Physicians' Academy for Cardiovascular Education

Effects of i.v. iron therapy in patients with systolic heart failure and iron deficiency

Jankowska EA, et al. Eur J Heart Fail. 2016 (epub)


Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials

Jankowska EA, Tkaczyszyn M, Suchocki T, et al.
Eur J Heart Fail. 2016;18:786-95; Epub 2016 Jan 28
 

Background

In patients with stable heart failure (HF), iron deficiency (ID) is a common co-morbidity, occurring in 50% of patients and in ~46% of non-anaemic patients with stable systolic HF[1].
When ID is present, it has been shown that symptoms worsen and exercise capacity and quality of life (QoL) of patients with systolic HF impair [1, 2-4].
Patients with HF and ID have a high mortality and higher urgent hospitalizations due to HF progression [1, 2]. Therefore, treatment of ID in patients with HF is expected to be beneficial.
The effects of intravenous (i.v.) iron therapie in ID patients with HF has been studied in several trials [5-10].
This meta-analysis aimed to summarize the evidence of i.v. iron therapy in ID patients with systolic HF.
An aggregate data meta-analysis of randomized controlled trials (published up to September 2014) regarding i.v. iron therapy in patients with systolic HF and ID was performed.
Five trials were identified which fulfilled the inclusion criteria (851 patients, 509 received i.v. iron therapy) [5-7, 9, 10].
 

Main results

  • Intravenous iron therapy in patients with systolic HF and ID reduced the risk of the combined endpoint of all-cause death or cardiovascular hospitalization [OR 0.44, 95% CI 0.30–0.64, P<0.0001], and the combined endpoint of cardiovascular death or hospitalization for worsening HF (OR 0.39, 95% CI 0.24–0.63, P=0.0001).
  • The analysis showed no effect on either all-cause or cardiovascular mortality, which may be due to a low number of reported deaths [n=20 (4%) vs. n=19 (6%) for those treated vs. not treated with i.v. iron] and relatively short follow-up
  • Intravenous iron therapy resulted in a reduction in NYHA class (data are reported as a mean net effect with 95% CIs for all continuous variables) (−0.54 class, 95% CI −0.87 to −0.21, P=0.001); an increase in 6-min walking test distance (+31 m, 95% CI 18–43, P<0.0001); and an improvement in quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ) score +5.5 points, 95% CI 2.8–8.3, P<0.0001; European Quality of Life–5 Dimensions (EQ-5D) score +4.1 points, 95% CI 0.8–7.3, P=0.01; Minnesota Living With Heart Failure Questionnaire (MLHFQ) score −19 points, 95% CI:–23 to −16, P<0.0001; and Patient Global Assessment (PGA) +0.70 points, 95% CI 0.31–1.09, P=0.0004].
  • Results were consistent in both anaemic and non-anaemic patients.
 

Conclusion

Intravenous iron therapy applied in iron-deficient patients with systolic HF, regardless of concomitant anaemia, improves outcomes, alleviates HF symptoms, and improves exercise capacity and QoL.
This meta-analysis therefore recommends treating these patients with intravenous iron.
 
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References

1. Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, BanasiakW, Lok DJ, Rosentryt P, Torrens A, Polonski L, van Veldhuisen DJ, van der Meer P, Jankowska EA. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 2013;165:575–582.e3
2. Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, Banasiak W, Polonski L, Filippatos G, McMurray JJ, Anker SD, Ponikowski P. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J 2010;31:1872–80.
3. Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, von Haehling S, Doehner W, Banasiak W, Polonski L, Filippatos G, Anker SD, Ponikowski P. Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure. J Card Fail 2011;17:899–906.
4. Enjuanes C, Klip IT, Bruguera J, Cladellas M, Ponikowski P, Banasiak W, van Veldhuisen DJ, van der Meer P, Jankowska EA, Comín-Colet J. Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol 2014;174:268–275.
5. Toblli JE, Lombraña A, Duarte P, Di Gennaro F. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol 2007;50:1657–1665.
6. Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Roughton M, Foldes G, Thum T, Majda J, Banasiak W, Missouris CG, Poole-Wilson PA, Anker SD, Ponikowski P. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial. J Am Coll Cardiol 2008;51:103–112.
7. Beck-da-Silva L, Piardi D, Soder S, Rohde LE, Pereira-Barretto AC, de Albuquerque D, Bocchi E, Vilas-Boas F, Moura LZ, Montera MW, Rassi S, Clausell N. IRON-HF study: a randomized trial to assess the effects of iron in heart failure patients with anemia. Int J Cardiol 2013;168:3439–3442.
8. Comín-Colet J, Ruiz S, Cladellas M, Rizzo M, Torres A, Bruguera J. A pilot evaluation of the long-term effect of combined therapy with intravenous iron sucrose and erythropoietin in elderly patients with advanced chronic heart failure and cardio-renal anemia syndrome: influence on neurohormonal activation and clinical outcomes. J Card Fail 2009;15:727–735.
9. Anker SD, Comin Colet J, Filippatos G,Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P; FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436–2448.
10. Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, McDonagh T, Parkhomenko A, Tavazzi L, Levesque V, Mori C, Roubert B, Filippatos G, Ruschitzka F, Anker SD; CONFIRM-HF Investigators. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J 2015;36:657–668.