3.3 Effect of erythropoiesis- stimulating agents and iron

3.3.2 Chronic heart failure

Evidence Statements for Cancer (erythropoiesis-stimulating agents)
Evidence Statements –
chronic heart failure (erythropoiesis-stimulating agents)
Evidence Consistency Clinical impact Generalisability Applicability
ES3.13 In anaemic patients with CHF, the effect of ESAs on mortality is uncertain. X X
ES3.14 In anaemic patients with CHF, the effect of ESAs on transfusion requirements is uncertain. X NA X X
ES3.15 In anaemic patients with CHF, the effect of ESAs on the incidence of thromboembolic events is uncertain. NA
ES3.16 In anaemic patients with CHF, ESAs may improve functional or performance status compared with no ESAs.
Evidence Statements for Chronic heart failure (iron therapy)
Evidence Statements –
chronic heart failure (iron therapy)
Evidence Consistency Clinical impact Generalisability Applicability
ES3.17 In CHF patients with iron deficiency, the effect of IV iron on mortality is uncertain. NA
ES3.18 In CHF patients (NYHA functional classes II or III) with iron deficiency (absolute and functional), IV iron improves functional or performance status, independent of Hb concentration.

CHF, chronic heart failure; ES, evidence statement; ESA, erythropoiesis-stimulating agent; Hb, haemoglobin; IV, intravenous; NYHA, New York Heart Association

=A; =B; =C; X=D; NA,not applicable (see Table 2.1)

Recommendation – chronic heart failure
R3

Grade B

In patients with CHF, identification and treatment of iron deficiency (absolute and functional) is recommended to improve functional or performance status.

This is consistent with the 2011 update to the Guidelines for the Prevention, Detection and Management of Chronic Heart Failure in Australia, 2006.2

Note: The studies reviewed only included patients treated with IV iron, and of NYHA functional classes II or III.

CHF, chronic heart failure; IV, intravenous; NYHA, New York Heart Association; R, recommendation

Erythropoiesis-stimulating agents – chronic heart failure

One systematic review (Level I), which included a large subset of patients with diabetes and congestive cardiac failure, found that ESA therapy was associated with reduced mortality.103 In a separate systematic review, the incidence of thromboembolic events, mortality and heart failure-related hospitalisations were not affected by ESAs,104 but there was a significant improvement in exercise tolerance. ESAs are not currently listed on the PBS for reimbursement for patients with cardiac failure.

Intravenous iron – chronic heart failure

Iron deficiency is common in patients with CHF, and is usually associated with anaemia.

Two RCTs (Level II), one of good quality15 and one of poor quality,105 evaluated the use of IV iron therapy in patients with CHF (New York Heart Association (NYHA) class II or III). Both studies included anaemic and nonanaemic patients who were likely to have either absolute iron deficiency (ferritin <100 mcg/L) or FID (ferritin 100 – 300 mcg/L with a transferrin saturation of 20%).

There was no significant difference in mortality between patients treated with IV iron and patients who did not receive IV iron, including after meta-analysis; however, the studies were underpowered. Neither study reported the incidence or volume of blood transfusion. Both studies showed a significant improvement in NYHA classification with IV iron.

The good-quality, multicentre RCT by Anker et al included CHF patients with absolute iron deficiency and FID, with Hb concentrations of 95 – 135 g/L.15 The study demonstrated reduced symptoms and improved submaximal exercise tolerance and quality of life with use of IV ferric carboxymaltose compared to a placebo. Improvements were independent of Hb concentrations. There was no significant difference between IV iron and the placebo in the rates of hospitalisation for any cardiovascular cause or for vascular disorders.

It is important to look for and treat iron deficiency in patients with CHF to reduce symptoms and improve exercise tolerance and quality of life. This advice has been incorporated as a Grade B recommendation in the 2011 update to the Guidelines for the Prevention, Detection and Management of Chronic Heart Failure in Australia, from the National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand.2