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Economic evaluation of ferric carboxymaltose compared with placebo in iron-deficient patients with heart failure: a systematic review
Rezapour A, Souresrafil A, Shamsaei M, Barzegar M, Tashakori-Miyanroudi M, Ketabchi E
International journal of clinical pharmacy. 2023
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Editor's Choice
Abstract
BACKGROUND It has been shown that ferric carboxymaltose (FCM) improves symptoms and quality of life in iron-deficient patients with heart failure (HF). AIM: We aimed to systematically review studies conducted on the cost-effectiveness of FCM compared to placebo in iron-deficient patients with HF. METHOD We searched PubMed, EMBASE, Scopus, and Web of Science to find the relevant studies. After removing duplicates, two authors independently evaluated the titles, abstracts, and full texts. We included studies that investigated the full economic evaluations of FCM in HF patients with iron deficiency (cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis) and used the CHEERS tool to evaluate the quality of the studies. RESULTS Seven studies were included which evaluated the economic analysis of treatments with FCM in iron-deficient patients with HF. The CHEERS scores for most of the studies (n = 6) were 0.77 or higher (very good quality). The lowest incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY) of FCM ($1801.96) was from Italy, and the highest ICER per QALY of FCM ($25,981.28) South Korea. Results of the studies showed that FCM, compared to placebo, was cost-effective in iron-deficient patients with HF. CONCLUSION FCM is a cost-effective treatment for iron-deficient patients with HF. Considering the fact that all the included studies in the present systematic review took place in high-income countries, we recommend further studies investigating the cost-effectiveness of FCM in low- and middle-income countries.
PICO Summary
Population
Iron-deficient patients with heart failure (HF), (7 studies).
Intervention
Ferric carboxymaltose (FCM).
Comparison
Placebo.
Outcome
The included studies investigated cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis, and used the CHEERS tool to evaluate the quality of the studies. The CHEERS scores for most of the studies (n = 6) were 0.77 or higher (very good quality). The lowest incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY) of FCM ($1,801.96) was from Italy, and the highest ICER per QALY of FCM ($25,981.28) South Korea. Results of the studies showed that FCM, compared to placebo, was cost-effective in iron-deficient patients with HF.
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Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia
Carson, J. L., Brooks, M. M., Hébert, P. C., Goodman, S. G., Bertolet, M., Glynn, S. A., Chaitman, B. R., Simon, T., Lopes, R. D., Goldsweig, A. M., et al
The New England journal of medicine. 2023
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Editor's Choice
Abstract
BACKGROUND A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level. METHODS In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days. RESULTS A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49). CONCLUSIONS In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.).
PICO Summary
Population
Adult patients with myocardial infarction and anaemia enrolled in the Myocardial Ischemia and Transfusion (MINT) trial (n= 3,504).
Intervention
Restrictive transfusion strategy (haemoglobin cutoff, 7 or 8 g per deciliter), (n= 1,749).
Comparison
Liberal transfusion strategy (haemoglobin cutoff, <10 g per deciliter), (n= 1,755).
Outcome
The primary outcome was a composite of myocardial infarction or death at 30 days. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean haemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1,749 patients (16.9%) in the restrictive-strategy group and in 255 of 1,755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval (CI), [0.99, 1.34]). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI [0.96, 1.47]); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI [0.94, 1.49]).
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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
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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].
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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
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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).
