A Review of the Evidence: Treatment of Anemia in Patients with Heart Disease

Anemia is very common in patients with heart disease. About one-third of patients with congestive heart failure (CHF) and 10% to 20% of those with coronary heart disease (CHD) are anemic. Anemia in patients with CHF and CHD is associated with poorer outcomes, including an increased risk of hospitalization, decreased exercise capacity, and poor quality of life. Despite the association with poorer outcomes, it is unclear whether treating anemia or iron deficiency will improve outcomes. Anemia treatment strategies in heart failure and CHD patients include erythropoiesis-stimulating agents (ESAs work to stimulate bone marrow to produce red blood cells) and red blood cell transfusions. Iron replacement in iron deficient patients with or without anemia also has been investigated.

Investigators at the VA Evidence-based Synthesis Program in Portland, OR conducted a review of the literature from 1947 through November 2010 to evaluate the balance of benefit and harms of treatments for anemia among patients with heart disease, in particular, chronic heart failure or coronary heart disease (i.e., acute coronary syndrome, post-acute coronary syndrome, history of myocardial infarction, or angina). After screening more than 2,400 articles, 49 studies (28 of which were randomized controlled trials) were reviewed in detail to answer the following three key questions:

Question #1
In patients with CHF or CHD, what are the health benefits and harms of treating anemia with erythropoiesis-stimulating agents (ESAs)?

• Anemia is common in patients with heart disease, but the evidence base to date does not support a role for ESAs for anemia correction. Overall, investigators found little good quality evidence that ESA use consistently improves health outcomes (e.g., quality of life, exercise duration and tolerance).
• ESA use is associated with serious harms (e.g., mortality, vascular thrombosis) in patients with chronic kidney disease, a common comorbidity in those with CHF.

Question #2
In patients who have CHF or CHD and co-existing iron deficiency (with or without anemia), what are the health benefits and harms of using iron supplementation?

• Intravenous iron treatment improves exercise tolerance and quality of life in patients with symptomatic heart failure and low iron stores. This evidence is based primarily on a large trial of patients with NYHA (New York Heart Association) III heart failure and low ferritin (protein that binds to iron) levels.
• The impact on distal health outcomes (i.e., mortality and cardiovascular events) remains untested, as do the long-term effects of such treatment.

Question #3
In patients with CHF or CHD, what are the health benefits and harms of treating anemia with red blood cell transfusions?

• The role of blood transfusions remains unclear due to a limited number of small studies in limited settings.
• Nine RCTs, most of which were small and conducted in the perioperative setting, found that a conservative policy limiting transfusions to patients with a hemoglobin level below 7-9 g/dL was as safe as transfusing patients at a higher hemoglobin threshold, most often 10 g/dL.
• In addition, 21 observational studies examined transfusion in patients undergoing percutaneous coronary intervention (PCI) - or those admitted with acute coronary syndrome, MI, or decompensated heart failure. Inconsistent findings and methodological weakness complicated the interpretation of results. Findings suggest that transfusion has no benefit and may be harmful in patients with heart disease and hemoglobin >10g/dL. Transfusion is consistently associated with higher mortality risk in the unselected PCI population, across multiple studies with mean nadir hemoglobin of 8-9 g/dL.

Suggestions for Future Research
Ongoing studies, such as RED-HF (Reduction of Events with Darbepoetin alfa in Heart Failure), should be able to more clearly define whether or not there is a role for ESAs in the treatment of anemic heart failure patients. More research is needed on treatment of anemic patients with ischemic heart disease (IHD). In addition, more trials are needed to clarify whether and when blood transfusions provide benefit in patients with heart failure or ischemic heart disease.

This report is a product of the HSR&D Evidence-based Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers -- and to disseminate these reports throughout VA.

Reference
Kansagara D, Dyer E, Englander J, Kagen D, and Freeman M. Treatment of Anemia in Patients with Heart Disease: A Systematic Review. VA-ESP Project #05-225;2011.

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This report is a product of the HSR&D Evidence-Based Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers - and to disseminate these reports throughout VA.

See the full reports online.