title: Emerging role of ivabradine for rate control in atrial fibrillation.
abstract: Control of ventricular rate is recommended for patients with paroxysmal, persistent, or permanent atrial fibrillation (AF). Existing rate-control options, including beta-blockers, nondihydropyridine calcium channel blockers, and digoxin, are limited by adverse hemodynamic effects and their ability to attain target heart rate (HR). Ivabradine, a novel HR-controlling agent, decreases HR through deceleration of conduction through If('funny') channels, and is approved for HR reduction in heart failure patients with ejection fraction less than 35% and elevated HR, despite optimal pharmacological treatment. Because Ifchannels were thought to be expressed solely in sinoatrial (SA) nodal tissue, ivabradine was not investigated in heart failure patients with concomitant AF. Subsequent identification of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4), the primary gene responsible for Ifcurrent expression throughout the myocardium, stimulated interest in the potential role of ivabradine for ventricular rate control in AF. Preclinical studies of ivabradine in animal models with induced AF demonstrated a reduction in HR, with no significant worsening of QT interval or mean arterial pressure. Preliminary human data suggest that ivabradine provides HR reduction without associated hemodynamic complications in patients with AF. Questions remain regarding efficacy, safety, optimal dosing, and length of therapy in these patients. Prospective, randomized studies are needed to determine if ivabradine has a role as a rate-control treatment in patients with AF.
authors.affiliation: PGY2 Internal Medicine Pharmacy Resident, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond, VA, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Turley
authors.affiliation: Department of Pharmacy Services, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, and Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Francis
authors.affiliation: Department of Pharmacy Services, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, and Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.
authors.forename: Denise K
authors.initials: DK
authors.lastname: Lowe
authors.affiliation: Department of Pharmacy Services, Virginia Commonwealth University School of Pharmacy, 401 North 12th Street, P.O. Box 980042, Richmond, VA 23298-0042, USA william.cahoon@vcuhealth.org.
authors.forename: William D
authors.initials: WD
authors.lastname: Cahoon
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D001552:Benzazepines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged
chemical_list: D001552:Benzazepines; D054815:Cyclic Nucleotide-Gated Cation Channels; D000077550:Ivabradine
keywords: atrial fibrillation; funny channel; heart rate; ivabradine; rate control