What is the recommended dosage and treatment regimen for Ivabradine (Ivabradine) in patients with heart failure or inappropriate sinus tachycardia?

Ivabradine Dosing and Treatment Regimen

For heart failure with reduced ejection fraction (HFrEF), start ivabradine at 5 mg twice daily with meals in patients already on maximally tolerated beta-blockers who remain in sinus rhythm with resting heart rate ≥70 bpm, then titrate to 7.5 mg twice daily after 2 weeks if heart rate remains >60 bpm. 1

Heart Failure Dosing Algorithm

Initial Dosing

• Standard starting dose: 5 mg twice daily with meals for patients on maximally tolerated beta-blockers with persistent resting heart rate ≥70 bpm 2, 1
• Reduced starting dose: 2.5 mg twice daily for patients with history of conduction defects, age ≥75 years, or those in whom bradycardia could lead to hemodynamic compromise 2, 1

Dose Titration (After 2 Weeks)

The FDA label provides clear titration guidance based on heart rate response 1:

• 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 (target achieved)
• Heart rate <50 bpm or symptomatic bradycardia: Decrease by 2.5 mg twice daily; discontinue if already on 2.5 mg twice daily

Critical Prerequisites for HFrEF

Ivabradine should only be initiated when ALL of the following criteria are met 2:

• Left ventricular ejection fraction ≤35%
• Stable, symptomatic chronic heart failure (NYHA class II-III)
• Sinus rhythm present (not persistent/chronic atrial fibrillation)
• Resting heart rate ≥70 bpm
• Already receiving guideline-directed medical therapy including beta-blocker at maximally tolerated dose

Important caveat: The 2021 ACC guidelines emphasize that beta-blockers should be optimized FIRST before adding ivabradine, as beta-blockers have mortality benefits while ivabradine reduces hospitalizations but not mortality 2. A history of paroxysmal atrial fibrillation is acceptable if sinus rhythm is present ≥40% of the time 2.

Inappropriate Sinus Tachycardia (IST) Dosing

Initial Dosing

• Standard dose: 2.5-7.5 mg twice daily based on symptom severity and heart rate response 2
• The ACC/AHA/HRS guidelines note a dosing range of 2.5 to 7.5 mg twice daily was effective in clinical trials 2

Treatment Approach

Ivabradine is a Class IIa recommendation (reasonable option) for symptomatic IST according to the 2015 ACC/AHA/HRS supraventricular tachycardia guidelines 2. The evidence shows:

• Significant heart rate reduction from baseline 98.4±11.2 to 84.7±9.0 bpm (p<0.001) 2
• Improved exercise tolerance and symptom resolution in many patients 2
• Superior efficacy compared to metoprolol in observational studies 2
• Persistent clinical benefit observed in some patients even after discontinuation 2, 3

Beta-blockers may be combined with ivabradine (Class IIb recommendation) for refractory IST, though close monitoring for excessive bradycardia is essential 2.

Absolute Contraindications

The FDA label specifies the following contraindications 1:

• Acute decompensated heart failure
• Blood pressure <90/50 mm Hg
• Sick sinus syndrome, sinoatrial block, or 3rd-degree AV block (without pacemaker)
• Severe hepatic impairment
• Pacemaker dependence (heart rate maintained exclusively by pacemaker)
• Concomitant strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir, etc.)

Safety Monitoring

Common Adverse Effects

• Phosphenes (visual brightness phenomena): Occur in 3-15% of patients, usually transient and self-limited 2, 3
• Bradycardia: Monitor heart rate regularly; occurred in 6.0% per patient-year in SHIFT trial 1
• Atrial fibrillation: Increased risk (5.0% vs 3.9% per patient-year with placebo); requires regular rhythm monitoring and discontinuation if AF develops 1

Drug Interactions

Avoid strong CYP3A4 inhibitors and inducers 2, 1:

• Inhibitors (contraindicated): Ketoconazole, itraconazole, clarithromycin, ritonavir, nelfinavir
• Inducers (avoid): Carbamazepine, phenytoin, rifampin, St. John's wort
• Use caution with diltiazem, verapamil, and grapefruit juice 2

Duration of Therapy

For HFrEF: Ivabradine is intended for long-term use as part of guideline-directed medical therapy, with ongoing monitoring of heart rate and rhythm 2.

For IST: Treatment duration varies; some patients achieve persistent symptom control even after discontinuation, while others require ongoing therapy 3. Research suggests that 80% of IST patients maintained normal heart rates after stopping ivabradine following 1 year of treatment 4.