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Research Article
3 October 2019

Ferric carboxymaltose for patients with heart failure and iron deficiency in Italy: cost–effectiveness and budget impact

Abstract

Aim: To evaluate the cost–effectiveness of intravenous ferric carboxymaltose (FCM) versus placebo for the management of iron deficiency in patients with chronic heart failure in the Italian healthcare system and to estimate its impact on the national healthcare budget. Materials & methods: A Markov model was developed to project costs and health outcomes over 1 year, based on data from literature. Healthcare resources consumption was derived from an e-survey administered to clinicians. Costs were obtained from official tariffs. Results: Treatment with FCM represents a dominant strategy compared with placebo, leading to national budget annual savings of 20–97 million Euros, according to different increasing utilization rates. Conclusion: FCM is a cost-saving option for the treatment of chronic heart failure patients with iron deficiency in Italy.
Heart failure (HF) is recognized as an alteration of the heart structure that leads to insufficient cardiac function. As a consequence, organs and tissues receive insufficient oxygen to meet their metabolic needs. The reaction of the organism to insufficient function of the heart leads to an accumulation of sodium and water in the lungs and tissues. Symptoms include shortness of breath, reduced exercise tolerance, fatigue, edema. The condition may deteriorate until it leads to acute pulmonary edema and death.
Approximately 600,000 people currently suffer from HF in Italy and it is estimated that its frequency doubles for every decade of age (after the age of 65 it reaches about 10%) [1]. HF in patients aged over 65 years is the most common cause of hospitalization and it accounts for about 5% of all urgent hospital access [2]. For these reasons, HF is considered a major public health problem.
Despite optimal conventional therapy, many patients with chronic heart failure (CHF) are subject to high rates of hospitalization and mortality [2–4]. About 50% of patients with CHF suffer from iron deficiency (ID), more pronounced symptoms, a higher risk of hospitalization and a lower quality of life [5–10].
Few randomized controlled trials (RCTs) comparing ferric carboxymaltose (FCM) with placebo have shown a clinical benefit after correcting ID in patients with CHF [8,11–13]. Following these observations, the European Society of Cardiology Heart Failure 2016 guidelines specifically recommended considering FCM for the treatment of ID in patients with HF [14]. This treatment may improve patients’ clinical conditions, helping to reduce future hospitalizations, duration of hospital stay and increase their quality of life.
The aim of the present study was to develop knowledge on the clinical and economic implications that can support stakeholders at the national level in the overall assessment of choices regarding the management of patients with HF and ID. In particular, the main aim of the study was to perform a cost–effectiveness analysis (CEA) comparing FCM to placebo in CHF patients, from the Italian Healthcare System perspective. The secondary objective of this analysis was to assess the impact on the budget of the Italian Healthcare System of the appropriate diffusion of a screening strategy for patients with HF, in order to identify cases of ID with subsequent treatment with FCM.

Materials & methods

A CEA model was developed with TreeAge Pro Software (TreeAge Software, Inc., MA, USA) based on data related to a budget impact model published by Theidel and colleagues [15]. This model was developed to project lifetime health (life years and quality-adjusted life years [QALYs]) and economic outcomes associated with FCM and placebo in the population considered. The model was implemented from pooled patient level data from the main RCTs comparing FCM with placebo [8,11–13]. The health states in the implemented model include New York Heart Association (NYHA) classes from I to IV. As described previously [15], data derived from clinical trials were used to develop a model for the prediction of hospitalization rates for CHF and NYHA class distribution over the time horizon of 52 weeks. A 1-week Markov cycle length was chosen for baseline analysis. The model structure is presented in Figure 1.
Figure 1. Schematic representation of the general model structure.
Patients start the process in NYHA classes II (33%) and III (67%).
NYHA: New York Heart Association.
Patients begin the process in NYHA classes II (33%) and III (67%) and subsequently move among the different NYHA classes in order to reproduce the distribution over time, as reported in Table 1. The model focuses on hospitalizations, exams and visits for CHF or related to CHF which are likely to be influenced by the NYHA classes. On the contrary, the rates of other types of events not related to the disease under consideration are assumed equal for the two cohorts and are excluded from the model. This assumption is also supported by the study by Anker and colleagues [16], which reported not statistically different rates of hospitalizations for all causes between the two populations (p = 0.056).
Table 1. Patient distribution over time according to different NYHA classes.
 Placebo (%)FCM (%)
NYHA classIIIIIIIVDeathIIIIIIIVDeath
Baseline03367000336700
Week 40.130.165.640.20.951.6461.40.1
Week 120.435.957.24.22.25.155.936.41.31.3
Week 240.543.345.86.34.15.463.127.31.92.3
Week 360.741.145.16.66.55.863.225.223.8
Week 520.939.244.26.98.96.163.123.52.15.2
FCM: Ferric carboxymaltose; NYHA: New York Heart Association.
The aim of this study was to assess the cost–effectiveness of FCM compared with placebo, taking into account improvement in NYHA class and the decrease in related consumption of healthcare resources. A secondary objective was to estimate the expected changes in the expenditure for the Italian Healthcare Service in the hypothesis of an increased diffusion of FCM utilization in patients with CHF and ID.
The analyses were conducted in accordance with the Consolidated Health Economic Evaluation Reporting Standards Statement [17] and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles of Good Practice for Budget Impact Analysis [18]. The Consolidated Health Economic Evaluation Reporting Standards checklist is reported in the Supplementary Material.

