Anemia Is Associated With Blunted Response to β-Blocker Therapy Using Carvedilol ― Insights From Japanese Chronic Heart Failure (J-CHF) Study ―

Yuji Nagatomo, Tsutomu Yoshikawa, Hiroshi Okamoto, Akira Kitabatake, Masatsugu Hori, on behalf of J-CHF Investigators

Anemia portends a poor clinical outcome in patients with chronic heart failure (CHF). However, its mechanism remains unknown. We sought to elucidate the effect of anemia on patients with HF with reduced ejection fraction (HFrEF) who receive carvedilol therapy.Methods and Results:J-CHF study was a prospective, randomized, multicenter trial that assigned 360 HFrEF patients to 2.5 mg/5 mg/20 mg carvedilol groups according to the target dose. At baseline 70 patients (19%) had anemia ([A]) defined as hemoglobin level (Hb) <13 g/dL (male) or <12 g/dL (female) and the remaining 290 did not ([N]). Allocated and achieved doses of carvedilol were similar. Left ventricular ejection fraction (LVEF) and plasma B-type natriuretic peptide (BNP) level significantly improved in both groups over 56 weeks, but they were smaller in [A] than in [N] (LVEF, P=0.046; BNP, P<0.0001 by ANOVA). Baseline Hb was an independent predictor of absolute change in LVEF (β=0.13, P=0.047) and BNP (β=-0.10, P=0.01). Presence of chronic kidney disease defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2)at baseline was not associated with differential response to carvedilol therapy. During 3.8±1.4 years follow-up, group [A] had a higher incidence of the composite endpoint of death, hospitalization for cardiovascular causes including HF compared with [N] (P=0.006). Baseline Hb was an independent predictor of the composite endpoint (hazard ratio 0.86, P=0.04), whereas baseline eGFR was not. Our data suggested that anemia was associated with a blunted response to carvedilol in HFrEF patients.