Ferric Carboxymaltose In Patients Research Articles

P075 What has parenteral iron got to do with rheumatology?

Abstract Background/Aims A 39 year-old female had been experiencing a six-month history of insidious onset migratory joint and bone pain, stiffness, malaise and over the last four months proximal muscle weakness. There had been partial relief with the use of non-steroidal anti-inflammatory medication. Past medical history included severe menorrhagia secondary to fibroids with a haemoglobin of 50g/dl on a handful of occasions, requiring x3 iron infusions (Ferric Carboxymaltose (FCM)1000mg) over a two year period. The last two infusions were provided three months apart. After each infusion, profound fatigue ensued. A blood test demonstrated an elevated ALP 301 (RR 30-130 U/L), reduced phosphate 0.48 (RR 0.8-1.5mmol/L) and mildly reduced 25OH vitamin D 44 (RR 50-140nmol/L). Corrected calcium was low-normal 2.29 (RR 2.2-2.6mmol/L) as was PTH 4.62 (RR 1.6-6.9pmol/L). A CTCAP excluded malignancy. Methods The patient had been treated with Cholecalciferol 1000iu and Dipyridamole 100mg daily with weekly blood test monitoring for six weeks prior to review in the metabolic bone clinic. Dipyridamole aided biochemical and symptomatic improvement. Further tests returned with an elevated FGF23 252 (RR 0-100 RU/ml), a normal Urine phosphate/Creatinine 1.6 and TmP/GFR ratio (suggesting the FGF23 effect on the kidney was not severe or its effects inhibited by Dipyridamole). ALP had reduced slightly to 269, PTH was elevated at 10.81 (RR 1.95-8.49micromol/L) and 1,25 Dihydroxy Vit D 182 (RR43-144 pmol/L). Results The patient was diagnosed with Parenteral iron triggered hypophosphatemia osteomalacia (6H-syndrome). A delayed diagnosis and referral resulted from unfamiliarity of side-effects of parenteral iron, especially Ferric Carboxymaltose, which has an alert on the GOV.UK website. The patient discontinued IV iron and was placed on oral Ferrous Gluconate 300mg daily. In retrospect, bone and joint pain was likely the result of enthesial pain and pseudofractures. In patients with diagnostic uncertainty, an isotope bone scan would be beneficial in assessing the extent of such pseudofractures. Hypophosphatemia is common following FCM (≥1/100 to < 1/10), and often self-limiting and asymptomatic. However, sustained hypophosphatemia (from recurrent infusions) can result in osteomalacia. Both anaemia and certain iron preparations can cause an elevation in FGF23 leading to increased urinary phosphate excretion. Dipyridamole has anti-phosphaturic effects by inhibiting FGF23. Conclusion It is advised in such patients to monitor serum phosphate levels at two- and five-weeks post infusion and to re-evaluate therapy with FCM in patients with persistent hypophosphatemia. It is common for symptoms, imaging, and biochemistry (FGF23 and ALP) to remain elevated/positive several months after diagnosis. This case highlights the need to ask about iron infusions in the drug history in patients presenting with hypophosphatemia and to be aware that musculoskeletal pain following iron infusions can be a sign of osteomalacia which will need investigating. Rarely, proximal muscle weakness can occur following the above iron preparation. Disclosure K.M. Achilleos: None. V. Rajagopal: None. C. Adams: None. G. Clunie: None.

Cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anemia in England

Aims Anemia is the most common extraintestinal complication of inflammatory bowel disease (IBD), with approximately half of cases caused by iron deficiency (ID). Intravenous iron is the preferred ID anemia (IDA) treatment where oral iron is contraindicated, ineffective or not tolerated, or where ID correction is urgent. The objective was to evaluate the cost-utility of ferric derisomaltose (FDI) versus ferric carboxymaltose (FCM) in patients with IBD and IDA in England, in whom IV iron treatment is preferred. Materials and methods A patient-level simulation model was developed, capturing quality of life (QoL) differences based on SF-36v2 data from the PHOSPHARE-IBD randomized controlled trial, monitoring and incidence of post-infusion hypophosphatemia, and number of iron infusions required. Analyses were conducted over a five-year time horizon from the Department of Health and Social Care (DHSC) perspective, with healthcare provider and societal perspectives adopted in separate analyses. Future costs and effects were discounted at 3.5% per annum and one-way and probabilistic sensitivity analyses were performed. Results FDI increased quality-adjusted life expectancy by 0.075 QALYs versus FCM from 2.57 QALYs to 2.65 QALYs per patient. Patients receiving FDI required 1.63 fewer iron infusions over the five-year time horizon, driving infusion-related cost savings of GBP 496 per patient (GBP 2,188 versus GBP 1,692) from the DHSC perspective. Costs of monitoring and treating hypophosphatemia after FCM were GBP 226, yielding total savings of GBP 722 per patient (GBP 2,414 versus GBP 1,692) over the five-year time horizon. FDI also led to reduced costs versus FCM in the societal and provider analyses and was therefore the dominant intervention across all three perspectives. Limitations The analysis did not capture patient adherence, hypophosphatemic osteomalacia, or fractures. Conclusions Results showed that FDI improved patient QoL and reduced direct healthcare expenditure versus FCM in patients with IBD and IDA in England.

