Trend of Clinical Outcome and Surrogate Markers During Titration of β-Blocker in Heart Failure Patients With Reduced Ejection Fraction

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure with reduced ejection fraction (HFrEF) (n=227). Intervention: Beta-blocker dose fixation after January 1, 2006 (recent era up-titration policy) vs. Beta-blocker dose fixation before December 31, 2005 (remote era). Primary outcome: Composite of hospitalization for worsening heart failure and/or all-cause death (HR 0.90, 95% CI 0.83-0.98, p=0.012).

Naoko Kato; Koichiro Kinugawa; Teruhiko Imamura; Hironori Muraoka; Shun Minatsuki; Toshiro Inaba; Hisataka Maki; Taro Shiga; Masaru Hatano; Atsushi Yao; Issei Komuro; Ryozo Nagai

doi:10.1253/circj.cj-12-1241

December 18, 2012Circulation JournalOpen Access

Trend of Clinical Outcome and Surrogate Markers During Titration of β-Blocker in Heart Failure Patients With Reduced Ejection Fraction

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Key result

Beta-blocker dose fixation in the recent era (after January 2006) reduced the risk of heart failure hospitalization or all-cause death by 10% compared to the remote era in patients with HFrEF.

Why the study?

Does a more aggressive beta-blocker up-titration policy improve the composite of heart failure hospitalization or all-cause death in patients with HFrEF?

Study Design

Type

Cohort (n=227)

Multicenter

No

Structured PICO

Does a more aggressive beta-blocker up-titration policy improve the composite of heart failure hospitalization or all-cause death in patients with HFrEF?

P

Population

227 patients with heart failure with reduced ejection fraction (LVEF <50%) starting de novo beta-blocker therapy, followed for a median of 36 months.

E

Exposure

Beta-blocker up-titration policy in the recent era (after Jan 1, 2006), achieving higher fixed doses (mean 9.5 mg/day carvedilol equivalent) and lower resting heart rate (mean 70.2 beats/min).

C

Comparator

Beta-blocker titration in the remote era (before Dec 31, 2005), achieving lower fixed doses (mean 6.2 mg/day carvedilol equivalent) and higher resting heart rate (mean 74.2 beats/min).

O

Outcome

Composite endpoint of hospitalization for worsening heart failure and/or all-cause death at median 36 months follow-up.composite

Main Result

Hazard Ratio: 0.9 (95% CI 0.83–0.98)

Absolute Event Rate: 22% vs 38%

p-value: p=0.012

Limitations

Conducted in a single center and data were analyzed in a retrospective fashion
Not a randomized trial and used a historical control
Included patients with atrial fibrillation, where the association between heart rate and clinical events may differ
Doses of ACEI or ARB were not titrated once introduced and remained less than half the target dose
Single center and retrospective analysis
Included patients with atrial fibrillation where heart rate may not predict events
Doses of ACEI or ARB were not titrated once introduced

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Implication

Higher beta-blocker doses (≥10 mg/day carvedilol equivalent) and lower achieved resting heart rates (≤71 beats/min) are associated with significantly improved clinical outcomes in Japanese patients with HFrEF.

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%). METHODS AND 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.

Discussion

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Cite This Study

Kato et al. (2012) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=227). Beta-blocker dose fixation after January 1, 2006 (recent era up-titration policy) vs. Beta-blocker dose fixation before December 31, 2005 (remote era) was evaluated on Composite of hospitalization for worsening heart failure and/or all-cause death (HR 0.90, 95% CI 0.83-0.98, p=0.012). Beta-blocker dose fixation in the recent era (after January 2006) reduced the risk of heart failure hospitalization or all-cause death by 10% compared to the remote era in patients with HFrEF.

synapsesocial.com/papers/6a95ac881c752b9006a8e6c0 https://doi.org/10.1253/circj.cj-12-1241

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Trend of Clinical Outcome and Surrogate Markers During Titration of β-Blocker in Heart Failure Patients With Reduced Ejection Fraction

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Trend of Clinical Outcome and Surrogate Markers During Titration of β-Blocker in Heart Failure Patients With Reduced Ejection Fraction

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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