"Darbepoetin Alfa in Systolic Heart Failure and Anemia".The New England Journal of Medicine. 2013.
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Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcomes
9 Funding
10 Further Reading

Clinical Question

Does the use of darbepoetin alfa improve clinical outcomes in patients with systolic heart failure and anemia?

Bottom Line

Darbepoetin alfa, targeted to increase hemoglobin, did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia and was associated with increased thromboembolic events.

Major Points

Anemia is common in heart failure patients and associated with worse symptoms, functional capacity, and outcomes. Despite increasing hemoglobin levels, treatment with darbepoetin alfa in this patient population did not reduce the risk of the primary outcome of death or hospitalization for worsening heart failure and increased the risk of thromboembolic events.

Guidelines

Current guidelines do not support the use of erythropoiesis-stimulating agents like darbepoetin alfa for anemia in patients with systolic heart failure.

Design

- Randomized, double-blind, placebo-controlled trial
- N=2,278 patients with systolic heart failure and mild-to-moderate anemia
- Darbepoetin alfa group (n=1,136) vs. placebo group (n=1,142)
- Setting: 453 sites in 33 countries
- Enrollment: June 13, 2006, to May 4, 2012
- Median follow-up: 28 months
- Analysis: Intention-to-treat
- Primary outcome: Composite of death from any cause or hospitalization for worsening heart failure

Population

Inclusion Criteria
- NYHA functional class II, III, or IV heart failure
- Left ventricular ejection fraction of ≤40%
- Mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter)
- Receiving guideline-recommended heart failure therapy

Exclusion Criteria
- Transferrin saturation <15%
- Signs of bleeding or correctable causes of anemia
- Serum creatinine >3 mg per deciliter
- Uncontrolled hypertension (>160/100 mm Hg)

Baseline Characteristics
- Median age: 72.0 years
- 41% female
- 65% had NYHA class III or IV disease
- Median left ventricular ejection fraction: 31%
- Median estimated GFR: 45.7 ml/min/1.73 m^2

Interventions

- Patients were randomly assigned to darbepoetin alfa or placebo
- Darbepoetin alfa: starting dose of 0.75 μg/kg every 2 weeks until hemoglobin level of 13.0 g/dL achieved, then monthly adjustments
- Placebo: mimicked dosage adjustments of darbepoetin alfa group
- Oral and intravenous iron supplementation according to protocol as needed

Outcomes

Primary Outcomes
- Death from any cause or hospitalization for worsening heart failure:
- 50.7% in the darbepoetin alfa group
- 49.5% in the placebo group
- Hazard ratio in the darbepoetin alfa group: 1.01; 95% CI, 0.90 to 1.13; P=0.87

Secondary Outcomes
- Death from cardiovascular causes or hospitalization for worsening heart failure similar in both groups
- Improvements in KCCQ Overall Summary and Symptom Frequency Scores higher in the darbepoetin alfa group but of questionable clinical importance
- Fatal or nonfatal stroke:
- 3.7% in darbepoetin alfa group
- 2.7% in placebo group; P=0.23
- Thromboembolic events:
- 13.5% in darbepoetin alfa group
- 10.0% in placebo group; P=0.01

Funding

Supported by Amgen.

Further Reading

The accompanying article and additional study material can be found on the New England Journal of Medicine website.