Abstract Body (Do not enter title and authors here): Background and Aim: Iron deficiency (ID) is a common condition worldwide, affecting about one-third of the population, and is particularly prevalent in heart failure (HF) patients. In HF, ID worsens symptoms such as fatigue and shortness of breath, contributing to higher hospitalization rates and mortality. Intravenous (IV) iron therapies like Ferric Carboxymaltose (FCM) and Ferric Derisomaltose (FDI) have effectively enhanced symptoms and improved quality of life. This meta-analysis examines the safety and efficacy of these iron treatments.

Methods: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to May 2024 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. Our protocol was registered with PROSPERO (CRD#CRD42023469246). Our study included Randomized Controlled Trials (RCTs). The primary outcomes of our study includes major adverse events such as Cardiovascular Mortality, All-Cause Death, heart failure hospitalization rate, KCCQ, LVEF, MLHFQ3, and Peak Oxygen Consumption (pVO2).

Results: Twenty-four RCTs with 11,333 participants were analyzed. The pooled analysis indicated that All-cause mortality risk reduction was observed with FCM [RR=0.89; 95% CI: 0.75–1.04] and FDI [RR=0.95; 95% CI: 0.81–1.12]. FCM significantly reduced composite outcomes of hospitalization for HF or cardiovascular mortality [HR=0.74; 95% CI: 0.59–0.93], while FDI showed modest effects [HR=0.86; 95% CI: 0.56–1.26]. Kansas City Cardiomyopathy Questionnaire scores improved notably with FCM [MD=5.21; 95% CI: 2.22–8.19]. Left Ventricular Ejection Fraction improvement was highest with Iron Sucrose [MD=2.92; 95% CI: 1.61–4.21]. For the Minnesota Living with Heart Failure Questionnaire (MLHFQ), Iron Sucrose also showed the most improvement [MD = -18.00; 95% CI: -38.52 to 2.52], followed by FCM and FDI. In peak oxygen consumption (pVO2), FCM exhibited modest benefits [MD = 1.25; 95% CI: -2.34 to 4.84]. The six-minute walk test (6MWT) results identified Ferrous Sulphate as the most effective [MD = 53; 95% CI: -18.85 to 124.85], followed by FCM.

Conclusion: This highlights Ferric Carboxymaltose as a promising iron therapy for heart failure patients with iron deficiency. However, clinical decisions should consider patient factors, tolerability, and cost-effectiveness. Further long-term studies are needed to optimize treatment and prevent hospitalization.