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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
University of Tokyo, Japan .
University of Tokyo, Japan .
University of Tokyo, Japan .
University of Tokyo, Japan .
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2013 (English)In: Circulation Journal, ISSN 1346-9843, E-ISSN 1347-4820, Vol. 77, no 4, 1001-1008 p.Article in journal (Refereed) Published
Abstract [en]


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%).


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).


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.

Place, publisher, year, edition, pages
Japanese Circulation Society , 2013. Vol. 77, no 4, 1001-1008 p.
Keyword [en]
Beta-blocker; Heart failure; Heart rate; Morbidity; Mortality
National Category
Health Sciences
URN: urn:nbn:se:liu:diva-111185DOI: 10.1253/circj.CJ-12-1241ISI: 000318203200027PubMedID: 23258250OAI: diva2:754520

Funding Agencies|Japan Society for the Promotion of Science [224943]; Japanese Heart Foundation; Japanese Association for Cerebro-Cardiovascular Disease Control; AstraZeneca; Pfizer Health Research Foundation; FUGAKU Trust for Medical Research; Japan Society for the Promotion of Science (JSPS)

Available from: 2014-10-10 Created: 2014-10-10 Last updated: 2014-10-20Bibliographically approved

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Kato, Naoko
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