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FDA Approves Heart Failure Drug Ivabradine (Corlanor)
The FDA has granted approval of ivabradine (Corlanor, Amgen), an oral medication indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with a left ventricular ejection fraction (LVEF) of 35% or less, who are in sinus rhythm with a resting heart rate of 70 beats per minute (bpm) or more, and who are receiving maximally tolerated doses of beta blockers or have a contraindication to beta blocker use.
Heart failure affects approximately 5.7 million people in the U.S., about half of whom have reduced left ventricular function. Despite the broad use of standard treatments, the prognosis for patients with heart failure is poor. Projections show that by 2030, the prevalence of heart failure will increase 46% from 2012 estimates.
Heart failure costs an estimated $31 billion in the U.S. each year, with most of the cost related to hospitalizations. By 2030, the cost of heart failure in the U.S. is expected to increase by almost 127%, totaling $70 billion.
“The approval of Corlanor is an important step forward for the treatment of patients with chronic heart failure in the U.S. Because its mechanism of action is unique, it will complement the use of standard heart failure therapies, including beta blockers,” said Jeffrey S. Borer, MD, of the State University of New York, Downstate Medical Center. “Despite beta blockade and other therapies, many people with chronic heart failure continue to suffer hospitalizations due to worsening heart failure. For these patients, when heart rate is greater than or equal to 70 bpm, Corlanor may be an appropriate treatment option and can be expected to add benefit.”
Ivabradine blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker, which regulates heart rate. The drug reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If current (the “funny” current) to slow the heart rate with no effects on ventricular repolarization or myocardial contractility.
The FDA’s approval of ivabradine was based on global clinical trial data, including the findings of a large, randomized, double-blind, placebo-controlled outcomes trial. The phase III Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT) compared ivabradine with placebo on top of standard of care (SOC) therapies, including beta blockers, in more than 6,500 clinically stable patients in sinus rhythm with a reduced LVEF (35% or less) and a resting heart rate of 70 bpm or more, with a hospitalization for heart failure within the past 12 months. Patients received SOC, including beta blockers (89%), angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARBs) (91%), diuretics (83%), and anti-aldosterone agents (60%).
Ivabradine significantly reduced the risk of the primary composite endpoint of hospitalization or cardiovascular death for worsening heart failure, with an 18% relative risk reduction (RRR) compared with placebo (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. Treatment resulted in a 26% RRR in the risk of hospitalizations for worsening heart failure.
The most common adverse events in patients treated with ivabradine compared with those given placebo included bradycardia (10.0% vs. 2.2%, respectively), hypertension or increased blood pressure (8.9% vs. 7.8%), atrial fibrillation (8.3% vs. 6.6%), and luminous phenomena (phosphenes) or visual brightness (2.8% vs. 0.5%).
The recommended starting dosage of ivabradine is a 5-mg tablet administered twice daily with meals. After 2 weeks of treatment, the dose should be assessed and adjusted depending on the patient’s heart rate. In patients with a history of conduction defects, or in other patients in whom bradycardia could lead to hemodynamic compromise, therapy should be initiated at 2.5 mg twice daily before increasing the dose based on the heart rate.
Ivabradine is expected to be available to patients in approximately 1 week.
Source: Amgen; April 16, 2015.