-
1.
Treating Iron Deficiency (ID) Anemia in Heart Failure (HF) Patients with IV Iron: A Meta-Analysis
Ogugua, F. M., Aguilar, F. A., Gamam, A., Maqsood, M. H., Yoo, T. K., Kasmi, F., AlKowatli, O., Lo, K.
Cureus. 2023;15(7):e41895
Abstract
Findings on the effects of iron on heart failure (HF) hospitalizations and mortality among patients with iron deficiency (ID) and HF remain conflicting across different studies. We performed a meta-analysis of clinical trials assessing the clinical, hematic and cardiovascular benefits of treating ID in HF patients. We completed a systematic search for studies comparing IV iron to placebo in HF patients with ID. The primary outcomes were rates of HF hospitalization and all-cause mortality. Secondary outcomes included change in hematic values, New York Heart Association (NYHA) class and ejection fraction. We applied a random-effects model with planned sensitivity analyses of studies with skewed effect sizes. Nine studies were included with a total of 2,261 patients. Analysis revealed that treatment of HF patients with IV iron replacement significantly reduced the odds of HF hospitalization (odds ratio (OR): 0.44; 95% confidence interval (CI): 0.24 to 0.78; p=0.005, I(2)=67%),) but did not significantly impact all-cause mortality compared to placebo (OR: 0.89; 95%, CI: 0.67 to 1.19; p=0.44, I(2): 0%). Analysis showed that IV iron treatment group had significantly higher serum ferritin, transferrin saturation and hemoglobin (Hb) levels. They also had lower NYHA class -1.90 (95% CI (-2.91 to -0.89); p<0.001, I(2):89%) with higher ejection fraction 0.50 (95% CI (0.09 to 0.90) p=0.016, I(2):86%). Treatment with IV iron in HF patients with ID is associated with a significant reduction of HF hospitalization but no effects on all-cause mortality. There were also significant increases in hematic values and ejection fraction with a reduction in NYHA class.
-
2.
Comparison of revascularization and conservative treatment for hemorrhagic moyamoya disease in East Asian Countries: a single-center case series and a systematic review with meta-analysis
Zhang, X. H., He, J. H., Zhang, X. S., Zhang, J., Wang, C. J., Dong, Y. P., Tao, W.
Frontiers in neurology. 2023;14:1169440
Abstract
OBJECTIVE The optimal treatment approach for hemorrhagic moyamoya disease (HMMD) remains a topic of debate, particularly regarding the comparative efficacy of revascularization versus conservative treatment. Our study, which included a single-center case series and a systematic review with meta-analysis, aimed to determine whether surgical revascularization is associated with a significant reduction in postoperative rebleeding, ischemic events, and mortality compared to conservative treatment among East Asian HMMD patients. METHODS We conducted a systematic literature review by searching PubMed, Google Scholar, Wanfang Med Online (WMO), and the China National Knowledge Infrastructure (CNKI). The outcomes of surgical revascularization and conservative treatment, including rebleeding, ischemic events and mortality, were compared. The authors' institutional series of 24 patients were also included and reviewed in the analysis. RESULTS A total of 19 East Asian studies involving 1,571 patients as well as our institution's retrospective study of 24 patients were included in the study. In the adult patients-only studies, those who underwent revascularization had significantly lower rates of rebleeding, ischemic events, and mortality compared to those who received conservative treatment (13.1% (46/352) vs. 32.4% (82/253), P < 0.00001; 4.0% (5/124) vs. 14.9% (18/121), P = 0.007; and 3.3% (5/153) vs. 12.6% (12/95), P = 0.01, respectively). In the adult/pediatric patients' studies, similar statistical results of rebleeding, ischemic events, and mortality have been obtained (70/588 (11.9%) vs. 103/402 (25.6%), P = 0.003 or <0.0001 in a random or fixed-effects model, respectively; 14/296 (4.7%) vs. 26/183 (14.2%), P = 0.001; and 4.6% (15/328) vs. 18.7% (23/123), P = 0.0001, respectively). CONCLUSION The current single-center case series and systematic review with meta-analysis of studies demonstrated that surgical revascularization, including direct, indirect, and a combination of both, significantly reduces rebleeding, ischemic events, and mortality in HMMD patients in the East Asia region. More well-designed studies are warranted to further confirm these findings.