P1050 A cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anaemia in Finland

Abstract Background Anaemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with iron deficiency being the most common cause. Iron deficiency anaemia (IDA) can be treated with oral iron, but where oral administration is contraindicated, not tolerated, or proves to be ineffective, intravenous (IV) iron is the preferred treatment option, facilitating rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are two high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), with FCM administration resulting in significantly higher hypophosphataemia incidence versus FDI, and phosphate monitoring after repeat FCM infusions is now recommended in the FCM product information (PI). Between 2000 and 2020, Finland has seen the average incidence of IBD increase by 2.4% annually, accompanied by a commensurate increase in sequelae such as IDA. The objective of the present study was therefore to evaluate the cost-utility of FDI versus FCM in patients with IBD and IDA in Finland. Methods A published patient-level simulation model was used to evaluate the cost-utility of FDI versus FCM in Finland. The model captured quality of life differences based on SF-36 data from the PHOSPHARE-IBD RCT and differences in the number of FDI and FCM infusions required. A Finnish societal perspective was adopted and the analysis was conducted over a five-year time horizon. Unit costs were obtained from publicly available Finnish sources. Costs were reported in 2022 Euros and a discount rate of 3% per annum was applied to future costs and effects. Results Over the five-year time horizon, patients received 3.95 courses of iron treatment on average, requiring 1.63 fewer infusions of FDI than FCM (5.57 versus 7.20). This resulted in iron procurement and administration cost savings of EUR 471 with FDI versus FCM (EUR 2,286 versus EUR 2,757). Differences in health-related quality of life and the number of IV iron infusions resulted in an increase of 0.076 quality-adjusted life years with FDI versus FCM. Further cost savings of EUR 273 over five years were also realised with FDI versus FCM, driven by reduced need for phosphate testing (saving EUR 90) and reduced travel and productivity loss (saving EUR 183). Total cost savings were EUR 745 (Figure) and FDI was therefore the dominant intervention. Conclusion Relative to FCM, FDI resulted in improvements in quality-adjusted life expectancy in Finnish patients with IBD and IDA. FDI also resulted in cost savings, arising from reduced infusion frequency, phosphate monitoring, patient travel, and productivity loss. FDI therefore represents the dominant choice of IV iron in Finnish patients with IBD and IDA.

Trends of phosphorus levels after intravenous administration of ferric carboxymaltose

