What is the use of Ivabradine (Corlanor)?

From the Guidelines

Ivabradine should be considered for patients with symptomatic heart failure with reduced ejection fraction (HFrEF) who are receiving guideline-directed medical therapy, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of ≥70 bpm at rest, as it can reduce heart failure hospitalizations and improve quality of life. The medication works by selectively inhibiting the "funny" current (If) in the sinoatrial node, which controls heart rhythm, and is typically started at a dose of 5 mg twice daily, which may be adjusted to 2.5-7.5 mg twice daily based on heart rate response, aiming for a resting heart rate between 50-60 beats per minute 1. Some key points to consider when prescribing ivabradine include:

• It is indicated for patients with heart failure who have a left ventricular ejection fraction of 35% or less, are in sinus rhythm with a resting heart rate of 70 beats per minute or higher, and remain symptomatic despite optimal medical therapy 1.
• Common side effects include visual brightness disturbances (phosphenes), bradycardia, and atrial fibrillation.
• It should be taken with meals and is contraindicated in severe liver disease, hypotension, and patients with pacemaker-dependent rhythm.
• Unlike beta-blockers, ivabradine doesn't affect blood pressure or cardiac contractility, making it valuable for patients who cannot tolerate beta-blockers or have low blood pressure. The use of ivabradine has been supported by recent guidelines, including the 2022 AHA/ACC/HFSA guideline for the management of heart failure, which recommends its use for patients with symptomatic stable chronic HFrEF who are receiving guideline-directed medical therapy, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of ≥70 bpm at rest 1.

From the FDA Drug Label

Ivabradine tablets are a prescription medicine used: • to treat adults who have chronic (lasting a long time) heart failure, with symptoms, to reduce their risk of hospitalization for worsening heart failure. The main use of Ivabradine is to treat adults with chronic heart failure to reduce the risk of hospitalization for worsening heart failure 2.

• The indication is for stable, symptomatic chronic heart failure with reduced left ventricular ejection fraction 2.
• Key points to consider when using Ivabradine include:
  • Contraindications: recently worsened heart failure, very low blood pressure, certain heart conditions, slow resting heart rate, certain liver problems, and use of medicines that can increase the effects of Ivabradine 2.
  • Side effects: may cause serious side effects, including harm to an unborn baby, increased risk of irregular or rapid heartbeat, and slower than normal heart rate 2.

From the Research

Ivabradine Overview

• Ivabradine is a selective funny current (If) inhibitor in the sinoatrial node, which slows its firing rate and prolongs diastolic depolarization without a negative inotropic effect 3.
• It is approved for use in the United States as an adjunct therapy for heart rate reduction in patients with heart failure with reduced ejection fraction 4.

Clinical Uses

• Ivabradine has been shown to improve clinical outcomes in patients with heart failure with reduced ejection fraction, including reduced heart failure hospitalization and deaths 3, 5.
• It has also been used to treat inappropriate sinus tachycardia, with significant improvement in symptoms and elimination of symptoms in approximately half of patients 6.
• Ivabradine may also play a role in the treatment of patients with stable ischemic heart disease, although the evidence is conflicting 4.

Mechanism of Action

• Ivabradine works by inhibiting the If current in the sinoatrial node, which reduces the heart rate without affecting myocardial contractility or vascular tone 3, 4.
• This mechanism of action is distinct from beta-blockers and calcium channel blockers, which can have negative inotropic effects 5, 4.

Eligibility and Indications

• Ivabradine is recommended for patients with symptomatic heart failure with reduced ejection fraction, sinus rhythm, and a heart rate of at least 70 bpm, despite maximally titrated beta-blocker therapy 7.
• In a real-life population of patients with systolic heart failure, approximately 17% of patients were eligible for ivabradine treatment 7.

Adverse Effects

• The adverse effects of ivabradine include bradycardia, atrial fibrillation, and visual disturbances 5.
• However, ivabradine avoids the negative inotropic effects observed with beta-adrenoceptor antagonists 5.