The heart rate–lowering agent ivabradine was approved by the Food and Drug Administration on April 15 to reduce hospitalizations in patients with worsening heart failure.
In an April 15 statement, the FDA announced that ivabradine, after undergoing a fast-track evaluation process, is indicated in patients with chronic, stable, symptomatic heart failure and left ventricular ejection fractions at or below 35%; resting heart rates of at least 70 beats per minute; and who are on maximum beta-blockers doses or have beta-blocker contraindications.
Ivabradine “is thought to work by decreasing heart rate and represents the first approved product in [its] drug class,” Dr. Norman Stockbridge, director of the FDA’s division of cardiovascular and renal products, said in a written statement.
The drug was given priority review based on the results of SHIFT (Systolic Heart Failure Treatment With the I f Inhibitor Ivabradine Trial), which involved 6,505 clinically stable patients, all hospitalized for heart failure in the preceding year and all on standard background therapy, including beta-blockers (89%), ACE inhibitors and/or angiotensin II receptor blockers (91%), diuretics (83%), and antialdosterone agents (60%) (Lancet 2010;376:875-85).
There was a 4.7% absolute risk reduction and a 26% relative risk reduction for hospitalizations as a result of deteriorating heart failure in the 3,241 ivabradine patients, but the drug did not reduce mortality, according to a statement from the drug’s manufacturer, Amgen.
The most common adverse events were bradycardia (10% vs. 2.2% with placebo), hypertension or increased blood pressure (8.9% vs. 7.8% with placebo), atrial fibrillation (8.3% vs. 6.6%), and luminous phenomena or visual brightness (2.8% vs. 0.5%).
Ivabradine is a specific inhibitor of the I f (“funny”) current in the sinoatrial node, but not other currents. The drug is contraindicated in patients with acute decompensated heart failure, blood pressure below 90/50 mm Hg, sick sinus syndrome, sinoatrial block, third-degree AV block (unless a functioning demand pacemaker is present), resting heart rate below 60 bpm prior to treatment, severe hepatic impairment, pacemaker dependence, and use of strong cytochrome P450 3A4 inhibitors. Ivabradine increases the risk of atrial fibrillation and can cause fetal toxicity. Bradycardia, sinus arrest, and heart block have been reported with its use, Amgen said in its announcement.
Concurrent use of the calcium channel blockers verapamil or diltiazem increases exposure to the drug and should be avoided. Ivabradine also should be avoided in patients with second-degree AV block unless a functioning demand pacemaker is present.
Ivabradine will be available in 5-mg and 7.5-mg tablets, according to the product’s label. The recommended starting dose is a 5-mg tablet twice daily with meals. After 2 weeks of treatment, the dose should be adjusted depending on heart rate. In patients with a history of conduction defects or others in whom bradycardia could lead to hemodynamic compromise, Amgen said to initiate therapy at 2.5 mg twice daily.
Patients should alert their health care professional if they develop an irregular heartbeat, a pounding or racing heart, chest pressure, worse shortness of breath, dizziness, weakness, or fatigue, Amgen said.
Ivabradine will be available within about a week of the approval under the trade name Corlanor, and will come with a patient medication guide. Wholesale acquisition cost will be $4,500 per year, or $375 per month, and patient costs will vary according to insurance coverage, said Amgen spokesman Cuyler Mayer.
Ivabradine has been available in Europe as Procoralan for several years.
