Date of publication: June 29, 2017

News & Views

ERA-EDTA 2017: Updates on the safety of IV iron and the role of iron beyond renal anaemia

The benefits and risks of IV iron therapy were again a topic of discussion at the recent ERA-EDTA 2017 congress, with data on IV iron’s positive effects in heart failure patients also highlighted. This summary provides an overview of the relevant sessions from the congress.

The benefits and risks of IV iron therapy

A clinical symposium entitled ‘Iron – the bright and the dark side’ included a presentation by Jolanta Malyszko on the importance of iron, the physiology of iron overload and the need for balance, while Iain Macdougall discussed the concept of positive iron balance with IV iron in haemodialysis. Prof Macdougall showed that although iron accumulation in the liver has been found with IV iron therapy, this has not been shown to be associated with adverse outcomes; and no increased deposition was found in the myocardium. Studies to date have been inconclusive with regards to safety, but the hope is that the PIVOTAL trial will provide some clarification. Both Dr Malyszko and Prof Macdougall highlighted the conclusion that a positive iron balance does not equate to iron toxicity but might be required to overcome the hepcidin block in heavily inflamed patients.

Gunter Weiss’ presentation ‘Is iron fuel on the fire?’ in patients with infections supported the need for iron balance, highlighting that both iron deficiency and iron overload are detrimental in situations of infection, and calling for the avoidance of under and over treatment with iron therapy.

A poster by Dr Drozdz and colleagues analysed the effects on outcomes of two approaches to achieving KDIGO haemoglobin targets in haemodialysis patients; in dialysis centres in Poland the use of iron and doses of IV iron is 35% higher than in Portugal (p<0.001) while the use and doses of ESA is 17% higher in Portugal (5034 vs 3133 IU (adjusted)/week, p<0.001). Despite the contrasting treatment strategies, the authors found no significant differences in hospitalizations or mortality.[1]

A secondary analysis of the ‘Treatment for renal anaemia on prognosis in haemodialysis patients’ (TRAP) study highlighted the lack of conclusive evidence regarding the safety of IV iron. Presented during an oral communication, the data showed that, irrespective of ESA dose, higher doses of iron were associated with higher risk for cerebro-cardiovascular disease (CCVD) in CKD patients on maintenance haemodialysis.[2]

IV iron as a potential therapy beyond renal anaemia

Iron is present in many processes, including in ATP production in muscles. ERA-EDTA 2017 included presentations and discussion of the potential role of IV iron therapy outside the field of renal anaemia.

In a symposium sponsored by Vifor Fresenius Medical Care Renal Pharma, the panel discussed and presented data around the role of iron beyond that of renal anaemia management and erythropoiesis, particularly in patients with heart failure.3 The session highlighted data on ferric carboxymaltose (FCM) from the FAIR-HF, CONFIRM-HF and EFFECT-HF trials:

  • FAIR-HF: FCM significantly improved quality of life, Patient Global Assessment (PGA) score and NYHA functional class vs placebo
  • CONFIRM-HF: FCM reduced risk of hospitalisation due to worsening heart failure, resulted in sustained improvements in 6 Minute Walk Test (6MWT), distance, fatigue, quality of life, PGA and NYHA functional class vs placebo
  • EFFECT-HF: FCM treatment significantly improved exercise capacity vs placebo

Dr Comin-Colet also discussed the 2016 ESC guidelines which recommend the use of IV FCM in patients with heart failure and reduced ejection fraction (HFrEF) and iron deficiency to alleviate HF symptoms and improve exercise capacity and quality of life.

Two posters also looked at the role of IV iron in HFrEF patients. These meta-analyses examined the effect of IV FCM on hospitalization and mortality in iron-deficient HFrEF patients and renal dysfunction (eGFR <60mL/min/1.73m2).[4,5]

In the first poster, by Dr Piotr Ponikowski et al, IV FCM was associated with significantly lower rate of cardiovascular-related hospitalization and cardiovascular mortality vs placebo (0.56, 95% CI [0.34; 0.92], p=0.023). Treatment with IV FCM was not associated with an increased risk of adverse events, when compared to placebo: the incidence per 100 patient-years at risk of any treatment adverse events was 137.7 with FCM and 173.3 with placebo.[4]

In the second poster, using data from the same studies, Dr Ponikowski and colleagues examined the effect of IV FCM on functional capacity, symptoms and quality of life. The data reported showed significant improvements in 6MWT distance, NYHA functional class and EQ-5D VAS scale from week 4 and sustained through to week 24 with IV FCM treatment vs placebo. There were no significant differences in adverse event reporting.[5]

References

  1. [MP424] Consequences of achieving KDIGO anemia targets by different strategies; a European multicenter analysis. Maciej Drozdz et al. ERA-EDTA 2017 Congress
  2. [SO023] The impact of dose of ESA and iron on the risk of adverse events of hemodialysis patients. Takahiro Kuragano et al. ERA-EDTA 2017 Congress
  3. Is there a role for iron beyond erythropoiesis in patients with chronic kidney disease? Symposium – ERA-EDTA 2017 Congress
  4. [MP415] Effect of intravenous iron therapy with ferric carboxymaltose on outcomes in iron-deficient patients with renal dysfunction and heart failure with reduced ejection fraction: an individual patient data meta-analysis of four randomized, double-blind trials. Piotr Ponikowski et al. ERA-EDTA 2017 Congress
  5. [MP417] Impact of intravenous ferric carboxymaltose iron therapy on symptoms and functionality in iron-deficient patients with heart failure with reduced ejection fraction and renal dysfunction: an individual patient data meta-analysis of 4 randomized, double-blind trials. Piotr Ponikowski et al. ERA-EDTA 2017 Congress

 

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