Abstract Background Iron deficiency and anaemia are present in a large number of patients with heart failure. Intravenously ferric carboxymaltose (FCM) is the recommended treatment, but it may be associated with hypersensitivity reaction and hypophosphatemia, the later mainly in subjects with normal renal function. The prevalence of hypophosphatemia driven by FCM in patients with heart failure (HF) is not well established. Purpose To assess the prevalence and trends of serum phosphorus levels after FCM administration in outpatients with HF. Methods Prospective, observational, consecutive, and descriptive study of patients admitted in a HF clinic eligible to receive FCM between January 2022 and June 2022. Phosphorus and calcium homeostasis regulators (magnesium, vitamin D, parathyroid hormone, alkaline phosphatase) were drawn at baseline and after 3 weeks of the infusion. In those patients with documented hypophosphatemia after iron administration, a third measurement was performed at three months from baseline. Paired T-test was used to compare mean values and logistic regression to predict relationship of changes in serum phosphorus with other factors. Results 101 patients were included (71.5 ± 10.6 years, 31.7% women, LVEF 43.9 ±11.9%, 49.5% of ischaemic aetiology, glomerular filtration rate 39.44 ±10 mL/min/m2). Mean baseline phosphorous was 3.64 ± 0.66 mg/dL, declining to 2.74 ±0.88 mg/dL (p for trend = 0.001). Calcium, magnesium, and vitamin D also showed a post-infusion declining tendency (p = 0.001, p = 0.05 and p= 0.002, respectively), whereas PTH significantly increased (p = 0.015). At three weeks, 38 (37.6%) patients had phosphorous levels below the normal threshold (mean 2.15 ± 0.76 mg/dl), which normalized at three months from baseline (mean 3.12 ±0.77 mg/dl; p = 0.71) without specific treatment. Figure 1 shows phosphorus dynamics of the 38 patients with infusion hypophosphatemia. There was no predicted correlation between FCM dose, glomerular filtration rate and phosphorous trends (p = 0.627, P = 0.234 respectively). No clinical adverse event was reported. Conclusion Ferric carboxymaltose infusion in patients with HF is associated with a decline in circulating phosphorous, with 1 in 3 patients showing frank hypophosphatemia. This effect is transient and does not require treatment nor active phosphorus monitoring.Trends of hypophosphatemia

Association between sex and efficacy of intravenous ferric carboxymaltose in patients with acute heart failure and iron deficiency: an AFFIRM-AHF subgroup analysis

Abstract Background/Introduction Heart failure (HF) pathophysiology, clinical presentation and treatment response is known to differ between males and females (1). In the AFFIRM-AHF trial, intravenous (IV) ferric carboxymaltose (FCM) reduced the risk of HF hospitalisations and improved quality of life vs placebo in patients with iron deficiency who had stabilised following an acute HF (AHF) episode (2,3); the effect of sex on outcomes with iron-repletion therapy in these high-risk patients has not been fully explored. Purpose To investigate the interaction between sex and the effects of FCM vs placebo on clinical outcomes in the AFFIRM-AHF population. Methods In AFFIRM-AHF, patients with left ventricular ejection fraction <50% and iron deficiency (defined as serum ferritin <100 ng/mL, or 100–299 ng/mL if transferrin saturation is <20%) who had stabilised following recent hospitalisation for AHF were randomised 1:1 to receive IV FCM or placebo for up to 24 weeks.2 The primary endpoint was a composite of total HF hospitalisations and cardiovascular (CV) death up to Week 52; secondary endpoints are listed in the Figure.2 In this prespecified analysis, AFFIRM-AHF patients were stratified into male and female subgroups and the interaction between sex and clinical outcomes with FCM vs placebo was explored. Results Of the 1108 patients included in the AFFIRM-AHF full analysis set, 614 (FCM: 314; placebo: 300) were male and 494 (FCM: 244; placebo: 250) were female. At baseline, a New York Heart Association functional class of III and above was more common in females (59.0%) than in males (48.4%). For the primary endpoint, the adjusted annualised event rate per 100 patient-years with FCM vs placebo was 53.3 vs 83.3 in males (rate ratio [RR] 0.64; 95% confidence interval [CI] 0.46–0.89) and 63.1 vs 60.3 in females (RR 1.05; 95% CI 0.72–1.53) (Figure). For all secondary endpoints except time to CV death, effect sizes in male and female subgroups were similar to those for the primary endpoint. The interaction between sex and treatment effect was non-significant for the primary endpoint (P-interaction=0.054) but reached significance for the secondary endpoints of total CV hospitalisations and CV death (P-interaction=0.024) and time to first HF hospitalisation or CV death (P-interaction=0.043). Conclusion(s) The results of this exploratory subgroup analysis suggest that iron deficiency treatment with IV FCM following an AHF episode may be more effective in males than in females; this may be related to baseline differences between sex subgroups, beyond the factors adjusted for in this analysis.Figure

Incidence of Hypophosphatemia After Intravenous Administration of Iron: A Matching-Adjusted Indirect Comparison of Data from Japanese Randomized Controlled Trials.