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Ferric Carboxymaltose in Heart Failure with Iron Deficiency
Mentz, R. J., Garg, J., Rockhold, F. W., Butler, J., De Pasquale, C. G., Ezekowitz, J. A., Lewis, G. D., O'Meara, E., Ponikowski, P., Troughton, R. W., et al
The New England journal of medicine. 2023
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Editor's Choice
Abstract
BACKGROUND Ferric carboxymaltose therapy reduces symptoms and improves quality of life in patients who have heart failure with a reduced ejection fraction and iron deficiency. Additional evidence about the effects of ferric carboxymaltose on clinical events is needed. METHODS In this double-blind, randomized trial, we assigned ambulatory patients with heart failure, a left ventricular ejection fraction of 40% or less, and iron deficiency, in a 1:1 ratio, to receive intravenous ferric carboxymaltose or placebo, in addition to standard therapy for heart failure. Ferric carboxymaltose or placebo was given every 6 months as needed on the basis of iron indexes and hemoglobin levels. The primary outcome was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. The significance level was set at 0.01. RESULTS We enrolled 3065 patients, of whom 1532 were randomly assigned to the ferric carboxymaltose group and 1533 to the placebo group. Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (Wilcoxon-Mann-Whitney P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients. The number of patients with serious adverse events occurring during the treatment period was similar in the two groups (413 patients [27.0%] in the ferric carboxymaltose group and 401 [26.2%] in the placebo group). CONCLUSIONS Among ambulatory patients who had heart failure with a reduced ejection fraction and iron deficiency, there was no apparent difference between ferric carboxymaltose and placebo with respect to the hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance. (Funded by American Regent, a Daiichi Sankyo Group company; HEART-FID ClinicalTrials.gov number, NCT03037931.).
PICO Summary
Population
Patients with heart failure and iron deficiency (n= 3,065).
Intervention
Intravenous ferric carboxymaltose group (n= 1,532).
Comparison
Placebo (n= 1,533).
Outcome
Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (unmatched win ratio, 1.10; 99% confidence interval [0.99, 1.23]). The number of patients with serious adverse events occurring during the treatment period was similar in the two groups: 413 patients (27.0%) in the ferric carboxymaltose group, and 401 (26.2%) in the placebo group.
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Efficacy of Therapeutic Apheresis for Cryoglobulinemic Vasculitis Patients with Renal Involvement: A Systematic Review
Miao, J., Krisanapan, P., Tangpanithandee, S., Thongprayoon, C., Cheungpasitporn, W.
Blood purification. 2023;:1-9
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Abstract
INTRODUCTION Therapeutic apheresis (TA) is commonly used for cryoglobulinemic vasculitis (CV) patients, but its efficacy remains uncertain. This systematic review aimed to assess the efficacy of different TA modalities, such as plasma exchange (PE), plasmapheresis (PP), and cryofiltration (CF), in treating CV patients with renal involvement. METHODS Literature search of MEDLINE, EMBASE, and Cochrane Databases was conducted up to December 2022. Studies that reported the outcomes of TA in adult CV patients with renal involvement were assessed. The protocol for this systematic review has been registered with PROSPERO (No. CRD42023417727). The quality of each study was evaluated by the investigators using the validated methodological index for non-randomized studies (minors) quality score. RESULTS 154 patients who encountered 170 episodes of serious events necessitating TA were evaluated across 76 studies. Among them, 51% were males, with a mean age ranging from 49 to 58 years. The CV types included 15 type I, 97 type II, and 13 type III, while the remaining patients exhibited mixed (n = 17) or undetermined CV types (n = 12). Among the treatment modalities, PE, PP, and CF were performed in 85 (56%), 52 (34%), and 17 patients (11%), respectively, with no identical protocol for TA treatment. The overall response rate for TA was 78%, with response rates of 84%, 77%, and 75% observed in type I, II, and III patients respectively. Most patients received steroids, immunosuppressants, and treatment targeting the underlying causative disease. The overall long-term renal outcome rate was 77%, with type I, II, and III patients experiencing response rates of 89%, 76%, and 90%, respectively. The renal outcomes in patients receiving PE, PP, and CF were comparable, with rates of 78%, 76%, and 81%, respectively. CONCLUSIONS This study presents compelling evidence that combination of TA with other treatments, especially immunosuppressive therapy, is a successful strategy for effectively managing severe renal involvement in CV patients. Among the TA modalities studied, including PE, PP, and CF, all demonstrated efficacy, with PE being the most frequently employed approach.
PICO Summary
Population
Cryoglobulinemic vasculitis (CV) patients with renal involvement (63 case reports and 13 case series, n= 154).