-
3.
Improvement in left atrial strain following ferric carboxymaltose in heart failure: an analysis of the Myocardial-IRON trial
Santas, E., Del Canto, I., Cardells, I., Miñana, G., Llàcer, P., Almenar, L., Fácila, L., Maceira, A. M., Sanchis, J., Núñez, J.
ESC heart failure. 2023
Abstract
AIMS: Iron deficiency (ID) is associated with an impaired cardiac function and remodelling in heart failure (HF). Treatment with ferric carboxymaltose (FCM) has been showed recently to improve biventricular systolic function and ventricular strain parameters in patients with HF with reduced ejection fraction and ID, but there is no evidence on the benefit of FCM on the left atrium (LA). In this study, we aimed to evaluate the effect of FCM on LA longitudinal strain (LA-LS). METHODS AND RESULTS This is a post hoc subanalysis of a double-blind, placebo-controlled, randomized clinical trial that enrolled 53 ambulatory patients with HF, left ventricular ejection fraction (LVEF) < 50%, and ID [Myocardial-IRON trial (NCT03398681)], treated with FCM or placebo. Cardiac magnetic resonance-featured tracking (CMR-FT) strain changes were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. The median age of the sample was 68 years (interquartile range: 64-76), and 20 (69%) were men. Mean ± standard deviation of LVEF was 39 ± 11%, and most (97%) were in stable New York Heart Association class II. At baseline, mean LA-LS was -8.9 ± 3.5%. At 30 days, and compared with placebo, LA-LS significantly improved in those allocated to FCM treatment arm (LA-LS = -12.0 ± 0.5 and -8.5 ± 0.6, respectively; - ∆ 3.55%, P < 0.001). CONCLUSIONS In patients with stable HF, LVEF < 50%, and ID, treatment with FCM was associated with short-term improvements in LA-LS assessed by CMR-FT. Future works should assess the potential benefit of iron repletion on LA function.
-
4.
Effects of Intravenous Iron Replacement Therapy on Cardiovascular Outcomes in Patients with Heart Failure: A Systematic Review and Meta-Analysis
Reinhold, J., Burra, V., Corballis, N., Tsampasian, V., Matthews, G., Papadopoulou, C., Vassiliou, V. S.
Journal of Cardiovascular Development and Disease. 2023;10(3)
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.
-
5.
The impact of ferric derisomaltose on cardiovascular and non-cardiovascular events in patients with anemia, iron deficiency and heart failure with reduced ejection fraction
Ray, R., Ford, I., Cleland, J. G. F., Graham, F., Ahmed, F. Z., Al-Mohammad, A., Cowburn, P. J., Critoph, C., Kalra, P. A., Lane, R. E., et al
Journal of cardiac failure. 2023
Abstract
BACKGROUND In some countries, intravenous (IV) ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of intravenous FDI in a subgroup of patients with anemia in the IRONMAN trial. METHOD AND RESULTS IRONMAN enrolled patients with heart failure, left ventricular ejection fraction (LVEF) ≤45% and iron deficiency (ferritin <100 µg/L or TSAT <20%), 771 (68%) of whom had anemia (hemoglobin <12 g/dL for women; <13 g/dL for men). Patients were randomized, open-label, to FDI (n=397) or usual care (n=374) and followed for a median of 2.6 years. The primary endpoint, recurrent hospitalization for heart failure and cardiovascular death, occurred less frequently for those assigned to FDI (rate ratio 0.78 [95% CI 0.61 - 1.01); p=0.063). First-event analysis for cardiovascular death or hospitalization for heart failure, less affected by the COVID pandemic, gave similar results (hazard ratio 0.77 [95% CI 0.62 - 0.96]; p=0.022). Patients randomized to FDI reported a better Minnesota Living with Heart Failure quality-of-life, for overall (p = 0.013) and physical-domain (p = 0.00093) scores at four months. CONCLUSION In patients with iron deficiency anemia and heart failure with reduced LVEF, IV FDI improves quality of life and may reduce cardiovascular events.
