What are the indications for Ivabradine (Ivabradine)?

From the Guidelines

Ivabradine is indicated for patients with symptomatic (NYHA class II-III) stable chronic heart failure with reduced ejection fraction (HFrEF) (LVEF ≤35%) who are in sinus rhythm with a resting heart rate of 70 bpm or greater at rest, despite receiving guideline-directed medical therapy (GDMT) including a beta blocker at maximum tolerated dose. This recommendation is based on the most recent and highest quality study available, which demonstrated the efficacy of ivabradine in reducing heart failure hospitalization 1.

Key Considerations

• Ivabradine works by selectively inhibiting the If current in the sinoatrial node, providing heart rate reduction without affecting blood pressure, contractility, or intracardiac conduction.
• The typical starting dose is 5 mg twice daily, which can 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.
• Common side effects include visual disturbances (phosphenes), bradycardia, and atrial fibrillation, so regular monitoring of heart rhythm is necessary during treatment.
• Ivabradine is contraindicated in patients with persistent or chronic atrial fibrillation, those experiencing 100% atrial pacing, or unstable patients.

Clinical Context

• Ivabradine is an adjunctive means to reduce the heart rate in patients with chronic HFrEF who are in sinus rhythm.
• Benefits of ivabradine were noted especially for those patients with contraindications to beta-blockers, on beta-blocker doses <50% of GDMT targets, and with resting heart rate ≥77 beats/min at study entry.
• A history of paroxysmal AF is not a contraindication to ivabradine; in the SHIFT study, nearly 10% of patients had a history of paroxysmal AF, with a requirement for sinus rhythm at least 40% of the time 1.

Guideline Recommendations

• The 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment recommends ivabradine as a Class IIa, Level of Evidence: B-R therapy to reduce the risk of HF hospitalization in patients with HFrEF (LVEF ≤35%) already receiving GDMT, including a beta-blocker at the maximally tolerated dose, and who are in sinus rhythm with a heart rate greater than 70 beats/min at rest 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Heart Failure in Adult Patients 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. ( 1.1)

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.

The indications for Ivabradine are:

• 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 2, 2, 2. Key points:
• The patient should have a left ventricular ejection fraction ≤ 35% 2.
• The patient should be 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 2.

From the Research

Indications for Ivabradine

• Ivabradine is indicated for the treatment of adults with New York Heart Association class II-IV chronic heart failure with systolic dysfunction, in sinus rhythm, with a heart rate of ≥75 beats per minute (bpm) 3.
• It is also used in patients with heart failure with reduced ejection fraction (HFrEF) who have a resting heart rate ≥70 bpm, despite receiving optimal beta-blocker therapy 4, 5.
• The European Society of Cardiology and American College of Cardiology/American Heart Association guidelines recommend ivabradine for symptomatic heart failure patients (NYHA ≥2) with ejection fraction 35% or less, sinus rhythm, and heart rate at least 70 bpm, despite maximally titrated β-blocker therapy 5.
• Ivabradine may also be considered for patients with heart failure with preserved ejection fraction (HFpEF) who have a resting heart rate ≥75 bpm in sinus rhythm, although the association between heart rate reduction and left ventricular diastolic function in these patients remains uncertain 6.

Patient Selection

• Patients with chronic systolic heart failure who are not on optimal beta-blocker therapy due to intolerance or contraindications may be eligible for ivabradine treatment 5.
• Patients with HFrEF who have a resting heart rate ≥70 bpm, despite receiving optimal beta-blocker therapy, may also be eligible for ivabradine treatment 4, 5.
• The indication for ivabradine treatment is around 17% in a carefully managed population of patients with moderate and stable HFrEF, in which optimal guideline-directed medical therapy is properly attained 5.

Clinical Benefits

• Ivabradine has been shown to reduce the combined endpoint of cardiovascular death and hospitalization for worsening heart failure in patients with HFrEF 3, 4, 7.
• It also improves left ventricular ejection fraction, reduces left ventricular remodeling, and increases exercise capacity in patients with HFrEF 7.
• However, ivabradine has no significant effect on quality of life or cardiovascular mortality in these patients 7.