Intervention
Different therapeutic apheresis (TA) modalities: plasma exchange (PE), plasmapheresis (PP), and cryofiltration (CF).
Comparison
Outcome
A total of 154 patients experiencing 170 episodes of serious events that necessitated TA, were included in this systematic review. The CV type was classified as 15 type I cases, 97 type II cases, and 13 type III cases, while the remaining patients exhibited mixed (n= 17) or undetermined CV types (n= 12). Among the treatment modalities, PE, PP, and CF were performed in 85 (56%), 52 (34%), and 17 patients (11%), respectively, with no identical protocol for TA treatment. The overall response rate for TA was 78%, with response rates of 84%, 77%, and 75% observed in type I, II, and III patients respectively. Most patients received steroids, immunosuppressants, and treatment targeting the underlying causative disease. The overall long-term renal outcome rate was 77%, with type I, II, and III patients experiencing response rates of 89%, 76%, and 90%, respectively. The renal outcomes in patients receiving PE, PP, and CF were comparable, with rates of 78%, 76%, and 81%, respectively.
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Meta-Analysis and Metaregression of the Treatment Effect of Intravenous Iron in Iron-Deficient Heart Failure
Martens, P., Augusto, S. N., Jr., Mullens, W., Tang, W. H. W.
JACC. Heart failure. 2023
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Editor's Choice
Abstract
BACKGROUND Guidelines recommend that intravenous iron should be considered to improve symptoms of heart failure (HF) and reduce the risk for HF admissions in patients after acute HF. OBJECTIVES This study sought to analyze the effect of intravenous iron on cardiovascular (CV) death and HF admissions in a broad population of HF patients with iron deficiency and the relation with baseline transferrin saturation (TSAT). METHODS A systematic review of all published randomized controlled trials assessing the effect of intravenous iron in patients with iron deficiency and HF between January 1, 2000, and August 26, 2023, was performed. The overall treatment effect was estimated using a fixed effect model for: 1) CV death; 2) CV death and HF admission; 3) first HF admission; and 4) total HF admissions. Metaregression through a mixed effect model was used to explore the impact of baseline TSAT in case of heterogeneity among trial results. RESULTS A total of 14 randomized controlled trials were identified in the systematic review and retained in the meta-analysis. Aggregate-level data were included on 6,624 HF patients, 3,407 of whom were randomized to intravenous iron and 3,217 to placebo. Treatment with intravenous iron resulted in a lower risk for CV death (OR: 0.867 [95% CI: 0.755-0.955]; P = 0.0427), combined CV death and HF admission (OR: 0.838 [95% CI: 0.751-0.936]; P = 0.0015), first HF admission (OR: 0.855 [95% CI: 0.744-0.983]; P = 0.0281), and total HF admissions (rate ratio: 0.739 [95% CI: 0.661-0.827]; P < 0.0001). Significant heterogeneity among trial results was observed for first and total HF admissions. Metaregression suggested that some of the heterogeneity was related to the baseline TSAT of the enrolled population, with trials enrolling patients with lower TSAT exhibiting a large effect size on HF-related events. CONCLUSIONS The totality of data suggests that treatment with intravenous iron reduces both CV death and HF-related events in a broad population with HF. A lower baseline TSAT might be important for the effect on HF-related events.
PICO Summary
Population
Patients with iron deficiency and heart failure (HF), (14 randomised controlled trials, n= 6,624).
Intervention
Intravenous iron (n= 3,407).
Comparison
Placebo (n= 3,217).
Outcome
Treatment with intravenous iron resulted in a lower risk for cardiovascular (CV) death (OR: 0.867; 95% CI [0.755, 0.955]), combined CV death and HF admission (OR: 0.838; 95% CI [0.751, 0.936]), first HF admission (OR: 0.855; 95% CI [0.744, 0.983]), and total HF admissions (rate ratio: 0.739; 95% CI [0.661, 0.827]). Significant heterogeneity among trial results was observed for first and total HF admissions. Meta-regression suggested that some of the heterogeneity was related to the baseline transferrin saturation (TSAT) of the enrolled population, with trials enrolling patients with lower TSAT exhibiting a large effect size on HF-related events.
