What is the indication for Ivabradine (Procoralan)?

From the Guidelines

Ivabradine is used to treat symptomatic inappropriate sinus tachycardia (IST), as well as chronic heart failure and stable angina pectoris in patients who cannot take beta-blockers or as an add-on therapy when beta-blockers alone are insufficient. It works by selectively inhibiting the "funny" current (If) in the sinoatrial node, which slows the heart rate without affecting blood pressure or cardiac contractility. For IST, ivabradine is typically prescribed at a dosage of 2.5 to 7.5 mg twice daily, and has been shown to reduce daytime heart rate and improve exercise tolerance and symptoms 1.

Some key points to consider when using ivabradine include:

• It is reasonable for ongoing management in patients with symptomatic IST, as stated in the 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia 1.
• For heart failure, ivabradine is typically prescribed when patients have a reduced ejection fraction (usually less than 35%) and a resting heart rate of 70 beats per minute or higher despite maximum tolerated beta-blocker therapy, as recommended in the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1.
• The usual starting dose is 5 mg twice daily, which may be adjusted to 2.5-7.5 mg twice daily based on heart rate response.
• Ivabradine should be taken with meals and patients should be monitored for side effects including visual disturbances (phosphenes), bradycardia, and atrial fibrillation.
• It's contraindicated in severe liver disease, hypotension, and certain arrhythmias.
• By reducing heart rate, ivabradine decreases cardiac workload, improves myocardial oxygen supply-demand balance, and has been shown to reduce hospitalizations for worsening heart failure, as noted in the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1.

From the FDA Drug Label

Ivabradine tablets are indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use. Ivabradine is a hyperpolarization-activated cyclic nucleotide-gated channel blocker indicated:

• To reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with reduced left ventricular ejection fraction. Ivabradine is used to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure and reduced left ventricular ejection fraction 2, 2, 2.

From the Research

Uses of Ivabradine

• Ivabradine is used to reduce heart rate in patients with heart failure with reduced ejection fraction 3, 4, 5.
• It is also used as an adjunct therapy for heart rate reduction in patients with heart failure 4.
• Ivabradine has been investigated for its use in stable ischemic heart disease, although the evidence is conflicting 4.
• It may play a role in the treatment of patients with inappropriate sinus tachycardia, who often cannot tolerate beta-blockers and/or calcium channel blockers 3, 4, 6.
• Ivabradine has been associated with reduced cardiac remodeling, reduced heart rate variability, improvement in exercise tolerance, improved heart failure class of New York Heart Association, and better quality of life 5.
• It has also been tried in other conditions, such as cardiogenic shock, and is currently in phase II trial for patients with newly diagnosed multiple organ dysfunction syndrome 5.

Mechanism of Action

• Ivabradine is a selective funny current (If) inhibitor in the sinoatrial node, which slows its firing rate, prolonging diastolic depolarization without a negative inotropic effect 5.
• It reduces heart rate without affecting myocardial contractility or vascular tone 4.
• Ivabradine is a use-dependent inhibitor targeting the sinoatrial node 4.

Off-Label Uses

• Ivabradine has been investigated for its use in several off-label indications, including angina, coronary artery disease, postural orthostatic hypotension, and atrial fibrillation 7.
• Larger clinical trials are needed to solidify the benefit of ivabradine in these areas, although studies indicate benefit in most therapeutic areas explored to date 7.