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FDA Approves Corlanor® (ivabradine) To Reduce The Risk Of Hospitalization For Worsening Heart Failure In Patients With Chronic Heart Failure
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Heart failure is a common condition that affects approximately 5.7 million people in the U.S., about half of which have reduced left ventricular function.1,2 Despite broad use of standard treatments, the prognosis for patients with heart failure is poor.3 Projections show that by 2030, the prevalence of heart failure will increase 46 percent from 2012 estimates.1
"We are excited to introduce Corlanor, the first new chronic heart failure medicine approved by the
Heart failure costs an estimated
"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
Corlanor blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker, which regulates heart rate. Corlanor reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If current ("funny" current) to slow the heart rate with no effect on ventricular repolarization and no effects on myocardial contractility.5
The Corlanor approval is based on global clinical trial data including a large, multicenter, randomized, double-blind, placebo-controlled, outcomes trial. The Phase 3 SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) study compared Corlanor to placebo on top of standard of care (SOC) therapies, including beta blockers, in more than 6,500 clinically stable (≥4 weeks) patients in sinus rhythm with reduced left ventricular function (LVEF ≤35 percent) and heart rate ≥70 bpm, with a hospitalization for heart failure within the past 12 months. Patients received SOC, including beta blockers (89 percent), angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARB) (91 percent), diuretics (83 percent) and anti-aldosterone agents (60 percent).
Results from the Phase 3 SHIFT study showed Corlanor significantly reduced the risk of the primary composite endpoint of hospitalization or cardiovascular death for worsening heart failure, with 18 percent relative risk reduction (RRR) (p<0.0001, 4.2 percent absolute risk reduction [ARR]) versus placebo. 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. There was a 26 percent RRR (4.7 percent ARR) in the risk of hospitalizations for worsening heart failure.
The most common adverse drug reactions in the SHIFT study occurring in ≥1 percent of patients on Corlanor compared to placebo were bradycardia (10 percent vs. 2.2 percent), hypertension or increased blood pressure (8.9 percent vs. 7.8 percent), atrial fibrillation (8.3 percent vs. 6.6 percent), and luminous phenomena (phosphenes) or visual brightness (2.8 percent vs. 0.5 percent).
The recommended starting dose of Corlanor is a 5 mg tablet twice daily with meals. After two weeks of treatment, the dose should be assessed and adjusted depending on heart rate. In patients with a history of conduction defects, or other patients in whom bradycardia could lead to hemodynamic compromise, initiate therapy at 2.5 mg twice daily before increasing the dose based on heart rate.
Corlanor is expected to be available to patients in approximately one week.
About Corlanor® (ivabradine)
Corlanor blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker, which regulates heart rate. Corlanor reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If current ("funny" current) to slow the heart rate with no effect on ventricular repolarization and no effects on myocardial contractility.5 Corlanor was developed by Les Laboratoires Servier. Through a collaboration with Servier,
Important U.S. Product Information
Corlanor® is 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 (bpm) and either are on maximally tolerated doses of beta blockers or have a contraindication to beta blocker use.
Important Safety Information
- Contraindications: Corlanor® is contraindicated in patients with acute decompensated heart failure, blood pressure < 90/50 mmHg, sick sinus syndrome, sinoatrial block, 3rd degree AV block (unless a functioning demand pacemaker is present), a resting heart rate < 60 bpm prior to treatment, severe hepatic impairment, pacemaker dependence (heart rate imposed exclusively by the pacemaker) and concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors.
- Fetal Toxicity: Corlanor® may cause fetal toxicity when administered to a pregnant woman.
- Atrial Fibrillation: Corlanor® increases the risk of atrial fibrillation. The rate of atrial fibrillation in patients treated with Corlanor® compared to placebo was 5% vs. 3.9% per patient-year, respectively.
- Bradycardia and Conduction Disturbances: Bradycardia, sinus arrest and heart block have occurred with Corlanor®. Concurrent use of verapamil or diltiazem also increases Corlanor® exposure and should be avoided. Avoid use of Corlanor® in patients with 2nd degree atrioventricular block unless a functioning demand pacemaker is present.
- Adverse Reactions: The most common adverse drug reactions in the SHIFT study occurring in ≥ 1% higher on Corlanor® than placebo were bradycardia (10% vs. 2.2%), 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%).
Please contact Amgen Medinfo at 800-77-
About Amgen Cardiovascular
Building on more than three decades of experience in developing biotechnology medicines for patients with serious illnesses,
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- Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics – 2015 update: a report from the
American Heart Association. Circulation. 2015;131:e29-e332.
- Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart failure: A Report of the
American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240-e327.
- Swedberg K, Komajda M, Bohm M, et al. Ivabradine and Outcomes in Chronic Heart failure (SHIFT): a Randomised Placebo Controlled Study. Lancet. 2010; 376:875-85.
- Heidenriech PA, Albert NM,
Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6:606-619.
- Corlanor® U.S. Prescribing Information.
World Health Organization. Cardiovascular diseases (CVDs) fact sheet. http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed April 2015.
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