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 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 betablockers or have a contraindication to beta-blocker use.

Corlanor is supplied as tablets for oral administration. The recommended starting dose is 5 mg twice daily. After 2 weeks of treatment, the dose should be adjusted based on heart rate. The maximum dose is 7.5 mg twice daily. In patients with conduction defects or in whom bradycardia could lead to hemodynamic compromise, initiate dosing at 2.5 mg twice daily.

Clinical Results

FDA Approval

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 (hazard ratio: 0.82, 95% confidence interval [CI]: 0.75, 0.90, p < 0.0001). 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.

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.