Management of Iron Deficiency and Anemia in Patients with Heart Disease

Educational Objectives

The goal of this lecture is to improve management of iron deficiency in patients with heart failure. After hearing and assimilating this program, the clinician will be better able to:

1. Recognize iron deficiency in patients with heart failure.

2. Prescribe an effective regimen for oral iron supplementation.

3. Adhere to AABB practice guidelines for red blood transfusions in a variety of patients.

Summary

Introduction: iron important for O2 transport and storage and oxidative metabolism; iron deficiency common, and results in significant decrease in maximum O2 consumption (Vo2max; peak aerobic capacity)

Iron deficiency in heart failure (HF): ≈50% of patients with HF have iron deficiency (partly because of chronic inflammation and increased levels of hepcidin [hormone that signals intestine to stop absorbing iron]); affects quality of life, exercise tolerance, cognitive function, and survivability; ≈40% of patients with iron deficiency have anemia; incidence of iron deficiency and iron deficiency anemia increases over time with worsening HF; effect of iron deficiency independent of anemia (ie, iron deficiency without anemia associated with significant increase in mortality), but iron deficiency with anemia associated with worse outcomes; ≈28% of patients with HF undergo iron studies; only 8.5% of patients found to be iron deficient receive iron supplementation; definitions of iron deficiency in HF — ferritin <100 ng/mL; transferrin saturation <20% if ferritin 100 to 300 ng/mL

Guidelines: in patients with HF, check for anemia and check iron status (independent concerns); anemia — if patient anemic, look for causes other than iron deficiency; check vitamin B12, folic acid, renal function, thyroid function, and occult bleeding; iron studies — iron; total iron-binding capacity (TIBC); ferritin; transferrin saturation — if ≤20%, check ferritin (if ferritin ≥300 ng/mL, no iron supplementation needed; if ≤300 ng/mL, treat with iron supplementation); if transferrin saturation ≥20%, check ferritin (if ferritin <100 ng/mL, treat with iron supplementation; if >300 ng/mL, no treatment needed; if ferritin 100-300 ng/mL, use clinical judgment)

Intravenous (IV) iron: much safer than in past; many formulations available (use clinical judgment based on individual patient); meta-analysis — IV iron in patients with HF with reduced ejection fraction (HFrEF) associated with ≈55% reduced risk for all-cause mortality or cardiovascular (CV) hospitalization, and ≈60% reduction in risk for CV death or hospitalization for worsening HF; no statistically significant improvement in death alone (may be attributable to small size and short duration of studies); IV iron associated with improvement in morbidities (eg, 6-min walk test, New York Heart Association classification); ferric carboxymaltose — probably best-studied form; probably most expensive; can be given in single dose; well-tolerated; systematic review saw ≈40% decrease in composite outcome of mortality and hospitalization with ferric carboxymaltose, with trend toward improvement in all-cause mortality; iron sucrose — easy to dose, but must be given over time (usually in 2 doses, 1 wk apart); associated with improvements in laboratory values, peak aerobic capacity, hospital admission, ejection fraction, and quality of life

Oral iron: trial using oral iron polysaccharide (150 mg twice daily) in patients with HFrEF saw no improvement in peak Vo2 at 16 wk or in 6-min walk test; new data suggest oral iron should not be used multiple times per day, or daily; study comparing daily dosing to twice-daily dosing saw decrease in fractional iron absorption in both groups (ie, no difference between daily or twice-daily oral iron dosing); rate for adverse events (eg, nausea, vomiting, constipation) ≈70%; daily dosing vs alternate-day dosing — study saw higher fractional and total iron absorption with alternate-day dosing

Consequences of anemia in HF: peripheral vasodilation; decreased blood pressure; activation of catecholamines and decreased renal blood flow; increased salt and water retention; worsening left ventricular dysfunction and HF; “critical crit” — point at which insufficient O2 delivery causes organ system dysfunction; varies among individuals

Restrictive vs liberal blood transfusions: restrictive blood transfusion strategy associated with improved outcomes, use of less blood, and trend toward improvement in mortality, myocardial infarction (MI), congestive HF, rebleeding, pneumonia, and thromboembolism; AABB guideline for hemoglobin levels that should trigger transfusion — for stable hospitalized patients, use restrictive transfusion strategy with hemoglobin transfusion trigger of 7 g/dL; for postoperative patients, ≈8 g/dL; for patients in intensive care unit, 7 g/dL; for patients with preexisting CV disease ≈8 g/dL; FOCUS and TRICC trials showed restrictive transfusion strategy used less blood; active cardiac disease — CRIT Randomized Pilot Study of 45 patients with acute MI and hematocrit <30% saw that patients randomized to liberal transfusion strategy (hematocrit goal 30%-33%) had more in-hospital death, recurrent MI, and new or worsening CHF (≈38% vs 13%) than did those treated according to conservative transfusion strategy (hematocrit goal 24%-27%); in Myocardial Ischemia and Transfusion Trial of 110 patients with acute coronary syndrome and hemoglobin <10 g/dL undergoing percutaneous coronary intervention, liberal transfusion (hemoglobin goal >10 g/dL) group had lower rate of 30-day death, MI, or unscheduled revascularization (1% vs 29%) compared to conservative transfusion group (hemoglobin goal >8 g/dL); data conflicting, so best management of patients with acute coronary syndrome unclear

Readings

Carson JL et al: Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J. 2013 Jun;165(6):964-971.e1; Cooper HA et al: Conservative versus liberal red cell transfusion in acute myocardial infarction (the CRIT Randomized Pilot Study). Am J Cardiol. 2011 Oct 15;108(8):1108-11; Hébert PC: Transfusion requirements in critical care. The TRICC trial: a focus on the sub-group analysis. Vox Sang. 2002 Aug;83 Suppl 1:387-96; Jankowska EA et al: Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail. 2016 Jul;18(7):786-95; Moretti D et al: Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015 Oct 22;126(17):1981-9; Stoffel NU et al: Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017 Nov;4(11):e524-e533; Tobian AA et al: Red blood cell transfusion: 2016 clinical practice guidelines from AABB. Transfusion. 2016 Oct;56(10):2627-2630.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Rohde reported nothing to disclose. The planning committee reported nothing to disclose.

Acknowledgements

Dr. Rohde spoke in Bellaire, MI, at the 54th Annual Northern Michigan Family Medicine Update, presented June 18-22, 2018, by Michigan Medicine, Department of Family Medicine. For more information about courses from this sponsor, please visit ocpd.med.umich.edu/cme.  The Audio Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

FP670101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.