Trend of clinical outcome and surrogate markers during titration of ß-blocker in heart failure patients with reduced ejection fraction: relevance of achieved heart rate and ß-blocker dose.

ABSTRACT

BACKGROUND: The aim of this study was to examine trends of clinical outcome and to clarify surrogate markers when titrating ß-blocker in heart failure patients with reduced left ventricular ejection fraction (HFrEF, LVEF <50%). METHODS AND RESULTS: Consecutive HFrEF patients starting on ß-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 ß-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 ß-blocker ≥10mg/day (ie, 50% of the target dose for Japanese patients) could be surrogate markers when titrating ß-blocker.