Healthcare resource consumption & costs

This analysis was performed from the Italian Healthcare System perspective. In the model, only direct healthcare resource consumption (direct costs) was included.
The collection of data on the consumption of healthcare resources for the different NYHA classes was undertaken by administering an ad hoc developed e-survey to clinicians in five Italian hospitals. A Delphi approach was applied since experts were asked to answer the questionnaire independently [19]. The questionnaire was made available to complete from 3 October 2018 to 20 December 2018. The choice of the hospitals focused on Lombardy region, since this is the region with the highest number of outpatient services with expertise in the management of CHF patients in the clinical practice [20]. Clinicians were asked to refer to the typical cohort of patients with CHF and to report data on healthcare resource utilization according to the four NYHA classes based on their clinical experience.
The questionnaire was organized into different sections for the collection of the following data categories: hospitalizations for reasons related to CHF (e.g., kidney failure, atrial fibrillation, etc.), rehabilitative admissions, outpatient rehabilitation services, specialist medical visits, general practitioner visits, laboratory exams/imaging and pharmacological therapy. Clinicians were required to indicate for each outpatient service (e.g., specialist visit, general practitioner visit, laboratory exam, etc.), the percentage of patients involved and the mean number per year; the same was applied for hospital admissions. Regarding medication, the questionnaire investigated different treatments for CHF according to guidelines [14]: angiotensin-converting enzyme inhibitors, sartans, β-blockers, spironolactone, digoxin, sacubitril–valsartan, ivabradine and diuretics. For each treatment, clinicians were asked to report the percentage of treated patients, distinguishing the patients at target dose, with dose taken above 50% and below 100% and with a dose taken below 50% of the target dose.
At last, for each cost category, a weighted mean was calculated on the basis of the number of responders.
With regard to hospitalizations for CHF, the weekly rate for FCM (0.0010) and for placebo (0.0026) were obtained from [15], which calculated them starting from pooled data based on the four trials [8,11–13]. These values are in line with those obtainable from the data reported by Anker and colleagues in another pooled analysis [16] performed on the same trials, which highlighted the statistically significant difference between FCM and placebo (p = 0.003).
The monetary quantification (2018, Eur) of the consumption of healthcare resources for the management of patients in the different NYHA classes was performed through diagnosis-related group reimbursement rates for hospitalizations, regional tariff values for outpatient services and drug prices. Concerning drugs, we performed a search on the Italian Pharmaceutical Database [21] that reports cost data for the National Healthcare Service.

Literature review & quality of life estimates

A systematic literature review was performed in May 2018 in order to retrieve the utility coefficients for patients with CHF for the different NYHA classes. The search strategy is reported in the Supplementary Material.

