title: Heart rate control by carvedilol in Japanese patients with chronic atrial fibrillation: The AF Carvedilol study.
abstract: β-Blockers are used to control heart rate (HR) in patients with atrial fibrillation (AF). However, the appropriate dosage and efficacy of carvedilol in Japanese AF patients are yet to be clarified.
  
  
  
  In this multicenter, randomized, double-blind study, Japanese patients with persistent or permanent AF received carvedilol for 6 weeks in the following three dosage-regimen groups: 5-mg fixed-dose (n=42), 10-mg dose-escalation (n=42), or 20-mg dose-escalation (n=43). To evaluate the efficacy of each dosage regimen and the dose-response relationship, changes in 24-h mean HR (mHR) on Holter electrocardiograms from baseline to weeks 2, 4, and 6 were determined as primary endpoints. The effects on circadian changes in HR, the proportion of patients achieving target HR, clinical symptoms, and adverse events were also examined.
  
  
  
  After 2 weeks, carvedilol 5mg decreased 24-h mHR significantly [6.6 (95% CI: 5.2-8.0)beats/min, p<0.0001]. After 6 weeks, carvedilol showed a trend of dose-dependent HR reduction (p=0.0638): 7.6 (5.4-9.8) in the 5-mg fixed-dose group; 8.9 (6.7-11.1) in the 10-mg dose-escalation group; and 10.6 (8.4-12.8)beats/min in the 20-mg dose-escalation group. There were no serious adverse events related to carvedilol.
  
  
  
  In Japanese patients with persistent or permanent AF, carvedilol at 5mg once daily demonstrated a significant HR reduction, and step-wise dose escalation from 5mg to 20mg showed a trend of dose-dependent HR reduction.
authors.affiliation: Saiseikai Toyama Hospital, Toyama, Japan. Electronic address: h-inoue@saiseikai-toyama.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Internal Medicine, Nippon Medical School Tama-Nagayama Hospital, Tokyo, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Atarashi
authors.affiliation: Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine, Aomori, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Clinical Execution Department, Daiichi Sankyo Co Ltd, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fukuzawa
authors.affiliation: Clinical Data & Biostatistics Department, Daiichi Sankyo Co Ltd, Tokyo, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Shiosakai
authors.affiliation: Clinical Planning Department, Daiichi Sankyo Co Ltd, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage*
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
keywords: Atrial fibrillation; Carvedilol; Heart rate control