Erythropoietin as a Treatment of Anemia in Heart Failure
Erythropoietin as a Treatment of Anemia in Heart Failure
Background Anemia in heart failure is both common and associated with worse symptoms and increased mortality. Several small randomized controlled trials (RCTs) have assessed erythropoiesis-stimulating agents (ESAs), but definitive evaluation and clinical guidance are required. We sought to systematically review the effects of ESAs in chronic heart failure.
Methods An extensive search strategy identified 11 RCTs with 794 participants comparing any ESA with control over 2 to 12 months of follow-up. Published and additionally requested data were incorporated into a Cochrane systematic review (CD007613).
Results Nine studies were placebo controlled, and 5, double blinded. Erythropoiesis-stimulating agent treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2–188.4, P = .04) and 6-minute walk distance by 69.3 m (95% CI 17.0–121.7, P = .009) compared with control. Benefit was also noted for peak oxygen consumption (+2.29 mL/kg per minute, P = .007), New York Heart Association class (−0.73, P < .001), ejection fraction (+5.8%, P < .001), B-type natriuretic peptide (−226.99 pg/mL, P < .001), and quality-of-life indicators with a mean increase in hemoglobin level of 2 g/dL. There was a significantly lower rate of heart failure–related hospitalizations with ESA therapy (odds ratio 0.56, 95% CI 0.37–0.84, P = .005). No associated increase in adverse events or mortality (odds ratio 0.58, 95% CI 0.34–0.99, P = .047) was observed, although the number of events was limited.
Conclusion Meta-analysis of small RCTs suggests that ESA treatment can improve exercise tolerance, reduce symptoms, and have benefits on clinical outcomes in anemic patients with heart failure. Confirmation requires larger, well-designed studies with careful attention to dose, attained hemoglobin level, and long-term outcomes.
Anemia in patients with chronic heart failure (CHF) is common, occurring in up to half of all patients depending on the population studied and the definition applied. Meta-analysis of >150,000 patients with CHF has identified that low hemoglobin level nearly doubles the risk of all-cause mortality over a 6-month to 5-year follow-up period, irrespective of whether CHF is due to systolic or diastolic dysfunction. Thus, anemia in CHF presents a therapeutic target with the potential for considerable improvement in clinical outcomes.
Erythropoiesis-stimulating agents (ESAs) are an established treatment of anemia in chronic kidney disease and cancer, although recent concerns have been raised over safety, particularly when titrated to a high hemoglobin level. However, the benefit of ESAs on quality of life in chronically ill patients is well documented. Erythropoietin as a treatment of anemia in patients with CHF has been studied in several small randomized controlled trials (RCTs) using a variety of preparations and doses. An overall benefit for reduced hospitalization has been noted, but the mechanism for this improvement is still unclear. There are also conflicting data on the effects of ESAs on exercise capacity, functional status, and mortality in patients with CHF, all of which are key issues in determining the cost-effectiveness of routine clinical administration of erythropoietin.
We sought to clarify these issues and determine the overall benefit and potential harm of ESA therapy in anemic patients with CHF using available RCTs. A range of outcomes were examined to fully understand the effects and mechanism of action. These included subjective and objective assessments of symptoms (quality-of-life measures and New York Heart Association [NYHA] classification) as well as functional and numerical evaluation of left ventricular exercise capacity and ejection fraction. We also reviewed CHF-related hospital admissions, all-cause mortality, and major adverse effects of erythropoietin treatment, updating postpublication outcomes where data were available. Our hypothesis was that improvement in clinical outcomes would be mirrored by beneficial changes in ventricular function and exercise capacity secondary to normalization of hemoglobin level.
Abstract and Introduction
Abstract
Background Anemia in heart failure is both common and associated with worse symptoms and increased mortality. Several small randomized controlled trials (RCTs) have assessed erythropoiesis-stimulating agents (ESAs), but definitive evaluation and clinical guidance are required. We sought to systematically review the effects of ESAs in chronic heart failure.
Methods An extensive search strategy identified 11 RCTs with 794 participants comparing any ESA with control over 2 to 12 months of follow-up. Published and additionally requested data were incorporated into a Cochrane systematic review (CD007613).
Results Nine studies were placebo controlled, and 5, double blinded. Erythropoiesis-stimulating agent treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2–188.4, P = .04) and 6-minute walk distance by 69.3 m (95% CI 17.0–121.7, P = .009) compared with control. Benefit was also noted for peak oxygen consumption (+2.29 mL/kg per minute, P = .007), New York Heart Association class (−0.73, P < .001), ejection fraction (+5.8%, P < .001), B-type natriuretic peptide (−226.99 pg/mL, P < .001), and quality-of-life indicators with a mean increase in hemoglobin level of 2 g/dL. There was a significantly lower rate of heart failure–related hospitalizations with ESA therapy (odds ratio 0.56, 95% CI 0.37–0.84, P = .005). No associated increase in adverse events or mortality (odds ratio 0.58, 95% CI 0.34–0.99, P = .047) was observed, although the number of events was limited.
Conclusion Meta-analysis of small RCTs suggests that ESA treatment can improve exercise tolerance, reduce symptoms, and have benefits on clinical outcomes in anemic patients with heart failure. Confirmation requires larger, well-designed studies with careful attention to dose, attained hemoglobin level, and long-term outcomes.
Introduction
Anemia in patients with chronic heart failure (CHF) is common, occurring in up to half of all patients depending on the population studied and the definition applied. Meta-analysis of >150,000 patients with CHF has identified that low hemoglobin level nearly doubles the risk of all-cause mortality over a 6-month to 5-year follow-up period, irrespective of whether CHF is due to systolic or diastolic dysfunction. Thus, anemia in CHF presents a therapeutic target with the potential for considerable improvement in clinical outcomes.
Erythropoiesis-stimulating agents (ESAs) are an established treatment of anemia in chronic kidney disease and cancer, although recent concerns have been raised over safety, particularly when titrated to a high hemoglobin level. However, the benefit of ESAs on quality of life in chronically ill patients is well documented. Erythropoietin as a treatment of anemia in patients with CHF has been studied in several small randomized controlled trials (RCTs) using a variety of preparations and doses. An overall benefit for reduced hospitalization has been noted, but the mechanism for this improvement is still unclear. There are also conflicting data on the effects of ESAs on exercise capacity, functional status, and mortality in patients with CHF, all of which are key issues in determining the cost-effectiveness of routine clinical administration of erythropoietin.
We sought to clarify these issues and determine the overall benefit and potential harm of ESA therapy in anemic patients with CHF using available RCTs. A range of outcomes were examined to fully understand the effects and mechanism of action. These included subjective and objective assessments of symptoms (quality-of-life measures and New York Heart Association [NYHA] classification) as well as functional and numerical evaluation of left ventricular exercise capacity and ejection fraction. We also reviewed CHF-related hospital admissions, all-cause mortality, and major adverse effects of erythropoietin treatment, updating postpublication outcomes where data were available. Our hypothesis was that improvement in clinical outcomes would be mirrored by beneficial changes in ventricular function and exercise capacity secondary to normalization of hemoglobin level.
Source...