Intravenous (IV) administration of iron is considered a safe and efficacious treatment for iron deficiency anemia (IDA), recommended in patients requiring rapid replenishment of iron, or intolerant or unresponsive to oral administration of iron. Recent randomized controlled trials (RCTs) have shown high incidence of hypophosphatemia after administration of two IV iron preparations: saccharated ferric oxide (SFO) and ferric carboxymaltose (FCM). The present study aimed to conduct matching-adjusted indirect comparison (MAIC) of hypophosphatemia incidence with these iron formulations and ferric derisomaltose (FDI) based on data from head-to-head RCTs conducted in Japan. A MAIC of hypophosphatemia incidence was conducted on the basis of data from two head-to-head RCTs. The relative odds of hypophosphatemia with FDI versus SFO were obtained from patient-level data from a recent RCT and adjusted for cumulative iron dose, while parametric models of serum phosphate levels from a separate RCT were used to estimate the relative odds of hypophosphatemia with FCM with SFO. An anchored MAIC was then conducted comparing FDI with FCM. The adjusted odds of experiencing hypophosphatemia were significantly lower with FDI than SFO [odds ratio (OR) of 0.02; 95%confidence interval(CI) 0.01-0.05]. The parametric models of serum phosphate from the RCT comparing FCM with SFO provided an estimated OR of 1.17 for the incidence of hypophosphatemia with FCM versus SFO. Combining the two estimates in the MAIC showed that the odds of experiencing hypophosphatemia would be 52.5 (95%CI 27.7-99.4) times higher with FCM than FDI in patients with IDA associated with heavy menstrual bleeding in Japan. Direct comparison of patient-level data and a MAIC from two RCTs in Japanese patients with heavy menstrual bleeding indicated that hypophosphatemia is less frequent in patients treated with FDI than those with FCM or SFO. Results are in agreement with RCTs comparing FDI and FCM in patients with various etiologies conducted in the USA and Europe.

Intravenous ferric carboxymaltose for iron repletion following acute heart failure in patients with and without diabetes: a subgroup analysis of the randomized AFFIRM-AHF trial.

In AFFIRM-AHF, treatment of iron deficiency with intravenous ferric carboxymaltose (FCM) reduced the risk of heart failure (HF) hospitalization and improved quality of life (QoL) vs placebo in patients stabilized following an acute HF (AHF) episode, with no effect on cardiovascular (CV) death. Diabetes and iron deficiency frequently accompany AHF. This post hoc analysis explored the effects of diabetes on outcomes in AFFIRM-AHF patients. Patients were stratified by diabetes yes/no at baseline. The effects of FCM vs placebo on primary (total HF hospitalizations and CV death) and secondary (total CV hospitalizations and CV death; CV death; total HF hospitalizations; time to first HF hospitalization or CV death; and days lost due to HF hospitalizations or CV death) endpoints at Week 52 and change vs baseline in disease-specific QoL (12-item Kansas City Cardiomyopathy Questionnaire [KCCQ-12]) at Week 24 were assessed by subgroup. For each endpoint, the interaction between diabetes status and treatment outcome was explored. Of 1108 AFFIRM-AHF patients, 475 (FCM: 231; placebo: 244) had diabetes and 633 (FCM:327; placebo: 306) did not have diabetes. Patients with diabetes were more commonly male (61.5% vs 50.9%), with a higher frequency of ischemic HF etiology (57.9% vs 39.0%), prior HF history (77.7% vs 66.5%), and comorbidities (including previous myocardial infarction [49.3% vs 32.9%] and chronic kidney disease [51.4% vs 32.4%]) than those without diabetes. The annualized event rate/100patient-years with FCM vs placebo for the primary endpoint was 66.9 vs 80.9 in patients with diabetes (rate ratio [RR]: 0.83, 95% CI 0.58-1.81) and 51.3 vs 66.9 in patients without diabetes (RR:0.77, 95% CI 0.55-1.07), with no significant interaction between diabetes status and treatment effect (pinteraction = 0.76). Similar findings were observed for secondary outcomes. Change from baseline in KCCQ-12 overall summary score was numerically greater with FCM vs placebo at almost all time points in both subgroups, with no interaction between diabetes and treatment effect at Week 24. The clinical and QoL benefits observed with intravenous FCM in patients with iron deficiency following stabilization from an AHF episode are independent of diabetes status. Trial registration Clinicaltrials.gov, NCT02937454 (registered 10.18.2016).

Ferric Carboxymaltose in Patients with Acute Decompensated Heart Failure and Iron Deficiency: A Real-Life Study.