-
6.
Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials
Hamed, M., Elseidy, S. A., Ahmed, A., Thakker, R., Mansoor, H., Khalili, H., Mohsen, A., Mamas, M. A., Banerjee, S., Kumbhani, D. J., et al
Heliyon. 2023;9(6):e17245
Abstract
BACKGROUND Randomized clinical trials (RCTs) evaluating the role of intravenous (IV) iron administration in patients with heart failure (HF) and iron deficiency (ID) have yielded inconsistent results. METHODS Electronic search of MEDLINE, EMBASE and OVID databases was performed until November 2022 for RCTs that evaluated the role of IV iron administration in patients with HF and ID. The main study outcomes were the composite of HF hospitalization or cardiovascular mortality, and individual outcome of HF hospitalization. Summary estimates were evaluated using random effects model. RESULTS The final analysis included 12 RCTs with 3,492 patients (1,831 patients in the IV iron group and 1,661 patients in the control group). The mean follow-up was 8.3 months. IV iron was associated with a lower incidence in the composite of HF hospitalization or cardiovascular mortality (31.9% vs. 45.3%; relative risk [RR] 0.72; 95% confidence interval [CI] 0.59-0.88) and individual outcome of HF hospitalization (28.4% vs. 42.2; RR 0.69; 95% CI 0.57-0.85). There was no significant difference between both groups in cardiovascular mortality (RR 0.88; 95% CI 0.75-1.04) and all-cause mortality (RR 0.95; 95% CI 0.83-1.09). IV iron was associated with lower New York Heart Association class and higher left ventricular ejection fraction (LVEF). Meta-regression analyses showed no effect modification for the main outcomes based on age, hemoglobin level, ferritin level or LVEF. CONCLUSION Among patients with HF and ID, IV iron administration was associated with reduction in the composite of HF hospitalization or cardiovascular mortality and driven by a reduction in HF hospitalization.
-
7.
Standard of care versus Octreotide in Angiodysplasia-related bleeding (the OCEAN study): A Multicenter Randomized Controlled trial
Goltstein, L. C. M. J., Grooteman, K. V., Bernts, L. H. P., Scheffer, R. C. H., Laheij, R. J. F., Gilissen, L. P. L., Schrauwen, R. W. M., Talstra, N. C., Zuur, A. T., Braat, H., et al
Gastroenterology. 2023
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND AND AIMS Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We aimed to investigate the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least four red blood cell (RBC) units and/or parental iron infusions in the year preceding randomization. Patients were allocated (1:1) to 40mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was one year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least one octreotide injection or followed standard of care for at least one month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS We enrolled 62 patients (mean age 72 years, 32 males) from 17 Dutch hospitals in the octreotide (n=31) and standard of care (n=31) groups. Patients required a mean number of 20.3 (SD 15.6) transfusion units and 2.4 (SD 2.0) endoscopic procedures in the year before enrolment. The total number of transfusions was lower with octreotide (11.0; 95% CI, 5.5-16.5) compared to standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSION Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS gov, NCT02384122.
PICO Summary
Population
Patients with refractory anemia due to bleeding gastrointestinal angiodysplasias, enrolled in the OCEAN randomised controlled trial (n= 62).
Intervention
Octreotide (n= 31).
Comparison
Standard of care (n= 31).
Outcome
The treatment duration was one year. The primary outcome was the mean difference in the number of transfusion units (red blood cell + parental iron) between the octreotide and standard of care groups. The total number of transfusions was lower with octreotide (11.0; 95% CI [5.5, 16.5]) compared to standard of care (21.2; 95% CI [15.7, 26.7]). Octreotide reduced the mean number of transfusion units by 10.2; 95% CI [2.4, 18.1]. Octreotide reduced the annual volume of endoscopic procedures by 0.9; 95% CI [0.3, 1.5].
