Effects of Intravenous Iron Replacement Therapy on Cardiovascular Outcomes in Patients with Heart Failure: A Systematic Review and Meta-Analysis

Abstract

(1) Background: Iron deficiency (ID) is an important adverse prognostic marker in patients with heart failure (HF); however, it is unclear whether intravenous iron replacement reduces cardiovascular mortality in this patient group. Here, we estimate the effect of intravenous iron replacement therapy on hard clinical outcomes following the publication of IRONMAN, the largest trial in this field. (2) Methods: In this systematic review and meta-analysis, prospectively registered with PROSPERO and reported according to PRISMA guidelines, we searched PubMed and Embase for randomized controlled trials investigating intravenous iron replacement in patients with HF and co-existing ID. The primary outcome was cardiovascular mortality and secondary outcomes were all-cause mortality, hospitalizations for HF and a combination of the primary outcome and hospitalizations for HF. (3) Results: A total of 1671 items were identified and after removal of duplicates we screened titles and abstracts of 1202 records. Some 31 studies were identified for full-text review and 12 studies were included in the final review. The odds ratio (OR) for cardiovascular death using a random effects model was 0.85 (95% CI 0.69 to 1.04) and for all-cause mortality it was 0.83 (95% CI 0.59 to 1.15). There was a significant reduction in hospitalizations for HF (OR 0.49, 95% CI 0.35 to 0.69) and the combination of hospitalizations for HF and cardiovascular death (OR 0.65, 95% CI 0.5 to 0.85). (4) Conclusions: This review supports the use of IV iron replacement reducing hospitalization rates for HF, however more research is required to determine the effect on cardiovascular mortality and to identify the patient population most likely to benefit.

High-dose intravenous iron use in hemodialysis patients: Results from the National Health Insurance System (2019–2020) in South Korea

“…IV iron supplementation has bene cial effects in patients with heart failure, suggesting that iron acts directly on heart function (22). The possible mechanism may involve the important role of iron in cellular oxygen storage and cell metabolism in cardiomyocytes with a high energy demand (23).…”

“…RCTs have shown that IV iron improves exercise capacity and quality of life (24,25). In a meta-analysis of 12 RCTs of patients with heart failure, IV iron administration reduced hospitalization rate for heart failure, but the association with cardiovascular death was not signi cant (22). The PIVOTAL trial showed that high-dose IV iron resulted in a signi cantly lower risk of major nonfatal cardiovascular events compared with a lowdose regimen among HD patients (13).…”

Iron Status and Short-Term Recovery after Non-Severe Acute Myocarditis: A Prospective Observational Study

“…Recently, experimental models have demonstrated that the detrimental impact of iron deficiency on cardiac muscle can be reversed via iron supplementation [ 11 , 35 , 36 ]. In addition, clinical data have confirmed beneficial effects of iron supplementation in iron-deficient subjects in chronic conditions [ 37 , 38 ]. In patients with heart failure with left ventricular dysfunction, intravenous iron therapy leaded to improvement of symptoms, exercise capacity, and quality of life in randomized clinical trials, and was even associated with better prognosis in further meta-analysis [ 37 , 38 ].…”

“…In addition, clinical data have confirmed beneficial effects of iron supplementation in iron-deficient subjects in chronic conditions [ 37 , 38 ]. In patients with heart failure with left ventricular dysfunction, intravenous iron therapy leaded to improvement of symptoms, exercise capacity, and quality of life in randomized clinical trials, and was even associated with better prognosis in further meta-analysis [ 37 , 38 ]. Recently, clinical data have shown favorable results of treatment of iron depletion in a post-acute clinical scenario: in patients who were stabilized after an episode of acute heart failure, a treatment with ferric carboxymaltose reduced the risk of heart failure hospitalizations in a randomized clinical trial [ 39 ].…”