Background: The correction of iron deficiency (ID) with ferric carboxymaltose (FCM) is a recommended intervention in heart failure (HF) with reduced ejection fraction. Our aim is to evaluate, in a real-life setting, the clinical significance of ID screening and FCM treatment in acute decompensated HF (ADHF). Methods: In a cohort of ADHF patients, the prevalence of ID and FCM administration were investigated. Among the 104 patients admitted for ADHF, in n = 90 (median age 84, 53.5% with preserved left ventricular ejection fraction-LVEF), a complete iron status evaluation was obtained. ID was detected in n = 73 (81.1%), 55 of whom were treated with in-hospital FCM. The target dose was reached in n = 13. Results: No significant differences were detected in terms of age, sex, comorbidities, or LVEF between the FCM-supplemented and -unsupplemented patients. During a median follow-up of 427 days (IQR 405-466) among the FCM-supplemented patients, only 14.5% received FCM after discharge; the mortality and rehospitalizations among FCM-supplemented and -unsupplemented patients were similar (p = ns). In a follow-up evaluation, ID was still present in 75.0% of the FCM-supplemented patients and in 69.2% of the unsupplemented patients (p = ns). Conclusions: In this real-life ADHF cohort, FCM was administered at lower-than-prescribed doses, thus having no impact on ID correction. The significance of our findings is that only achieving the target dose of FCM and pursuing outpatient treatment can correct ID and produce long-term clinical benefits.

Is the Benefit of Treating Iron Deficiency Greater in Acute Heart Failure with Renal Dysfunction?

This study aims to analyse whether in acute heart failure (AHF) with iron deficiency (ID), the administration of ferric carboxymaltose (FCM) produces a greater benefit in renal dysfunction. A total of 812 consecutive patients admitted for AHF and ID were studied. Untreated (n:272) and treated (n:540) patients were compared. The six-month prevalence of a combined event (readmission for HF, all-cause death, and emergency department visit for decompensation) was analysed. Three grades of renal dysfunction (KDIGO) were compared, Group 1 (grades 1 and 2), Group 2 (grades 3a and 3b), and Group 3 (grades 4 and 5). There were differences in sex distribution (untreated group: males 39.7% vs. treated group: males 51.9%; p < 0.001). Sex-adjusted combined event analysis showed a greater benefit in Group 1 (OR: 0.31, 95% CI:0.19-0.5; p < 0.001) and Group 2 (OR: 0.23, 95% CI:0.14-0.38; p < 0.001), but not in Group 3 (OR: 0.51, 95% CI:0.17-0.55; p: 0.237). The administration of FCM in patients with AHF and ID reduces the combined event analysed. The benefit is greater when renal dysfunction is present, except in very advanced degrees where no significant benefit is obtained.

Effect of Preoperative Administration of Intravenous Ferric Carboxymaltose in Patients with Iron Deficiency Anemia after Off-Pump Coronary Artery Bypass Grafting: A Randomized Controlled Trial.

Patients scheduled for cardiac surgery often have anemia and iron deficiency. We investigated the effect of the preoperative administration of intravenous ferric carboxymaltose (IVFC) in patients with iron deficiency anemia (IDA) who were due to undergo off-pump coronary artery bypass grafting (OPCAB). Patients who were due to undergo elective OPCAB between February 2019 and March 2022 who had IDA (n = 86) were included in this single center, randomized, parallel-group controlled study. The participants were randomly assigned (1:1) to receive either IVFC or placebo treatment. Postoperative hematologic parameters [hemoglobin (Hb), hematocrit, serum iron concentration, total iron-binding capacity, transferrin saturation, transferrin concentration, and ferritin concentration] and the changes in these parameters during the follow-up period were the primary and secondary outcomes, respectively. The tertiary endpoints were early clinical outcomes, such as the volume of mediastinal drainage and the need for blood transfusions. IVFC treatment significantly reduced the need for red blood cell (RBC) and platelet transfusions. Despite receiving fewer RBC transfusions, patients in the treatment group had higher levels of Hb, hematocrit, and serum iron and ferritin concentrations during weeks 1 and 12 after surgery. No serious adverse events occurred during the study period. Preoperative IVFC treatment in patients with IDA undergoing OPCAB improved the values of the hematologic parameters and iron bioavailability. Therefore, is a useful strategy for stabilizing patients prior to OPCAB.

