The medical letter on drugs and therapeutics may 25 2015

The Medical Letter ® on Drugs and Therapeutics Objective Drug Reviews Since 1959 Volume 57 ISSUE ISSUE No 1433 1469 Volume 56 May 25, 2015 IN THIS ISSUE Ivabradine (Corlanor) for Heart Failure p 75 Fluticasone Furoate (Arnuity Ellipta) for Asthma p 76 Ceftazidime/Avibactam (Avycaz) — A New Intravenous Antibiotic p 79 New Website and App Announcement p 80 Important Copyright Message FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter, Inc publications are protected by U.S and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with U.S and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 The Medical Letter ® on Drugs and Therapeutics Objective Drug Reviews Since 1959 Volume 57 ISSUE ISSUE No 1433 1469 Volume 56 ▶ May 25, 2015 Take CME Exams ALSO IN THIS ISSUE Fluticasone Furoate (Arnuity Ellipta) for Asthma p 76 Ceftazidime/Avibactam (Avycaz) — A New Intravenous Antibiotic p 79 New Website and App Announcement p 80 Ivabradine (Corlanor) for Heart Failure The FDA has approved ivabradine (Corlanor – Amgen) to reduce the risk of hospitalization for worsening heart failure in adults with stable, symptomatic chronic heart failure with left ventricular ejection fraction (LVEF) ≤35% who are in sinus rhythm with a resting heart rate ≥70 beats per minute and who are on maximum tolerated doses of beta blockers or have a contraindication to beta blocker use Ivabradine has been available internationally for years as Procoralan and Corlentor for treatment of stable angina and heart failure Pronunciation Key Ivabradine: eye vab’ deen Corlanor: kor’ lan or STANDARD TREATMENT — All patients with heart failure with reduced ejection fraction (LVEF ≤40%) generally should take both an angiotensin-converting enzyme (ACE) inhibitor and a beta blocker, and if volume overloaded, a diuretic as well An angiotensin receptor blocker (ARB) is recommended for patients who cannot tolerate an ACE inhibitor In patients with symptomatic heart failure and ejection fraction ≤35%, or reduced ejection fraction after a myocardial infarction, addition of an aldosterone antagonist can reduce the risk of hospitalization or death Addition of hydralazine/ isosorbide dinitrate (BiDil) to standard therapy has been shown to reduce symptoms and mortality in black patients with NYHA class III-IV heart failure with reduced ejection fraction Digoxin can decrease symptoms and lower the rate of hospitalization for heart failure, but it does not reduce mortality.1 MECHANISM OF ACTION — Ivabradine slows heart rate by inhibiting the cardiac pacemaker If current It has no effect on ventricular repolarization or myocardial contractility Table Pharmacology Class Hyperpolarization-activated cyclic nucleotidegated channel blocker Formulation Route Tmax Metabolism Elimination 5-, 7.5-mg tablets (5-mg tabs are scored) Oral ~1 hr Primarily hepatic via CYP3A4 Urine (~4% unchanged); metabolites in feces and urine ~6 hours Half-life CLINICAL STUDIES — Approval of Corlanor was based on a randomized, double-blind, placebo-controlled trial (SHIFT) in 6558 adults with NYHA class II-IV heart failure, LVEF ≤35%, and a resting heart rate ≥70 bpm who had been hospitalized for heart failure within 12 months before study entry In addition to their background treatment, which generally included a beta blocker, patients received either ivabradine mg twice daily, which could be increased to 7.5 mg twice daily or decreased to 2.5 mg twice daily to maintain a resting heart rate between 50 and 60 bpm, or placebo After a median follow-up of 22.9 months, a composite of hospitalization for worsening heart failure or cardiovascular death, the primary endpoint, occurred in significantly fewer patients taking ivabradine than taking placebo (24% vs 29%) Ivabradine significantly reduced the risk of hospitalization for worsening heart failure (16% vs 21% with placebo) and death due to heart failure (3% vs 5%), but it did not have a significant effect on cardiovascular death (14% vs 15%).2 In a trial in 10,917 patients with coronary artery disease and stable heart failure (BEAUTIFUL), ivabradine did not significantly affect the primary composite endpoint of cardiovascular death, hospitalization for acute MI, or hospitalization for new-onset or worsening heart failure, compared to placebo.3 75 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter ® In another placebo-controlled trial in 19,102 patients who had coronary artery disease without clinically evident heart failure (SIGNIFY), ivabradine also did not significantly affect the primary endpoint, a composite of cardiovascular death or nonfatal MI Moreover, a prespecified subgroup analysis in patients with more than minimal angina pectoris found a significantly higher incidence of the primary endpoint with ivabradine (7.6% vs 6.5% with placebo).4 ADVERSE EFFECTS — The most common adverse effects of ivabradine in the SHIFT trial were bradycardia, hypertension, atrial fibrillation, and visual disturbances (transient increases in brightness) caused by inhibition of electric currents in the retina These disturbances, called phosphenes, generally occurred within the first months of ivabradine treatment; most were of mild to moderate intensity and resolved during or after treatment Syncope, hypotension, angioedema, erythema, rash, pruritus, urticaria, vertigo, diplopia, and visual impairment have also been reported Table Contraindications to Ivabradine ▶ ▶ ▶ ▶ ▶ ▶ ▶ Acute decompensated heart failure Blood pressure