Amir Qaseem, MD, PhD, MHA; Linda L. Humphrey, MD, MPH; Nick Fitterman, MD; Melissa Starkey, PhD; Paul Shekelle, MD, PhD; for the Clinical Guidelines Committee of the American College of Physicians *
Note: Clinical practice guidelines are “guides” only and may not apply to all patients and clinical situations. Thus, they are not intended to override clinicians’ judgment. All ACP clinical practice guidelines are considered automatically withdrawn or invalid 5 years after publication or once an update has been issued.
Disclaimer: The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the U.S. Department of Veterans Affairs.
Financial Support: Financial support for the development of this guideline comes exclusively from the ACP operating budget.
Potential Conflicts of Interest: Dr. Shekelle: Grants: Agency for Healthcare Research and Quality, Veterans Affairs, Centers for Medicare & Medicaid Services, Office of the National Coordinator for Health Information Technology; Personal fees: ECRI Institute, Veterans Affairs, UpToDate. All other authors have no disclosures. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1830. A record of conflicts of interest is kept for each Clinical Guidelines Committee meeting and conference call and can be viewed at www.acponline.org/clinical_information/guidelines/guidelines/conflicts_cgc.htm.
Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Qaseem and Starkey: 190 N. Independence Mall West, Philadelphia, PA 19106.
Dr. Humphrey: Oregon Health and Science University, 3710 SW U.S. Veterans Hospital Road, Portland, OR 97201.
Dr. Fitterman: Huntington Hospital, 270 Park Avenue, Huntington, NY 11743.
Dr. Shekelle: West Los Angeles Veterans Affairs Medical Center, 11301 Wilshire Boulevard, Los Angeles, CA 90073.
Author Contributions: Conception and design: A. Qaseem, N. Fitterman, P. Shekelle.
Analysis and interpretation of the data: A. Qaseem, L.L. Humphrey, N. Fitterman, M. Starkey.
Drafting of the article: A. Qaseem, N. Fitterman, M. Starkey.
Critical revision of the article for important intellectual content: A. Qaseem, L.L. Humphrey, N. Fitterman, M. Starkey, P. Shekelle.
Final approval of the article: A. Qaseem, L.L. Humphrey, N. Fitterman, P. Shekelle.
Statistical expertise: A. Qaseem.
Administrative, technical, or logistic support: A. Qaseem, M. Starkey.
Collection and assembly of data: A. Qaseem.
This article has been corrected. The original version (PDF) is appended to this article as a supplement.
The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the treatment of anemia and iron deficiency in adult patients with heart disease.
This guideline is based on published literature in the English language on anemia and iron deficiency from 1947 to July 2012 that was identified using MEDLINE and the Cochrane Library. Literature was reassessed in April 2013, and additional studies were included. Outcomes evaluated for this guideline included mortality; hospitalization; exercise tolerance; quality of life; and cardiovascular events (defined as myocardial infarction, congestive heart failure exacerbation, arrhythmia, or cardiac death) and harms, including hypertension, venous thromboembolic events, and ischemic cerebrovascular events. The target audience for this guideline includes all clinicians, and the target patient population is anemic or iron-deficient adult patients with heart disease. This guideline grades the evidence and recommendations using the ACP's clinical practice guidelines grading system.
ACP recommends using a restrictive red blood cell transfusion strategy (trigger hemoglobin threshold of 7 to 8 g/dL compared with higher hemoglobin levels) in hospitalized patients with coronary heart disease. (Grade: weak recommendation; low-quality evidence)
ACP recommends against the use of erythropoiesis-stimulating agents in patients with mild to moderate anemia and congestive heart failure or coronary heart disease. (Grade: strong recommendation; moderate-quality evidence)
Table 1. The American College of Physicians Guideline Grading System
Table 2. Evidence for the Effects of RBC Transfusions, ESAs and IV Iron for the Treatment of Anemia in Patients With Heart Disease
Summary of the American College of Physicians guideline on treatment of anemia in patients with heart disease.
ACE = angiotensin-converting enzyme; CHD = coronary heart disease; CHF = congestive heart failure; ESA = erythropoiesis-stimulating agent; MI = myocardial infarction; NYHA = New York Heart Association.