Cost–effectiveness analyses

Both incremental cost–effectiveness ratio (ICER) and incremental cost–utility ratio of FCM versus placebo were calculated by dividing the incremental cost by the incremental health improvement. Health outcomes and costs were not discounted, considering the short time horizon used in the analysis. Costs, utilities and rates were entered into the model along with a distribution: β for utilities, log-normal for rates and γ for costs.
Univariate analyses were performed according to the model parameters. In order to take into account parameters variability, second-order Monte Carlo simulations (10,000 iterations) were performed. The resulting scatterplot was plotted in the cost–effectiveness plane.

Budget impact analysis

Starting from the CEA model, a budget impact analysis (BIA) model was developed to estimate the expected changes in the expenditure for the Italian Healthcare Service in the hypothesis of an increased diffusion of FCM utilization in patients with CHF and ID.
In order to perform the BIA, a research of epidemiological data was performed focusing on CHF patients with ID. Considering that the prevalence of CHF in Italy is 1.25% [22], that 78.8% of CHF patients belong to NYHA classes II and III [23] and that 42.5% of these patients present ID [24], the total number of prevalent CHF patients with ID in Italy was estimated to be 253,201. The current patients’ distribution between the two strategies, FCM and placebo, was estimated by clinicians as 5 and 95%, respectively.
A BIA was performed considering different scenarios of increased utilization rates of FCM for patients with CHF and ID (25, 50 and 100%) over placebo.

Results

Healthcare resource consumption & costs

Five clinicians were involved in the study and all completed the e-survey. The estimated healthcare resource utilization is reported in Supplementary Table 1, while unit costs are summarized in Table 2. With regard to pharmacological treatment, we considered recommended daily doses according to 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic HF [14].
Table 2. Costs used in the model.
Cost itemValueCodeRef.
Hospitalizations:
– Hospital admission for CHF€3052DRG 127National DRG reimbursement
– Hospital admission for atrial fibrillation€2375DRG 138National DRG reimbursement
– Hospital admission for atherosclerosis€990DRG 133National DRG reimbursement
– Hospital admission for renal failure€3734DRG 316National DRG reimbursement
– Rehabilitation hospital admission€2870DRG 463National DRG reimbursement
Outpatient services:
– Outpatient rehabilitation services (1 cycle)€19.1193.36National Healthcare Service price list
– Cardiological visit€16.0189.01.3National Healthcare Service price list
– Other specialist visits (e.g., nephrologist)€17.9089.01.BNational Healthcare Service price list
– GP visit€15.19 [25] uplifted to 2018
– GP home visit€29.12 [25] uplifted to 2018
– Iron infusion€9.7199.23National Healthcare Service price list
Lab exams/imaging:
Liver function evaluation:
– ALT
– ALP
– AST
– Bilirubin
– Albumin
– Proteins
– γ-glutamyl transferase
– LDH
– Prothrombin time

€1.00
€1.04
€1.04
€1.13
€1.42
€1.13
€1.13
€1.13
€2.85

90.04.5
90.23.5
90.09.2
90.10.4
90.05.1
90.38.5
90.25.5
90.29.2
90.75.4

National Healthcare Service price list
Kidney function evaluation:
– Azotemia
– Creatinine
– Sodium
– Potassium

€1.13
€1.13
€1.02
€1.02

90.44.1
90.16.3
90.40.4
90.37.4
National Healthcare Service price list
Blood cell count€3.1790.62.2National Healthcare Service price list
Natriuretic peptide€24.6890.21.2National Healthcare Service price list
Potassium€1.0290.37.4National Healthcare Service price list
Lipid evaluation:
– Total cholesterol
– Cholesterol HDL
– Cholesterol LDL
– Triglycerides