-
8.
Effect of Intravenous Iron-Carbohydrate Complexes in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: A Meta-analysis of Randomized Controlled Trials
Mototani R, Watanabe A, Kuno T, Briasoulis A
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese. 2023
-
9.
Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalisation: A European multinational economic evaluation
McEwan P, Harrison C, Binnie R, Lewis RD, Cohen-Solal A, Lund LH, Ohlsson M, von Haehling S, Comin-Colet J, Pascual-Figal DA, et al
European journal of heart failure. 2023
Abstract
AIMS: Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalisations and improved quality of life when used to treat ID at discharge in patients hospitalised for acute HF with left-ventricular ejection fraction of <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. METHODS AND RESULTS The per country eligible population was calculated, aligning with the ESC 2021 HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalisation episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13,237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalisations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5,215 in Sweden to 205,630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within one year. CONCLUSIONS This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realised through implementation of the ESC HF guideline recommendations regarding ID treatment. This article is protected by copyright. All rights reserved.
-
10.
Efficacy of Ferric carboxymaltose in heart failure with iron deficiency: an individual patient data meta-analysis
Ponikowski, P., Mentz, R. J., Hernandez, A. F., Butler, J., Khan, M. S., van Veldhuisen, D. J., Roubert, B., Blackman, N., Friede, T., Jankowska, E. A., et al
European heart journal. 2023
-
-
-
Free full text
-
-
Editor's Choice
Abstract
BACKGROUND AND AIMS Whereas a beneficial effect of intravenous ferric carboxymaltose (FCM) on symptoms and exercise capacity among patients with iron deficiency (ID) and heart failure (HF) has been consistently demonstrated, the effects of treatment on clinical events remain the subject of research. This meta-analysis aimed to characterize the effects of FCM therapy on hospitalizations and mortality. METHODS Patient-level data from randomized, placebo-controlled FCM trials including adults with HF and ID with ≥52 weeks follow-up were analysed. The co-primary efficacy endpoints were (1) composite of total/recurrent cardiovascular hospitalizations and cardiovascular death, and (2) composite of total HF hospitalizations and cardiovascular death, through 52 weeks. Key secondary endpoints included individual composite endpoint components. Event rates were analysed using a negative binomial model. Treatment-emergent adverse events were also examined. RESULTS Three FCM trials with a total of 4501 patients were included. FCM was associated with a significantly reduced risk of co-primary endpoint 1 (rate ratio [RR] 0.86; 95% confidence interval [CI] 0.75-0.98; P=0.029; Cochran Q: 0.008), with a trend towards a reduction of co-primary endpoint 2 (RR 0.87; 95% CI 0.75-1.01; P=0.076; Cochran Q: 0.024). Treatment effects appeared to result from reduced hospitalization rates, not improved survival. Treatment appeared to have a good safety profile and was well-tolerated. CONCLUSIONS In iron-deficient patients with HF with reduced left ventricular ejection fraction, intravenous FCM was associated with significantly reduced risk of hospital admissions for HF and cardiovascular causes, with no apparent effect on mortality.
PICO Summary
Population
Adults with heart failure (HF) and iron deficiency enrolled in the ferric carboxymaltose (FCM) trials: CONFIRM-HF, AFFIRM-AHF, and HEART-FID (3 randomised controlled trials, n= 4,501).
Intervention
FCM (n= 2,251).
Comparison
Placebo (n= 2,250).
Outcome
The co-primary efficacy endpoints were (1) composite of total/recurrent cardiovascular hospitalizations and cardiovascular death, and (2) composite of total HF hospitalizations and cardiovascular death, through 52 weeks. FCM was associated with a significantly reduced risk of co-primary endpoint 1 (rate ratio [RR] 0.86; 95% confidence interval (CI) [0.75, 0.98]; Cochran Q: 0.008), with a trend towards a reduction of co-primary endpoint 2 (RR 0.87; 95% CI [0.75, 1.01]; Cochran Q: 0.024).