Darbepoetin did not improve clinical outcomes for systolic heart failure, anemia

Darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild to moderate anemia, a study found.

Researchers conducted a double-blind trial that randomly assigned 2,278 patients with systolic heart failure and mild to moderate anemia (hemoglobin level, 9.0 to 12.0 g/dL) to receive either darbepoetin to a hemoglobin target of 13 g/dL or placebo. Primary clinical outcomes were death from any cause or first hospitalization for worsening heart failure. Secondary outcomes included the Summary Score and Symptom Frequency Score on the Kansas City Cardiomyopathy Questionnaire. These scores are based on a 100-point scale with higher scores indicating a better quality of life and fewer symptoms; a change of 5 points is considered clinically meaningful. The study was published early online March 10 by New England Journal of Medicine.

The primary composite outcome of death from any cause or first hospitalization for worsening heart failure occurred in 576 patients (50.7%) in the darbepoetin group and 565 (49.5%) in the placebo group (hazard ratio [HR] in the darbepoetin group, 1.01; 95% CI, 0.90 to 1.13; P=0.87). Results were similar when adjusted for baseline characteristics (adjusted HR, 1.01; 95% CI, 0.90 to 1.13; P=0.88), in the as-treated analysis (HR, 0.98; 95% CI, 0.86 to 1.13; P=0.82) and across all subgroups examined.

There were 474 deaths (41.7%) in the darbepoetin group and 458 (40.1%) in the placebo group (HR, 1.04; 95% CI, 0.92 to 1.19; P=0.51), for annualized mortality rates of 14.4% and 13.8%, respectively. There were similar rates of death from cardiovascular causes, of first hospitalization for worsening heart failure, and on each component of the composite outcome. Five hundred seventy-two hospitalizations for heart failure (including second and subsequent hospitalizations) occurred in the darbepoetin group and 695 occurred in the placebo group (P=0.06 from a negative binomial model).

An improvement in the Overall Summary Score on the Kansas City Cardiomyopathy Questionnaire of 5 points or more at six months was seen in 53% of the darbepoetin group and 48% of the placebo group (P=0.06). Increases from baseline to six months in the Symptom Frequency Score were 6.20 points (95% CI, 4.71 to 7.69 points) in the darbepoetin group and 3.91 points (95% CI, 2.42 to 5.40 points) in the placebo group (P=0.01).

There were similar adverse event rates for the drug compared to placebo. Embolic and thrombotic adverse events were reported in 153 patients (13.5%) in the darbepoetin group and 114 (10.0%) in the placebo group (P=0.01). Septic shock was reported significantly more frequently in the darbepoetin group than in the placebo group, although there was no excess of other serious adverse events related to infection in the darbepoetin group. Stroke and cancer rates did not significantly differ between treatment and control groups, and there was no significant between-group difference in systolic blood pressure during the study.

The researchers wrote, “[O]ur findings suggest that the hemoglobin level, like other surrogates, is simply a marker of poor prognosis in heart failure rather than a therapeutic target.”