€1.04
€1.43
€0.67
€1.17

90.14.3
90.14.1
90.13.C
90.43.2
National Healthcare Service price list
Urine examination€2.1790.44.3National Healthcare Service price list
Uric acid€1.1390.43.5National Healthcare Service price list
Thyroid-stimulating hormone€5.4690.42.1National Healthcare Service price list
Magnesium€1.5590.32.5National Healthcare Service price list
Electrocardiogram€11.6289.52National Healthcare Service price list
Echocardiogram€51.6588.72.1National Healthcare Service price list
Stress test€55.7889.41National Healthcare Service price list
Stress test (including assessment of oxygen consumption)€83.6789.44.1National Healthcare Service price list
Dynamic electrocardiogram (Holter)€61.9789.50National Healthcare Service price list
Magnetic resonance imaging heart€120.0888.92.3National Healthcare Service price list
Coronarography€1142DRG 125 (Day-Hospital)National DRG reimbursement
Drugs:
FCM (100 mg, 2 ml)€7.752 Public price according to ‘Determinazione Dirigenziale N. 0666–17, 12/12/2017’ (available from http://www.ao.lodi.it)
ACE-inhibitors (Ramipril 10 mg die)€0.31/day [21]
Sartans (Valsartan 320 mg die)€0.51/day [21]
β-blockers (Nebivolol 10 mg die)€0.44/day [21]
Spironolactone (50 mg die)€0.35/day [21]
Digossin (0.1875 mg die)€0.20/day [21]
Sacubitril-valsartan (1 cp 97 mg/103 mg bid)€6.85/day [21]
Ivabradine (15 mg die)€0.71/day [21]
Furosemide (25 mg)€0.05/day [21]
ACE: Angiotensin-converting enzyme; CHF: Chronic heart failure; DRG: Diagnosis-related group; FCM: Ferric carboxymaltose; GP: General practitioner; HDL: High-density lipoprotein; LDL: Low-density lipoprotein.
Weekly costs related to the healthcare resource consumption for the different NYHA classes are reported in Table 3. The weekly cost for hospital admission for CHF was calculated by multiplying the weekly rate for FCM and placebo (not distinguished by NYHA class as reported by the reference trial [15]) by the Hospital admission cost for CHF. The cost difference of about €5 is due to the lower weekly rate of hospitalization for FCM. For the other cost components reported in Table 3, weekly costs have been calculated by multiplying the weekly healthcare resource consumption by the corresponding unit costs. In general, higher CHF severity corresponded to higher costs.
Table 3. Cost components for the different NYHA classes.
Cost componentWeekly cost NYHA IWeekly cost NYHA IIWeekly cost NYHA IIIWeekly cost NYHA IV
Hospital admission for CHF
– FCM
– Placebo

€3.14
€8.00
Other hospital admissions€8.58€24.86€31.56€61.16
Visits/exams and other outpatient services€6.10€9.64€14.13€16.50
Drugs€7.00€18.74€28.37€14.64
CHF: Chronic heart failure; FCM: Ferric carboxymaltose; NYHA: New York Heart Association.

Literature review & quality of life estimates

The literature search (see Supplementary Material) yielded a total of six studies reporting utility coefficient values for at least one NYHA class. A summary of retrieved studies and related utility values is reported in Table 4.
Table 4. Summary of studies and utility values.
StudyPopulationNumber of patientsNYHA INYHA IINYHA IIINYHA IV
[26]Patients at least 18 years of age, with evidence of heart failure for at least 6 weeks, and in NYHA class III or IV8130.610.44
[27]Patients belonging to NYHA classes from I to IV640.934 (SD: 0.089)0.782 (SD: 0.244)0.553 (SD: 0.361)0.371 (SD: 0.407)
[28]Patients with moderate to severe heart failure and left ventricular systolic dysfunction53130.820.740.640.46
[29]Patients with CHF after acute myocardial infarction13950.855
(95% CI: 0.845–0.865)
0.771
(95% CI: 0.761–0.781)
0.673
(95% CI: 0.665–0.69)
0.532
(95% CI: 0.48–0.584)
[30]Patients with advanced heart failure990.970.80.650.3
[31]Subjects with documented systolic HF or diastolic HF10690.750.660.610.61
CHF: Chronic heart failure; HF: Heart failure; NYHA: New York Heart Association; SD: Standard deviation.
A meta-analysis (Stata software, metaan command) was performed in order to obtain utility coefficients for all NYHA classes (Table 5). Meta-analysis was only possible to perform for studies reporting confidence intervals or standard deviation estimates associated to the reported utility weights [27,29].
Table 5. Meta-analysis of utility coefficients for the different NYHA classes.
NYHA classUtility coefficient (95% CI)
I0.89 (0.82−0.97)
II0.77 (0.76−0.78)
III0.62 (0.50−0.74)
IV0.46 (0.30−0.61)
NYHA: New York Heart Association.

