What is the recommended dosage and usage of Ivabradine (Ivabradine) for treating tachycardia?

Ivabradine Dosage and Usage for Tachycardia

For heart failure with reduced ejection fraction (HFrEF), start ivabradine at 5 mg twice daily with food in patients with LVEF ≤35%, sinus rhythm, resting heart rate ≥70 bpm, and who are already on maximally tolerated beta-blocker therapy; for inappropriate sinus tachycardia (IST), ivabradine is the preferred initial pharmacologic agent at 2.5-5 mg twice daily, titrating to 7.5 mg twice daily based on heart rate response. 1, 2, 3, 4

Heart Failure with Reduced Ejection Fraction (HFrEF)

Patient Selection Criteria

• LVEF ≤35% with symptomatic chronic heart failure (NYHA class II-III) 1
• Sinus rhythm with resting heart rate ≥70 bpm despite maximally tolerated beta-blocker therapy 1
• Patients must be stable on guideline-directed medical therapy (GDMT) for at least 4 weeks before initiating ivabradine 1
• History of heart failure hospitalization within the preceding 12 months strengthens the indication 1

Dosing Algorithm for HFrEF

Starting dose: 5 mg twice daily with food 4

Dose adjustment after 2 weeks based on resting heart rate: 4

• 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/symptoms of bradycardia: Decrease by 2.5 mg twice daily; if already on 2.5 mg twice daily, discontinue therapy

Special populations requiring lower starting dose (2.5 mg twice daily): 1, 4

• History of conduction defects (1st or 2nd degree AV block, bundle branch block)
• Age ≥75 years
• Patients at risk for hemodynamic compromise from bradycardia

Critical Prerequisite: Beta-Blocker Optimization

Beta-blockers must be uptitrated to target doses before considering ivabradine because only 25% of patients in the SHIFT trial were on optimal beta-blocker doses, yet beta-blockers have well-proven mortality benefits that ivabradine does not replicate. 1 Ivabradine's primary benefit is reducing heart failure hospitalizations, not mortality. 1

Inappropriate Sinus Tachycardia (IST)

Mandatory First Step: Exclude Reversible Causes

Before prescribing ivabradine, rule out: 3

• Hyperthyroidism, anemia, dehydration
• Infection/fever, exogenous substances (caffeine, stimulants)
• Pain and anxiety disorders
• Focal atrial tachycardia, sinus node reentrant tachycardia, postural orthostatic tachycardia syndrome (POTS)

Diagnostic confirmation requires: 3

• Resting heart rate >100 bpm
• Average 24-hour heart rate >90 bpm
• Sinus tachycardia unexplained by physiological demands
• Associated debilitating symptoms

Why Ivabradine is Preferred for IST

Ivabradine is the preferred initial pharmacologic therapy for symptomatic IST because it selectively reduces heart rate without affecting blood pressure, myocardial contractility, or causing the hypotension commonly seen with beta-blockers and calcium channel blockers. 2, 3 This is particularly valuable since IST predominantly affects young women who often cannot tolerate conventional therapies. 3, 5

Dosing Algorithm for IST

Starting dose: 2.5-5 mg twice daily with food 3

Titration: Up to 7.5 mg twice daily based on heart rate response and symptom control 6, 3

Expected effects: 3, 7, 8

• Reduces daytime heart rate by approximately 14-20 bpm
• Significantly improves exercise tolerance and symptoms
• In randomized trials, 47% of patients experienced complete symptom elimination 8
• Some patients maintain benefit even after discontinuing the drug 6, 7

Alternative and Combination Therapy

• Beta-blockers may be considered but have modest efficacy and tolerability limitations 3
• Combination therapy with ivabradine and metoprolol can be used for refractory cases 3
• Radiofrequency ablation should only be considered for highly symptomatic patients who fail medical therapy, given high recurrence rates and significant complications 3

Mechanism of Action and Unique Properties

Ivabradine selectively inhibits the If current in the sinoatrial node, reducing heart rate by slowing diastolic depolarization without any hemodynamic effects. 2, 3 Unlike beta-blockers or calcium channel blockers:

• No effect on blood pressure—blood pressure may slightly increase with ivabradine use 2
• No negative inotropic effects 3
• No effect on ventricular repolarization 3

This makes ivabradine uniquely valuable when beta-blocker optimization is limited by hypotension in HFrEF patients. 2

Absolute Contraindications

Do not prescribe ivabradine in patients with: 4

• Acute decompensated heart failure
• Atrial fibrillation (ivabradine only works in sinus rhythm) 1, 2, 4
• Clinically significant hypotension or blood pressure <90/50 mmHg 6, 4
• Sick sinus syndrome, sinoatrial block, or 3rd degree AV block without a functioning pacemaker 4
• Pacemaker dependence (heart rate maintained exclusively by pacemaker) 4
• Severe hepatic impairment 2, 6, 4
• Pregnancy (causes fetal toxicity and cardiac teratogenic effects) 2, 4
• Concomitant use of strong CYP3A4 inhibitors (ketoconazole, clarithromycin, nefazodone, ritonavir) 2, 4

Safety Profile and Adverse Effects

Ivabradine has an excellent safety profile demonstrated in large randomized trials involving over 17,000 patients. 2, 3

Common adverse effects: 1, 2, 3

• Phosphenes (visual brightness phenomena): Occur in 3-15% of patients, usually transient, rarely require discontinuation
• Bradycardia: Rate of 6.0% per patient-year in HFrEF trials (2.7% symptomatic, 3.4% asymptomatic) 4
• Atrial fibrillation: Increased risk (5.0% vs 3.9% per patient-year with placebo); regularly monitor cardiac rhythm and discontinue if atrial fibrillation develops 4

Risk factors for bradycardia: 4

• Sinus node dysfunction
• Conduction defects
• Ventricular dyssynchrony
• Concomitant use of other negative chronotropes (digoxin, diltiazem, verapamil, amiodarone)

Monitoring During Treatment

Regular assessment required: 6

• Heart rate response at 2 weeks, then as needed 4
• Cardiac rhythm monitoring to detect atrial fibrillation 4
• Avoid in decompensated heart failure 6

Clinical Pearls

• For IST, treatment is for symptom reduction only—IST has a benign prognosis, so treatment may not be necessary in asymptomatic patients 3
• Lowering heart rate may not always alleviate symptoms in IST patients 3
• In HFrEF, ivabradine provides dose-dependent heart rate reduction of approximately 6-10 bpm at therapeutic doses 2
• Persistent clinical benefit may occur in some IST patients even after discontinuing ivabradine, with 80% maintaining normal heart rate limits after 1 year of treatment 7