Intravenous iron in patients with heart failure and iron deficiency: an updated meta‐analysis

Graham, Fraser J; Pellicori, Pierpaolo; Kalra, Paul R.; Ford, Ian; Bruzzese, Dario; Cleland, John G.F.

doi:10.1002/ejhf.2810

Cited by 60 publications

(42 citation statements)

References 29 publications

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“…Overall, it may be beneficial to serially evaluate TSAT levels and treat to ensure levels are greater than 20%, irrespective of ferritin, to provide mortality benefits. From a therapeutic perspective, a recent meta-analysis, involving 10 studies and a total of 3373 participants, reported that IV iron supplementation in patients with HFrEF has a strong signal for a favorable effect on cardiovascular mortality with IV iron (odds ratio 0.86; 95% CI 0.70 to 1.05; p = 0.14) and a weaker signal for all-cause mortality (odds ratio 0.93; 95% CI 0.78 to 1.12; p = 0.47), but the current evidence was inconclusive and larger trails with longer follow-up would be needed [ 14 ]. Of note, in the same meta-analysis, patients with transferrin saturation <20% benefited more from iron therapy vs. those with higher saturation, but the interaction for this difference did not reach statistical significance and needs to be interpreted with caution [ 14 ].…”

Section: Discussionmentioning

confidence: 91%

“…This is important, as recent data suggest a beneficial effect of IV iron supplementation on HF hospitalizations in patients with HF. A recent meta-analysis suggests that iron therapy, in the form of repeat IV doses, leads to a substantial ~25% reduction in HF hospitalizations in patients with HFrEF [ 14 ]. This meta-analysis included a total of 3373 participants from 10 trials, and approximately 50% were assigned to IV iron therapy.…”

Section: Discussionmentioning

confidence: 99%

“…These results emphasize the ability of a less commonly evaluated iron metabolism biomarker to communicate multiple facets of a patient’s well-being. Of note, IV iron therapy, in addition to a substantial favorable effect on HF hospitalizations (and potentially, cardiovascular mortality), improves exercise capacity and quality of life, independently of anemia correction [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Despite the encouraging results of a recent meta-analysis on the effect of IV iron therapy for iron-deficient patients with HF [ 14 ], several questions regarding this form of therapy remain unanswered. For example, the evidence for patients with HFpEF is limited to subgroup analyses from clinical trials that did not specify LVEF-based entry criteria, and the total number of patients with HFpEF in those studies was small.…”

Section: Discussionmentioning

confidence: 99%

“…Most recently, the IRONMAN trial, which evaluated a rapid IV iron supplementation strategy as a mean to reduce hospital resources utilization for IV iron supplementation, demonstrated a neutral impact of IV iron on cardiovascular death and an encouraging but statistically borderline effect on HF hospitalizations [ 13 ]. However, an updated meta-analysis of IV iron supplementation trials in HF, including the results of IRONMAN, demonstrated a clear effect on HF hospitalizations but not on CV or all-cause mortality [ 14 ]. Oral iron supplementation on the other hand, is not supported by the current evidence, given the lack of benefit in patients with HF, likely secondary to poor absorption of oral iron and its inability to replete the iron stores in these patients [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Markers of Iron Metabolism and Outcomes in Patients with Heart Failure: A Systematic Review

Dhaliwal

Καλογερόπουλος

2023

IJMS

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Iron deficiency (ID) in conjunction with heart failure (HF) poses a challenge for clinicians and is associated with worse HF outcomes. Treatment of ID with IV iron supplementation for patients with HF has demonstrated benefits in quality of life (QoL) and HF-related hospitalizations. The aim of this systematic review was to summarize the evidence linking iron metabolism biomarkers with outcomes in patients with HF to assist in the optimal use of these biomarkers for patient selection. A systematic review of observational studies in English from 2010 to 2022 was conducted using PubMed, with keywords of “Heart Failure” and respective iron metabolism biomarkers (“Ferritin”, “Hepcidin”, “TSAT”, “Serum Iron”, and “Soluble Transferrin Receptor”). Studies pertaining to HF patients, with available quantitative data on serum iron metabolism biomarkers, and report of specific outcomes (mortality, hospitalization rates, functional capacity, QoL, and cardiovascular events) were included, irrespective of left ventricular ejection fraction (LVEF) or other HF characteristics. Clinical trials of iron supplementation and anemia treatment were removed. This systematic review was conducive to formal assessment of risk of bias via Newcastle-Ottawa Scale. Results were synthesized based on their respective adverse outcomes and iron metabolism biomarker(s). Initial and updated searches identified 508 unique titles once duplicates were removed. The final analysis included 26 studies: 58% focused on reduced LVEF; age range was 53–79 years; males composed 41–100% of the reported population. Statistically significant associations of ID were observed with all-cause mortality, HF hospitalization rates, functional capacity, and QoL. Increased risk for cerebrovascular events and acute renal injury have also been reported, but these findings were not consistent. Varying definitions of ID were utilized among the studies; however, most studies employed the current European Society of Cardiology criteria: serum ferritin < 100 ng/mL or the combination of ferritin between 100–299 ng/mL and transferrin saturation (TSAT) < 20%. Despite several iron metabolism biomarkers demonstrating strong association with several outcomes, TSAT better predicted all-cause mortality, as well as long-term risk for HF hospitalizations. Low ferritin was associated with short-term risk for HF hospitalizations, worsening functional capacity, poor QoL, and development of acute renal injury in acute HF. Elevated soluble transferrin receptor (sTfR) levels were associated with worse functional capacity and QoL. Finally, low serum iron was significantly associated with increased risk for cardiovascular events. Considering the lack of consistency among the iron metabolism biomarkers for association with adverse outcomes, it is important to incorporate additional biomarker data, beyond ferritin and TSAT, when assessing for ID in HF patients. These inconsistent associations question how best to define ID to ensure proper treatment. Further research, potentially tailored to specific HF phenotypes, is required to optimize patient selection for iron supplementation therapy and appropriate targets for iron stores replenishment.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Markers of Iron Metabolism and Outcomes in Patients with Heart Failure: A Systematic Review