Cost–utility results

In the baseline scenario, the model estimated a mean cost per patient undergoing FCM of €3296 and a cost of €3699 for untreated patient. With regard to health outcomes, over the time horizon of 1 year, the model estimated an average life expectancy of 0.974 (0.703 QALYs) and 0.956 (0.642 QALYs) years for patients administered FCM and for those not treated with FCM, respectively. Treatment with FCM was associated with lower cost and higher life expectancy and QALYs, therefore emerging as a dominant strategy compared with patients with CHF and ID not receiving treatment.
Several one-way sensitivity analyses were performed on the main model parameters. Variations of ±50% in weekly costs for visits/exams, other hospital admissions and other outpatient services for the different NYHA classes were considered. Variations in the weekly cost of hospitalizations for CHF were estimated by varying the weekly hospitalization rates from 0.001 to 0.01, as reported in Table 6. The analyses revealed that the weekly rate of hospitalization for CHF (for FCM strategy) is the parameter which mainly influences variations in ICER. On the other hand, the variations on weekly costs for the different NYHA classes and rate of hospitalization for CHF for placebo strategy always reported the dominance of FCM (data not shown).
Table 6. One-way sensitivity analyses performed on the main model parameters.
Parameter variationICUR (FCM vs placebo)Δ cost (FCM vs placebo)Δ QALYs (FCM vs placebo)
Baseline scenarioFCM dominant-€4030.061
Time horizon (weeks):
– 24FCM dominant-€1040.023
– 28FCM dominant-€1470.027
– 32FCM dominant-€1910.033
– 36FCM dominant-€2340.038
– 40FCM dominant-€2760.043
– 44FCM dominant-€3190.049
– 48FCM dominant-€3620.054
– 52FCM dominant-€4030.061
Total FCM dose (mg):
– 1679FCM dominant-€4030.061
– 1761FCM dominant-€3970.061
– 1843FCM dominant-€3900.061
– 1925FCM dominant-€3840.061
– 2007FCM dominant-€3770.061
– 2090FCM dominant-€3710.061
– 2172FCM dominant-€3650.061
– 2254FCM dominant-€3580.061
– 2336FCM dominant-€3520.061
– 2418FCM dominant-€3460.061
– 2500FCM dominant-€3390.061
Weekly rate of hospitalization for CHF (FCM):
– 0.001FCM dominant-€4030.061
– 0.002FCM dominant-€2480.061
– 0.003FCM dominant-€940.061
– 0.004€993€610.061
– 0.005€3543€2150.061
– 0.006€6092€3700.061
– 0.007€8642€5240.061
– 0.008€11,191€6790.061
– 0.009€13,741€8330.061
– 0.01€16,290€9880.061
CHF: Chronic heart failure; FCM: Ferric carboxymaltose; ICUR: Incremental cost–utility ratio; QALY: Quality-adjusted life year.
A probabilistic sensitivity analysis has been performed according to variations in parameters summarized in Supplementary Table 2. The scatterplot of incremental costs versus incremental QALYs obtained from the Monte Carlo simulations is reported in Figure 2 applying a cost–effectiveness threshold of €20,000/QALY; the totality of points lies below this line, highlighting that FCM leads to better QALYs at lower costs.
Figure 2. Scatterplot of incremental costs versus incremental quality-adjusted life years obtained from Monte Carlo simulations for the comparison ferric carboxymaltose versus placebo.
QALY: Quality-adjusted life year.

BIA results

Considering a total of 253,201 prevalent CHF patients with ID in Italy, the current national annual budget impact was estimated to be €931,488,616. The adoption of enlarged screening for ID patients in this setting, leading to FCM utilization rates of 25, 50 and 100%, may result in a decrease in the total national budget of €20,408,003, €45,918,007 and €96,938,015, respectively (Table 7).
Table 7. Budget impact analysis.
 Current scenarioAlternative scenario 25%Alternative scenario 50%Alternative scenario 100%
 Percentage of patientsNumber of patientsTotal costPercentage of patientsNumber of patientsTotal costPercentage of patientsNumber of patientsTotal costPercentage of patientsNumber of patientsTotal cost
Ferinject5%12,660€41,727,53025%63,300€208,637,65050%126,601€417,275,301100%253,201€834,550,601
No treatment95%240,541€889,761,08675%189,901€702,442,96350%126,601€468,295,3090%0€0
Total budget impact  €931,488,616  €911,080,613  €885,570,609  €834,550,601
Savings in comparison to current scenario     -€20,408,003  -€45,918,007  -€96,938,015