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8.
Systematic review and meta-analysis of intravenous iron-carbohydrate complexes in HFrEF patients with iron deficiency
Sindone A, Doehner W, Comin-Colet J
ESC heart failure. 2022
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Editor's Choice
Abstract
Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). The present meta-analysis evaluates the effect of intravenous (IV) iron-carbohydrate complex supplementation in patients with HF with reduced ejection fraction (HFrEF) and ID/iron deficiency anaemia (IDA). Randomized controlled trials (RCTs) comparing IV iron-carbohydrate complexes with placebo/standard of care in patients with HFrEF with ID/IDA were identified using Embase (from 1957) and PubMed (from 1989) databases through 25 May 2021. Twelve RCTs including 2381 patients were included in this analysis. The majority (90.8%) of patients receiving IV iron-carbohydrate therapy were administered ferric carboxymaltose (FCM); 7.5% received iron sucrose and 1.6% received iron isomaltoside. IV iron-carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42-0.65); P < 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59-0.95); P = 0.016], but did not significantly impact all-cause mortality, compared with control. IV iron-carbohydrate therapy significantly improved functional and exercise capacity compared with the control. There was no significant difference in outcome between IV iron-carbohydrate formulations when similar endpoints were measured. No significant difference in adverse events (AE) was observed between the treatment groups. IV iron-carbohydrate therapy resulted in improvements in a range of clinical outcomes and increased functional and exercise capacity, whereas AEs were not significantly different between IV iron-carbohydrate and placebo/standard of care arms. These findings align with the European Society of Cardiology's 2021 HF guidelines, which recommend the consideration of FCM in symptomatic patients with a left ventricular ejection fraction < 45% and ID.
PICO Summary
Population
Patients with heart failure (HF) with reduced ejection fraction (HFrEF) and iron deficiency, (12 randomised controlled trials, n= 2,381).
Intervention
Intravenous (IV) iron-carbohydrate complex supplementation.
Comparison
Placebo or standard of care.
Outcome
The majority (90.8%) of patients receiving IV iron-carbohydrate therapy were administered ferric carboxymaltose; 7.5% received iron sucrose and 1.6% received iron isomaltoside. IV iron-carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42-0.65)] and first hospitalization for worsening HF or death [0.75 (0.59-0.95)], but did not significantly impact all-cause mortality, compared with control. IV iron-carbohydrate therapy significantly improved functional and exercise capacity compared with the control. There was no significant difference in outcome between IV iron-carbohydrate formulations when similar endpoints were measured. No significant difference in adverse events (AE) was observed between the treatment groups. IV iron-carbohydrate therapy resulted in improvements in a range of clinical outcomes and increased functional and exercise capacity, whereas AEs were not significantly different between IV iron-carbohydrate and placebo/standard of care arms.
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9.
Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial
Kalra PR, Cleland JGF, Petrie MC, Thomson EA, Kalra PA, Squire IB, Ahmed FZ, Al-Mohammad A, Cowburn PJ, Foley PWX, et al
Lancet (London, England). 2022
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Editor's Choice
Abstract
BACKGROUND For patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year. We aimed to evaluate the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure. METHODS IRONMAN was a prospective, randomised, open-label, blinded-endpoint trial done at 70 hospitals in the UK. Patients aged 18 years or older with heart failure (left ventricular ejection fraction ≤45%) and transferrin saturation less than 20% or serum ferritin less than 100 μg/L were eligible. Participants were randomly assigned (1:1) using a web-based system to intravenous ferric derisomaltose or usual care, stratified by recruitment context and trial site. The trial was open label, with masked adjudication of the outcomes. Intravenous ferric derisomaltose dose was determined by patient bodyweight and haemoglobin concentration. The primary outcome was recurrent hospital admissions for heart failure and cardiovascular death, assessed in all validly randomly assigned patients. Safety was assessed in all patients assigned to ferric derisomaltose who received at least one infusion and all patients assigned to usual care. A COVID-19 sensitivity analysis censoring follow-up on Sept 30, 2020, was prespecified. IRONMAN is registered with ClinicalTrials.gov, NCT02642562. FINDINGS Between Aug 25, 2016, and Oct 15, 2021, 1869 patients were screened for eligibility, of whom 1137 were randomly assigned to receive intravenous ferric derisomaltose (n=569) or usual care (n=568). Median follow-up was 2·7 years (IQR 1·8-3·6). 336 primary endpoints (22·4 per 100 patient-years) occurred in the ferric derisomaltose group and 411 (27·5 per 100 patient-years) occurred in the usual care group (rate ratio [RR] 0·82 [95% CI 0·66 to 1·02]; p=0·070). In the COVID-19 analysis, 210 primary endpoints (22·3 per 100 patient-years) occurred in the ferric derisomaltose group compared with 280 (29·3 per 100 patient-years) in the usual care group (RR 0·76 [95% CI 0·58 to 1·00]; p=0·047). No between-group differences in deaths or hospitalisations due to infections were observed. Fewer patients in the ferric derisomaltose group had cardiac serious adverse events (200 [36%]) than in the usual care group (243 [43%]; difference -7·00% [95% CI -12·69 to -1·32]; p=0·016). INTERPRETATION For a broad range of patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric derisomaltose administration was associated with a lower risk of hospital admissions for heart failure and cardiovascular death, further supporting the benefit of iron repletion in this population. FUNDING British Heart Foundation and Pharmacosmos.
PICO Summary
Population
Patients with heart failure and iron deficiency enrolled in the IRONMAN trial in 70 UK hospitals (n= 1,137).
Intervention
Intravenous ferric derisomaltose (n= 569).
Comparison
Usual care (n= 568).
Outcome
Median follow-up was 2.7 years (IQR 1.8-3.6). 336 primary endpoints (22.4 per 100 patient-years) occurred in the ferric derisomaltose group and 411 (27.5 per 100 patient-years) occurred in the usual care group (rate ratio [RR] 0.82 [95% CI 0.66 to 1.02]). In the COVID-19 analysis, 210 primary endpoints (22.3 per 100 patient-years) occurred in the ferric derisomaltose group compared with 280 (29.3 per 100 patient-years) in the usual care group (RR 0.76 [95% CI 0.58 to 1.00]). No between-group differences in deaths or hospitalisations due to infections were observed. Fewer patients in the ferric derisomaltose group had cardiac serious adverse events (200 [36%]) than in the usual care group (243 [43%]; difference -7·00% [95% CI -12.69 to -1.32].
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10.
Comparison of multiple treatments in the management of transplant-related thrombotic microangiopathy: a network meta-analysis
Yang J, Xu X, Han S, Qi J, Li X, Pan T, Zhang R, Han Y
Annals of hematology. 2022
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Editor's Choice
Abstract
Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is a fatal post-transplant complication. It has a high mortality rate and worse prognosis, but treatment strategies remain controversial. We screened 6 out of 3453 studies on the treatment of TA-TMA. These investigations compared 5 treatment strategies with a network meta-analysis approach. The final outcome was the proportion of patients who responded to these therapies. There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities shows that rTM (recombinant human soluble thrombomodulin) is most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM (immunosuppression manipulation) rank 3 (32.24%), TPE (therapeutic plasma exchange) intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM have significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE having lower efficacy than all other TA-TMA therapies exception to supportive care. In our study, rTM and Eculizumab may be the best choice when treating TA-TMA.
PICO Summary
Population
Patients receiving treatment for transplantation-associated thrombotic microangiopathy (TA-TMA), (6 studies, n= 71).
Intervention
Therapeutic plasma exchange (TPE).
Comparison
Recombinant human soluble thrombomodulin (rTM). Eculizumab. Immunosuppression manipulation (ISM). Supportive care.
Outcome
There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities showed that rTM was most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM rank 3 (32.24%), intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM had significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE had lower efficacy than all other TA-TMA therapies exception to supportive care.