EE254 A Cost-Utility Analysis of Ferric Derisomaltose Versus Ferric Carboxymaltose in Patients With Inflammatory Bowel Disease in Italy

Anemia is the most common extraintestinal complication of inflammatory bowel disease (IBD), with approximately half of cases caused by iron deficiency (ID). Intravenous (IV) iron is the preferred ID anemia (IDA) treatment where oral iron is contraindicated, ineffective or not tolerated, or where correction of ID is urgent. The recent PHOSPHARE-IBD randomized controlled trial (RCT; ClinialTrials.gov ID NCT03466983) reported significantly higher incidence of hypophosphatemia after treatment with ferric carboxymaltose (FCM) than ferric derisomaltose (FDI). The present study objective was to evaluate the cost-utility of FDI versus FCM in patients with IBD in Italy.

Impact of ischaemic aetiology on the efficacy of intravenous ferric carboxymaltose in patients with iron deficiency and acute heart failure: insights from the AFFIRM-AHF trial.

In AFFIRM-AHF, intravenous ferric carboxymaltose (FCM) reduced heart failure (HF) hospitalisations and improved quality of life versus placebo in iron-deficient patients stabilised after an acute HF episode. This analysis explored the effects of FCM versus placebo in patients with ischaemic and non-ischaemic HF aetiology. We included 1082 patients from AFFIRM-AHF: 590 with ischaemic HF (defined as investigator-reported ischaemic HF aetiology and/or prior acute myocardial infarction and/or prior coronary revascularisation) and 492 with non-ischaemic HF. The prevalences of male sex, comorbidities, and history of HF were higher in the ischaemic versus non-ischaemic HF subgroup. Annualised event rates for the primary composite outcome of total HF hospitalisations and cardiovascular death with FCM versus placebo were 65.3 versus 100.6 per 100 patient-years in the ischaemic HF subgroup (rate ratio [RR] 0.65, 95% confidence interval [CI] 0.47-0.89, p=0.007) and 58.3 versus 52.5 in the non-ischaemic HF subgroup (RR 1.11, 95% CI 0.75-1.66, p=0.60) (pinteraction =0.039). An interaction between HF aetiology and treatment effect was also observed for the secondary outcome of total HF hospitalisations (pinteraction =0.038). A nominal increase in quality of life, assessed using the 12-item Kansas City Cardiomyopathy Questionnaire, was observed with FCM versus placebo, within each subgroup. Heart failure hospitalisations and cardiovascular deaths occurred at a higher rate in patients with ishaemic versus those with non-ischaemic HF and were reduced by FCM versus placebo only in ischaemic patients. Further studies are needed to assess the role of aetiology in FCM efficacy.

Hypophosphataemia following ferric derisomaltose and ferric carboxymaltose in patients with iron deficiency anaemia due to inflammatory bowel disease (PHOSPHARE-IBD): a randomised clinical trial

ObjectiveIntravenous iron—a common treatment for anaemia and iron deficiency due to inflammatory bowel disease (IBD)—can cause hypophosphataemia. This trial compared the incidence of hypophosphataemia after treatment with ferric carboxymaltose (FCM)...

Erhalt von Leistungsfähigkeit und Lebensqualität bei chronischer Herzinsuffizienz (Teil 2)

This 3‑part article aims to treatment possibilities to review maintain mobility and quality of life in patients with heart failure, covering the aspects of guideline-conform drug therapy, treatment of comorbidities, and the influence of exercise training. This second part discusses that intravenous administration of ferric carboxymaltose in patients with iron deficiency can improve exercise capacity. Small studies have indicated that testosterone administration can be useful in highly selected patients with low muscle mass. Initial positive data are available for sodium-glucose Co-transporter 2 (SGLT2) inhibitors in patients with HFrEF and HFpEF. Interventional pulmonary vein isolation used to restore sinus rhythm in patients with atrial fibrillation and heart failure can have positive effects on exercise capacity. Treatment of other comorbidities of heart failure, such as sleep-disordered breathing, diabetes mellitus, chronic kidney disease, or depression, showed some improvements in exercise capacity and/or quality of life but the meaningfulness of the available data is limited.

PCR104 Improvements in Health Utility Scores after Administration of Ferric Derisomaltose Versus Ferric Carboxymaltose in Patients with Inflammatory Bowel Disease and Iron Deficiency Anemia

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that commonly result in iron deficiency anemia (IDA) due to impaired iron absorption and chronic blood loss. Patients with IBD experience reduced health-related quality of life, with fatigue playing a key role. The aim of the present analysis was to calculate health state utility values (HSUVs) from a recent randomized controlled trial (RCT) of intravenous iron in the treatment of patients with IBD and IDA.