Discussion

HF is defined as a global pandemic, affecting 26 million people worldwide [32]. ID is a common comorbidity for patients with CHF, affecting approximately 50% of them [5]. ID is also associated with increased disease severity and is a strong and independent predictor of outcome [5].
Recently, several studies have shown that ID correction through the supplementation of intravenous iron in this kind of patients could improve functional status and quality of life [8,11–13]. The present study aimed to perform a CEA and BIA in order to support decision makers in assessing the value of intravenous iron therapy for ID in CHF patients in Italian clinical practice.
The CEA model development relied on clinical data from RCTs and on healthcare resource consumption mainly derived from clinical practice. Considering a time horizon of one year, intravenous therapy with FCM resulted in a cost-saving strategy compared with placebo for the treatment of CHF patients with ID in Italy. Probabilistic sensitivity analyses showed the robustness of the CEA model: all simulations reported the cost-saving of FCM over placebo.
The CEA model showed that for Italy, FCM has a better cost–effectiveness profile than placebo compared with few other published studies undertaken in Europe. In particular, a study conducted in the UK [9] developed a CEA model based on the FAIR-HF trial from the National Health Service perspective with a time horizon of 24 weeks. The ICER of FCM compared with placebo was found to be €4414 per QALY gained, highlighting the cost–effectiveness of FCM. Another study conducted in Spain [33] and based on the same UK model showed that FCM treatment in patients with CHF and ID is cost effective with a cost per QALY gained of €6123.78, compared with no ID treatment. Similar results were observed by a study conducted in Sweden applying the same model [34]. They reported an ICER of €8194 per QALY for FCM compared with placebo. These CEA models provide insight into the cost–effectiveness of FCM compared with placebo but these studies are also limited by the short time horizon used for the analyses of only 24 weeks. Furthermore, these studies consider clinical data only from the FAIR-HF RCT, which involved 459 patients.
The results of the present study are confirmed by a recent cost–utility analysis conducted in four Nordic countries (Denmark, Finland, Norway and Sweden) by Hofmarcher and colleagues [35] with a time horizon of one year based on clinical data from CONFIRM-HF study. The authors reported for FCM higher QALYs (increase of 0.050 QALYs per patient) and lower costs (reductions from €36 to €484 per patient).
For the development of the CEA model for Italy, we relied on the study by [15] in the German setting which reported the results of a BIA model based on clinical outcomes from 833 patients participating in four different clinical trials. This approach allowed us to improve data robustness and to use the longer time horizon (52 weeks). Moreover, the lower cost applied in Italy for FCM compared with other European countries further highlights FCM dominance compared with no treatment.
Our model was implemented in order to perform a CEA but was also extended to perform a BIA in the Italian context. The BIA showed that it is possible to save from 20 to about 97 million Euros per year according to increased utilization rates of FCM of 25, 50 and 100% over no treatment in CHF patients with ID. As a consequence of the dominance of FCM over placebo, the results also show a saving profile of the use of FCM in Italian clinical practice. Of course, in countries where the cost of FCM is much higher than in Italy (e.g., USA), the cost benefit may be lost.
The present study has a number of limitations. First of all, the model results are greatly influenced by patients’ distribution among the different NYHA classes derived from RCT data for FCM and placebo, therefore the generalizability to a broader real-world setting should be performed with caution.
Another limitation refers to the costs for hospitalizations for CHF; although the reference trial [15] reported accurate hospitalization rates for the two alternatives considered, the study did not report hospitalization rates distinguished by NYHA class, and a more precise analysis could not be performed.
Third, we relied on clinical experts’ opinions through a Delphi approach in order to inform healthcare resource utilization for the model. Key opinion leaders were based in the Lombardy Region and may not necessarily represent the entire clinical community for other regions. A positive aspect worth noting is the fact that the consumption of healthcare resources was presented in natural units, as suggested by EUnetHTA guidelines [36], this will facilitate cost adjustment for other regions or countries.
As with other intravenous irons, treatment with FCM can be associated with decreased levels of phosphorus in the blood, also known as hypophosphataemia, which could affect even 40% of patients or more [37]. Hypophosphataemia is a well-documented adverse drug reaction stated in the EU Ferinject Summary of Product Characteristics. Incidental cases of hypophosphataemia requiring medical attention were reported mainly in patients with existing risk factors and after prolonged exposure to high-dose intravenous iron. However, most instances are transient and are not associated with clinical signs or symptoms, therefore the management of these events has been excluded from the present analysis.
Despite these limitations, this study provides an estimate of the potential savings from increased utilization rates of intravenous FCM for the treatment of patients with ID in Italy. Data emerging from observational studies or registries in the future will provide further evidence to strengthen models in order to obtain more accurate results.