Dhaliwal

Καλογερόπουλος

2023

IJMS

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Iron Deficiency and Incident Heart Failure in Older Community‐Dwelling Individuals

Sharma,

Katz,

Chaves

et al. 2024

ESC Heart Failure

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AimsAmong persons with prevalent heart failure (HF), iron deficiency has been linked to HF admissions, and intravenous iron replacement improves HF outcomes. Recent studies in persons with chronic kidney disease (CKD) demonstrate that iron deficiency is associated with incident HF. This study aimed to determine the relationship of iron status with incident HF in community‐dwelling older adults irrespective of their kidney function.MethodsIn this case‐cohort study, 1,006 Cardiovascular Health Study participants (785 from the random sub‐cohort [including 193 HF cases] and 221 additional HF cases [N = 414 total HF cases]) aged ≥ 65 years without HF (41% with CKD), we used weighted Cox models to evaluate associations of iron status with incident HF. Participants were categorized based on quartiles of transferrin saturation and ferritin as “iron replete” (27.3%), “functional iron deficiency” (7.7%), “iron deficiency” (11.8%), “mixed iron deficiency” (5.6%), “high iron” (9.3%) and “non‐classified” (38.1%), consistent with prior studies.ResultsCompared to older persons who were iron replete, those with iron deficiency were at higher risk of incident HF (HR 1.47; 1.02–2.11) in models adjusting for demographics, HF risk factors, and estimated glomerular filtration rate. Other iron categories did not associate with incident HF. The relationship of iron deficiency with incident HF did not differ by CKD status (interaction P value 0.2).ConclusionsAmong community‐dwelling elders, iron deficiency is independently associated with incident HF, an association that was similar irrespective of CKD status. Our findings support conduct of clinical trials of iron replacement for prevention of HF in older adults with iron deficiency.

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Intravenous iron and SGLT2 inhibitors in iron‐deficient patients with heart failure and reduced ejection fraction

Docherty,

McMurray,

Kalra

et al. 2024

ESC Heart Failure

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AimsTo explore the potential interaction between use of SGLT2 inhibitors and the increase in haemoglobin in patients randomized to intravenous iron or the control group in the IRONMAN (Effectiveness of Intravenous Iron Treatment versus Standard Care in Patients with Heart Failure and Iron Deficiency) trial.Methods and resultsThis was a post hoc exploratory analysis of the IRONMAN trial which randomized patients with heart failure, a left ventricular ejection fraction (LVEF) ≤ 45% and iron deficiency (transferrin saturation <20% or ferritin <100 μg/L) to open label intravenous ferric derisomaltose or usual care. Of the 1137 randomized patients, 29 (2.6%) were taking an SGLT2 inhibitor at baseline. The mean (SD) change in haemoglobin from baseline at 4 weeks in those taking an SGLT2 inhibitor at baseline was 1.3 (1.2) g/dL in patients randomized to ferric derisomaltose and 0.1 (0.7) g/dL in the usual care group; between‐group difference = 1.0 g/dL (95% CI 0.1, 1.8). The equivalent numbers in the no SGLT2 inhibitor group were 0.6 (0.9) g/dL in those randomized to ferric derisomaltose and 0.1 (0.8) g/dL in the usual care group; between‐group difference = 0.4 g/dL (95% CI 0.3, 1.6); interaction P value = 0.10. No patient receiving an SGLT2 inhibitor at baseline developed polycythaemia during follow‐up (defined as haemoglobin >16.5 g/dL [men] or >16 g/dL [women]).ConclusionsIn the IRONMAN trial, there was a trend to a greater increase in haemoglobin with ferric derisomaltose in iron‐deficient patients taking an SGLT2 inhibitor at baseline, as compared with those not taking one.

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Intravenous iron in patients with heart failure and iron deficiency: an updated meta‐analysis

Cited by 60 publications

References 29 publications

Markers of Iron Metabolism and Outcomes in Patients with Heart Failure: A Systematic Review

Markers of Iron Metabolism and Outcomes in Patients with Heart Failure: A Systematic Review

Iron Deficiency and Incident Heart Failure in Older Community‐Dwelling Individuals

Intravenous iron and SGLT2 inhibitors in iron‐deficient patients with heart failure and reduced ejection fraction

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