IV Iron for Patients With HFrEF and Iron Deficiency: Efficacy, Outcomes, and Future Directions

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Recent studies highlight the growing interest surrounding the use of IV iron for patients with HFrEF and iron deficiency.

Heart failure (HF) remains a significant global health challenge, prompting ongoing research into effective treatments. Intravenous (IV) iron therapy has emerged as a potential treatment, particularly for patients with HF with reduced ejection fraction (HFrEF) and concurrent iron deficiency (ID). Recent studies and guidelines, including a focused update by the European Society of Cardiology (ESC), highlight the growing interest and mixed findings in this area.

The ESC’s 2021 Guideline for the Management of Heart Failure strongly recommends (1A) IV iron for patients with HFrEF and ID. However, the efficacy and impact of IV iron therapy are still under scrutiny, with randomized controlled trials (RCTs) providing varied results. Two systematic reviews sought to synthesize the evidence and provide a clearer understanding of IV iron therapy’s role in this patient population.^1,2

Following the 2021 guideline updates, researchers reviewed 15 RCTs involving 6,649 patients to evaluate IV iron’s effect on patient-based outcomes.¹ The study team conducted a thorough search of EMBASE and PubMed, and two reviewers independently performed data extraction. Primary outcomes focused on QOL, while secondary outcomes included first HF hospitalizations and all-cause mortality. Data were pooled using a random-effects model.¹

The results showed that IV iron significantly improved QOL (standardized mean difference, -1.36) and reduced first HF hospitalizations (HR, 0.73). However, it did not significantly impact all-cause mortality (HR, 0.90). The certainty of these findings ranged from moderate to very low, emphasizing the need for well-designed RCTs to confirm these results and better understand the impact on mortality.

In a similar study, researchers analyzed RCTs with 6,614 patients to assess the efficacy of IV iron therapy.² The authors compared IV iron therapy to standard care in patients with HF and ID. Primary outcomes were the combined rate of HF hospitalizations or cardiovascular mortality, individual HF hospitalizations, and all-cause, HF, and cardiovascular mortalities. Secondary outcomes included New York Heart Association (NYHA) functional classification improvements, QOL, 6-minute walk test performance, left ventricular ejection fraction, and adverse events. The researchers used a random-effects model to calculate the relative risk (RR) or mean difference with 95% confidence intervals.²

Analysis of 14 randomized controlled trials indicated that IV iron therapy significantly reduced composite outcomes (RR: 0.84) and HF hospitalizations (RR: 0.74) compared with standard care. The study team did not observe a significant difference in mortality rates. Additionally, IV iron therapy improved NYHA functional classification, QOL, and 6-minute walk test outcomes without major impacts on left ventricular ejection fraction. Adverse events were consistent between the groups. ²

Overall, the authors determined that IV iron therapy showed promise for reducing HF hospitalizations while enhancing QOL and 6-minute walk test performance in patients with HF. However, its impact on all-cause and cardiovascular mortality remains limited. ²

Both studies support the potential of IV iron therapy to reduce HF hospitalizations and improve QOL for patients with HFrEF and ID. However, these studies also highlight its limited impact on all-cause mortality, underscoring the need for further research to better understand the therapy’s full benefits and optimize patient outcomes.