Pharmacoeconomic analysis of ferric carboxymaltose in patients with chronic heart failure and iron deficiency in the Russian Federation

Aim: To evaluate the economic efficiency of using ferric carboxymaltose (FCM) in patients with chronic heart failure with reduced left ventricular ejection fraction (CHFrEF) and iron deficiency (ID) in the Russian Federation Methods: The analysis of the cost of maintaining CHFrEF with ID was carried out and an analytical decision-making model was built in MS Excel, which allows estimating the costs from the position of the state in the management of patients with CHFrEF with ID when using FCM in comparison with placebo. Results: The use of FCM in 633,301 patients with CHFrEF and ID for 1 year will prevent 72,386 hospitalizations for CHF and reduce the number of days spent by patients in the hospital by 1,136,141 days. Taking into account the direct costs of stopping adverse events, as well as the indirect costs of paying disability benefits and GDP losses, the potential economic benefit of using FCV when prescribing 633,301 CHFrEF and DJ to patients for 1 year can be 4.280 million rubles. per year of therapy. The use of FCM in patients with CHFrEF and ID is advisable immediately after an episode of CHF decompensation in order to reduce the risk of subsequent hospitalizations for worsening CHF and increase the cost per patient by only 4 642 rubles. per year (18 %), while significantly improving the prognosis of patients and their quality of life. Conclusion: FCM can be recommended for inclusion in the standards of medical care, clinical guidelines, formularies of healthcare facilities, application templates within the framework of the regional (RLO) and federal drug benefits, as well as federal and regional programs aimed at improving the control of the clinical course CHFrEF with ID.

Budget Impact of Intravenous Iron Therapy with Ferric Carboxymaltose in Patients with Chronic Heart Failure with Reduced Ejection Fraction (HFrEF) and Iron Deficiency in Switzerland.

AimsA budget impact analysis compared treating patients with heart failure (HF) and reduced ejection fraction (HFrEF) and iron deficiency (ID) in Switzerland with intravenous ferric carboxymaltose (FCM) or placebo.MethodsClinical data from four international randomized trials showed that FCM versus placebo treatment was associated with a reduced hospitalization rate due to HF. The budget impact of this was modelled over 1 year. Hospital treatment costs for HFrEF, FCM drug costs, and estimated patient numbers were based on published data, official tariffs, specially commissioned analyses of SwissDRG data, and clinical and diagnosis-related groups (DRG) coding expert opinion. The original cost year was 2015. Sensitivity analyses were conducted including updated unit costs from 2019/2020.ResultsFCM treatment was associated with average cost savings of Swiss Francs (SFr) 503 per patient per year from the perspective of the Swiss mandatory health insurance system. Extrapolating across all eligible HFrEF patients with ID in Switzerland, this amounted to estimated savings of SFr 23,336,873. Sensitivity analyses showed these results to be robust in the face of changes to input parameters like treatment costs, different hospital settings, updated unit costs, and including outpatient treatment and patient co-payments in the analysis.ConclusionsThe present analysis shows that using FCM to treat HFrEF patients with ID in line with current guideline recommendations resulted not only in medical benefits but also in significant cost savings. The analysis also provides an example of the pitfalls of transferring economic evaluation results, even between countries with similar hospital reimbursement systems.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-022-00341-7.

Sample size estimation for recurrent event data using multifrailty and multilevel survival models

In epidemiology and clinical research, recurrent events refer to individuals who are likely to experience transient clinical events repeatedly over an observation period. Examples include hospitalizations in patients with heart failure, fractures in osteoporosis studies and the occurrence of new lesions in oncology. We provided an in-depth analysis of the sample size required for the analysis of recurrent time-to-event data using multifrailty or multilevel survival models. We covered the topic from the simple shared frailty model to a hierarchical or joint modeling. We relied on a Wald-type test statistic to estimate the sample size assuming either a single or multiple endpoints. The simulations revealed that power decreased as heterogeneity increased. We also observed that it was preferable to maximize the number of patients (rather than the number of events per patient) as power increased with the number of patients for a fixed number of events. Each model investigated can address the question of the number of subjects for recurrent events. However, depending on the research question, one model will be more suitable than another. We illustrated our methodology with the AFFIRM-AHF trial investigating the effect of intravenous ferric carboxymaltose in patients hospitalised for acute heart failure. Sample size; Frailty model; Recurrent events; Randomized; Joint models Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts.