Future perspective

In HF, ID is linked to disease severity and is recognized as a marker of poor prognosis, independent of other prognostic factors. Based on the evidence derived from trials investigating the use of FCM, the European Society of Cardiology guidelines for the management of HF patients made a specific recommendation that this iron formulation should be considered in symptomatic patients to alleviate HF symptoms and improve exercise capacity and quality of life. Ongoing and future studies will be able to confirm whether other third generation iron formulations have a similar impact on patients’ health.
Summary points
Chronic heart failure (CHF) is recognized as an alteration of the heart structure that leads to insufficient cardiac function. About 50% of patients with CHF suffer from iron deficiency (ID), more pronounced symptoms, a higher risk of hospitalization and a lower quality of life.
Few randomized controlled trials comparing ferric carboxymaltose (FCM) with placebo have shown a clinical benefit after correcting ID in patients with CHF.
In this study we performed a cost–effectiveness analysis comparing FCM to placebo in CHF patients with ID from the Italian Healthcare System perspective. Moreover, a budget impact analysis was undertaken considering different scenarios of increased utilization rates of FCM for patients with CHF and ID (25, 50 and 100%) over placebo.
A Markov model was developed to project costs and health outcomes associated to the considered strategies. Clinical data and data on patients’ quality of life were derived from published literature, while data on the consumption of healthcare resources was undertaken by administering an e-survey to clinicians.
Considering a time horizon of one year, the analyses showed that FCM can be considered a dominant strategy in comparison to placebo for the treatment of CHF patients with ID.
Increasing utilization rates of FCM in the considered population may lead to national budget savings of 20–97 million Euros per year.
The present study supports the use of FCM in patients with CHF and ID. Data emerging from observational studies or registries in the future will be able to provide further evidence to confirm these conclusions.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/full/10.2217/cer-2019-0074

Acknowledgments

The authors would like to thank A Mortara (Policlinico di Monza, Monza) and F Oliva (Niguarda Hospital, Milan) who gave precious suggestions in the development of the questionnaire and the clinicians who participated in the collection of data: P Agostoni (Centro Cardiologico Monzino, Milan), G Di Tano (U. O. Cardiologia, Ospedale ASST di Cremona, Cremona), M Metra (Spedali Civili di Brescia, Brescia), F Oliva (Niguarda Hospital, Milan), M Senni and P Baio (ASST Papa Giovanni XXIII, Bergamo).

Financial & competing interests disclosure

The present study was funded by Vifor Pharma Italia Srl. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Open access

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

Supplementary Material

File (suppl_file.zip)

References

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•• Clinical study comparing ferric carboxymaltose (FCM) to placebo.
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•• Reference study for the developed model.
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Information & Authors

Information

Published In

History

Received: 12 June 2019
Accepted: 15 August 2019
Published online: 3 October 2019

Keywords: 

  1. budget impact analysis
  2. chronic heart failure
  3. cost–effectiveness analysis
  4. cost–utility analysis
  5. ferric carboxymaltose

Authors

Affiliations

Centre for Research on Health and Social Care Management (CERGAS), SDA Bocconi School of Management, Bocconi University, 20136 Milan, Italy
Simone Gerzeli
Department of Political and Social Sciences, University of Pavia, 27100 Pavia, Italy

Notes

*
Author for correspondence: Tel.: +39 02 5836 2729; [email protected]

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Ferric carboxymaltose for patients with heart failure and iron deficiency in Italy: cost–effectiveness and budget impact. (2019) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2019-0074

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