General Information

Corlanor (ivabradine) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker. This channel is responsible for the cardiac pacemaker If current, which regulates heart rate.

Corlanor is specifically 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

as an oral solution for the treatment of stable symptomatic heart failure due to dilated cardiomyopathy (DCM) in pediatric patients aged 6 months and older, who are in sinus rhythm with an elevated heart rate

Corlanor is supplied as tablets or as an oral solution.

Adult and pediatric patients greater than 40 kg:

Starting dose is 2.5 (pediatrics and vulnerable adults) or 5 mg twice daily with food. After 2 weeks of treatment, adjust dose based on heart rate. The maximum dose is 7.5 mg twice daily.

Pediatric patients less than 40 kg:

Starting dose is 0.05 mg/kg twice daily with food. Adjust dose at two-week intervals by 0.05 mg/kg based on heart rate. Maximum dose is 0.2 mg/kg (patients 6 months to less than 1 year old) or 0.3 mg/kg (patients 1 year old and older), up to a total of 7.5 mg twice daily.

Mechanism of Action

Corlanor (ivabradine) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If current (If), resulting in heart rate reduction with no effect on ventricular repolarization and no effects on myocardial contractility.

Clinical Trial Results

The FDA approval of Corlanor was based on SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine), a randomized, double-blind trial comparing Corlanor and placebo in 6,558 adults with stable NYHA class II to IV heart failure, left ventricular ejection fraction ≤ 35%, and resting heart rate ≥ 70 bpm. ALl enrolled subjects had been clinically stable for at least 4 weeks on an optimized and stable clinical regimen, with fluid retention and symptoms of congestion minimized. Subjects also had been hospitalized for heart failure within 12 months prior to study entry. All subjects were initiated on Corlanor 5 mg (or matching placebo) twice daily and the dose was increased to 7.5 mg twice daily or decreased to 2.5 mg twice daily to maintain the resting heart rate between 50 and 60 bpm, as tolerated. The primary endpoint was a composite of the first occurrence of either hospitalization for worsening heart failure or cardiovascular death. Corlanor reduced the risk of the combined endpoint of hospitalization for worsening heart failure or cardiovascular death based on a time-to-event analysis. The treatment effect reflected only a reduction in the risk of hospitalization for worsening heart failure; there was no favorable effect on the mortality component of the primary endpoint. In the overall treatment population, Corlanor had no statistically significant benefit on cardiovascular death.