Responder analysis for improvement in 6-min walk test with ferric carboxymaltose in patients with heart failure with reduced ejection fraction and iron deficiency.

AimImproving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR‐HF and CONFIRM‐HF assessed the likelihood of improvement or deterioration in 6‐min walk test (6MWT) among iron‐deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM).Methods and resultsData for 760 patients (FCM: n = 454; placebo: n = 306) were analysed. The proportions of patients receiving FCM or placebo who had ≥20, ≥30, and ≥40 m improvements or ≥10 m deterioration in 6MWT at 12 and 24 weeks were assessed. Patients receiving FCM experienced a mean (standard deviation) 31.1 (62.3) m improvement in 6MWT versus 0.1 (77.1) m improvement for placebo at week 12 (difference in mean changes 26.8 [16.6–37.0]). At week 12, the odds [95% confidence interval] of 6MWT improvements of ≥20 m (odds ratio 2.16 [1.57–2.96]; p < 0.0001), ≥30 m (2.00 [1.44–2.78]; p < 0.0001), and ≥40 m (2.29 [1.60–3.27]; p < 0.0001) were greater with FCM versus placebo, while the odds of a deterioration ≥10 m were reduced with FCM versus placebo (0.55 [0.38–0.80]; p = 0.0019). Among patients who experienced 6MWT improvements of ≥20, ≥30, or ≥40 m with FCM at week 12, more than 80% sustained this improvement at week 24.ConclusionFerric carboxymaltose resulted in a significantly higher likelihood of improvement and a reduced likelihood of deterioration in 6MWT versus placebo among iron‐deficient patients with HF. Of the patients experiencing clinically significant improvements at week 12, the majority sustained this improvement at week 24. These results are supportive of FCM to improve exercise capacity in HF.

Short‐Term Changes in Left and Right Ventricular Cardiac Magnetic Resonance Feature Tracking Strain Following Ferric Carboxymaltose in Patients With Heart Failure: A Substudy of the Myocardial‐IRON Trial

BackgroundThe mechanisms explaining the clinical benefits of ferric carboximaltose (FCM) in patients with heart failure, reduced or intermediate left ventricular ejection fraction, and iron deficiency remain not fully clarified. The Myocardial‐IRON trial showed short‐term cardiac magnetic resonance (CMR) changes suggesting myocardial iron repletion following administration of FCM but failed to find a significant increase in left ventricular ejection fraction in the whole sample. Conversely, the strain assessment could evaluate more specifically subtle changes in contractility. In this subanalysis, we aimed to evaluate the effect of FCM on the short‐term left and right ventricular CMR feature tracking derived strain.Methods and ResultsThis is a post hoc subanalysis of the double‐blind, placebo‐controlled, randomized clinical trial that enrolled 53 ambulatory patients with heart failure and left ventricular ejection fraction <50%, and iron deficiency [Myocardial‐IRON trial (NCT03398681)]. Three‐dimensional left and 2‐dimensional right ventricular CMR tracking strain (longitudinal, circumferential, and radial) changes were evaluated before, 7 and 30 days after randomization using linear mixed‐effect analysis. The median (interquartile range) age of the sample was 73 years (65–78), and 40 (75.5%) were men. At baseline, there were no significant differences in CMR feature tracking strain parameters across both treatment arms. At 7 days, the only global 3‐dimensional left ventricular circumferential strain was significantly higher in the FCM treatment‐arm (difference: −1.6%, P=0.001). At 30 days, and compared with placebo, global 3‐dimensional left ventricular strain parameters significantly improved in those allocated to FCM treatment‐arm [longitudinal (difference: −2.3%, P<0.001), circumferential (difference: −2.5%, P<0.001), and radial (difference: 4.2%, P=0.002)]. Likewise, significant improvements in global right ventricular strain parameters were found in the active arm at 30 days (longitudinal [difference: −3.3%, P=0.010], circumferential [difference: −4.5%, P<0.001], and radial [difference: 4.5%, P=0.027]).ConclusionsIn patients with stable heart failure, left ventricular ejection fraction <50%, and iron deficiency, treatment with FCM was associated with short‐term improvements in left and right ventricular function assessed by CMR feature tracking derived strain parameters.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03398681.