A recent review addresses the lack of clinical trials conducted to assess the clinical efficacy of the full range of intravenous iron products currently available, and highlights the potential drawbacks of giving unverified products to highly vulnerable populations such as patients with heart failure (HF).
Patients with chronic heart failure have a high prevalence of iron deficiency – the leading cause of anemia. While oral iron supplements are not always effective in these patients, iron products given intravenously are known to correct both iron deficiency and iron deficiency anemia, thereby also alleviating heart failure symptoms, along with improving exercise capacity and quality of life. The European Society of Cardiology (ESC) guidelines on heart failure recommend treating iron-deficient patients with intravenous ferric carboxymaltose (FCM), based on this compound’s clinical efficacy versus placebo in two randomized controlled trials (FAIR-HF and CONFIRM-HF).
The currently available intravenous iron compounds differ mainly in terms of the carbohydrate molecule used to stabilize the polynuclear Fe(III)-oxyhydroxide/oxide core. This compound-specific carbohydrate strongly influences the product’s physico-chemical properties, determining the metabolic fate of the complex, its pharmacokinetic/pharmacodynamic profile and its interactions with the innate immune system. Despite these clear differences, robust study data in terms of clinical efficacy are only available for FCM.
Differences in clinical safety and efficacy
Martin-Malo et al. therefore evaluated published clinical and non-clinical studies conducted with FCM and five other intravenous iron products. They identified the differences between the intravenous iron products in terms of clinical safety/tolerability and efficacy, and determined whether the differences in their physico-chemical properties affected clinical outcome. They also determined whether the considerable data supporting the clinical efficacy of FCM in CHF patients can be extrapolated to other intravenous iron products that lack comparable study data.
…substituting one product for another carries danger of severe adverse events
Their findings clearly indicate that this is not the case. Not only does substituting one product for another carry the danger of severe adverse events, the differences between products are clearly acknowledged by the regulatory authorities. The European Medicines Agency and the US Food and Drug Administration both recommend evaluation of the therapeutic evidence of intravenous iron products.
The authors conclude that the various intravenous iron products on the market differ greatly in terms of physico-chemical characteristics, which possibly influences their pharmacological activities. Also, without head-to-head clinical studies proving the therapeutic equivalence between other intravenous iron products and FMC, extrapolation of results and substitution with a different intravenous iron product is not recommended in heart failure patients.
Original article: ESC Heart Failure 2019;6:241-253.
Author: Sally Hill