title: Trend of clinical outcome and surrogate markers during titration of β-blocker in heart failure patients with reduced ejection fraction: relevance of achieved heart rate and β-blocker dose.
abstract: BACKGROUND
  The aim of this study was to examine trends of clinical outcome and to clarify surrogate markers when titrating β-blocker in heart failure patients with reduced left ventricular ejection fraction (HFrEF, LVEF <50%).
  
  
  RESULTS
  Consecutive HFrEF patients starting on β-blocker were divided into 2 groups according to time of dose fixation attainment: before 31 December 2005 (group 1, n=108) or after 1 January 2006 (group 2, n=119). There were no significant differences in patient characteristics between the 2 groups at baseline. Beta-blocker fixed dose was higher with lower resting heart rate in group 2 (6.2±5.7mg/day vs. 9.5±9.1mg/day in carvedilol equivalent dose, P=0.001; 74.2±11.1beats/min vs. 70.2±9.7beats/min, P=0.004). The rate of HF hospitalization and/or all-cause death after 36 months was lower in group 2 than in group 1 (22% vs. 38%, P=0.011; hazard ratio, 0.90; P=0.012). Cox regression analysis showed that β-blocker ≥10mg/day and achieved heart rate ≤71beats/min predicted a better outcome (both P<0.05).
  
  
  CONCLUSIONS
  Recent improvement of clinical outcome among HFrEF patients may be attributable to the up-titration policy accompanying lowered heart rate. Resting heart rate ≤71beats/min and β-blocker ≥10mg/day (ie, 50% of the target dose for Japanese patients) could be surrogate markers when titrating β-blocker.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kato
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kinugawa
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Imamura
authors.forename: Hironori
authors.initials: H
authors.lastname: Muraoka
authors.forename: Shun
authors.initials: S
authors.lastname: Minatsuki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Inaba
authors.forename: Hisataka
authors.initials: H
authors.lastname: Maki
authors.forename: Taro
authors.initials: T
authors.lastname: Shiga
authors.forename: Masaru
authors.initials: M
authors.lastname: Hatano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yao
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000368:Aged; D015415:Biomarkers; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D015415:Biomarkers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol