tolerated doses. 1, 2
Indications for Heart Failure
Patient Selection Criteria
- LVEF ≤35%
- Symptomatic heart failure (NYHA class II-III)
- Sinus rhythm (not atrial fibrillation)
- Resting heart rate ≥70 bpm
- Already on guideline-directed medical therapy (GDMT)
- Either on maximally tolerated beta-blocker dose or have contraindication to beta-blockers 1
Clinical Evidence
Ivabradine's benefit in heart failure was established in the SHIFT trial, which demonstrated:
- 18% reduction in the composite endpoint of cardiovascular death or heart failure hospitalization
- Primary benefit driven by reduction in heart failure hospitalizations
- Greatest benefit observed in patients with baseline heart rate ≥75 bpm 3, 4
Dosing Strategy for Heart Failure
Initial Dosing
- Standard starting dose: 5 mg twice daily with meals 2
- For patients ≥75 years or with history of conduction defects: 2.5 mg twice daily 3, 2
Dose Titration
- Assess after 2 weeks of therapy
- Adjust dose to achieve resting heart rate between 50-60 bpm
- Maximum dose: 7.5 mg twice daily
- If heart rate <50 bpm or signs of bradycardia develop: decrease dose by 2.5 mg twice daily 2
Monitoring
- Regular cardiac rhythm monitoring is essential due to 5% risk of atrial fibrillation per patient-year
- Discontinue if atrial fibrillation develops 3
- Monitor for visual side effects (phosphenes) and bradycardia 3, 4
Use in Inappropriate Sinus Tachycardia
While not an FDA-approved indication, evidence suggests ivabradine may be beneficial for inappropriate sinus tachycardia:
- Can be used in patients who have failed or cannot tolerate conventional therapy
- Dosing: 5-7.5 mg twice daily (similar to heart failure dosing)
- Shown to reduce maximum and mean heart rate without significantly affecting minimum heart rate 5
- May prevent inappropriate ICD shocks due to sinus tachycardia 6
Important Considerations and Contraindications
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 2
Common Adverse Effects
- Symptomatic bradycardia (2.7% of patients)
- Visual disturbances/phosphenes (3% of patients)
- Atrial fibrillation (5% per patient-year) 3, 4
Clinical Pearls
- Beta-blockers should be optimized before initiating ivabradine due to their proven mortality benefits
- Only 25% of patients in the SHIFT trial were on optimal beta-blocker doses, highlighting the importance of beta-blocker optimization first 1
- Ivabradine provides heart rate reduction without negative inotropic or blood pressure-lowering effects, making it valuable when beta-blockers cannot be maximized 7
By following these guidelines for patient selection and dosing, ivabradine can effectively reduce hospitalizations and improve outcomes in appropriate heart failure patients.