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Alberto Palazzuoli, MD, PhD
University of Siena
January 15, 2014
We would like to respond to the recommendations for anemia treatment recently published in your journal that in our opinion deserves particular attention. The document concludes against the use of blood transfusions in patients with mild to moderate anemia. The use of erythropoiesis-stimulating agents (ESA) appears to increase the rate of thromboembolic and stroke events. (1)On the other hand Intravenous Iron administration improves quality of life and exercise tolerance. However, epidemiologic data showed that iron deficiency in HF is found in about half the CHF patients and more often in anemics than non anemic.Regarding ESA administration we would underline some aspects that do not emerge from the current and previous meta-analysis published in the Journal: (2)In the active arms ESA were sometimes administered together with iron in different dosages and different modalities. This could have had an impact on the results of the meta-analysis.The mean ESA dosage administration appears persistently higher as in the STAMINA as in the RED HF Trial respect to single center studies reported in the meta-analysis.(3) Especially if we contemplate the mean hemoglobin levels in the two Trials (11.5 gr/dl).(3,4)One third of patients recruited in the largest ESA Trial in HF anemic patients (RED-HF) had atrial fibrillation, a clinical condition that predisposes to peripheral and cerebral embolic events. Again, the prevalence of hypertensive patients was more than 70%. (4) All these points could explain the increased rate of adverse events in the active arm. Two other previous meta-analysis revealed different results: both studies showed a trend towards a decrease in hospitalization and improved exercise capacity in the active arm.(5,6) Moreover, there is now agreement that lower doses of ESA than were used in the STAMINA and RED HF studies should be used. In this context animal studies confirmed the ancillary effect of ESA: erythropoietin appears to increase vascular and endothelial grow factors after myocardial infarction, moreover it increases expression of heavy chain of myoglobin, nitric oxide liberation improving oxygen transport. (7) Most of these beneficial effects occur independently from the dose of ESA and appear only partially related to hematocrit improvement.(8) All these concerns raise several questions that should be better elucidated: the optimal hemoglobin intervention target is unknown; the clinical characteristic of patients and their co-morbidities should be better specified. In summary, there is a need to know the exact criteria for anemia definition in HF patients as well as the exact disorder of erythroid metabolism before writing the term “end” for ESA administration in anemic heart disease patients.1- Qaseem A, Humprey LL, Fitteman N, Starkey M, Shekelle P. Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians Ann Int Med 2013;159:770-7792- Kansagara D, Dyer E, Englnder H, Fu R, Freeman M, Kagen D. treatment of anemia in patients with heart disease: a systematic review. Ann Intern Med 2013; 159:746-7573- Swedberg K, Young BJ, Anand IS, Cheng S Desai AS, Diaz R, Maggioni AP et al. Treatment of anemia with darbapoetin alfa in systolic heart failure. New Engl J Med 2013; 368:1210-194- Ghali JK, Anand IS, Abraham WT, Fonarow GC, Greenberg B, Krum H, Massie BM et al. Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation. 2008;117:526-355- Kotecha D, Ngo K, Walters JA, Manzano L, Palazzuoli A, Flather MD Erythropoietin as a treatment of anemia in heart failure: systematic review of randomized trials. Am Heart J. 2011 ;161:822-831.6- van der Meer P, Groenveld HF, Januzzi JL Jr, van Veldhuisen DJ Erythropoietin treatment in patients with chronic heart failure: a meta-analysis. Heart. 2009 ;95:1309-14 7- Lipsic E, Westenbrink D, van der Meer P, van der Harst P, Voors AA, van Veldhuise D et al. Low dose erythropoietin improves cardiac function in experimental heart failure without increasing hematocrit. Eur J Heart Fail 2008; 10: 22-298- Mueller C, Wodack K, Twelker K, Werner N, Custodis F, Nickenig G. Darbepoetin improves endothelial function and increases circulating endothelial progenitor cell number in patients with coronary artery disease. Heart. 2011 ;97:1474-8
Qaseem A, Humphrey LL, Fitterman N, Starkey M, Shekelle P, for the Clinical Guidelines Committee of the American College of Physicians. Treatment of Anemia in Patients With Heart Disease: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2013;159:770–779. doi: 10.7326/0003-4819-159-11-201312030-00009
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Published: Ann Intern Med. 2013;159(11):770-779.
Cardiology, Guidelines, Hematology/Oncology, High Value Care, Hospital Medicine.
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