What evidence is there for the use of iron dextran or iron sucrose in the heart failure patient population as an alternative to ferric carboxymaltose?

Comment by InpharmD Researcher

Several studies (Tables 1-4) demonstrated improvement in symptoms and reduction of New York Heart Association (NYHA) class using intravenous iron sucrose for anemic patients with heart failure. However, each study was limited significantly due to small sample sizes, lack of control group, and/or retrospective design. No robust data are currently available to recommend either iron dextran or sucrose over ferric carboxymaltose.
Background

The 2022 American Heart Association (AHA)/American College of Cardiology (ACC) and Heart Failure Society of America (HFSA) guidelines define iron deficiency as ferritin level <100 μg/L or 100 to 300 μg/L, if the transferrin saturation is <20%. Although the guidelines prefer intravenous (IV) to oral repletion of iron, they do not recommend a specific formulation of IV iron. Regardless, the majority of the cited data is driven by landmark trials of ferric carboxymaltose. There is no mention of iron sucrose or dextran in the guidelines. [1]

A 2019 review by the American College of Cardiology and Foundation notes that most studies in patients with heart failure (HF) and iron deficiency used either iron sucrose (maximum dose of 200 mg weekly) or ferric carboxymaltose (1,000 mg). The role of iron dextran in this patient population remains unclear. As most of the high-quality evidence is reported with ferric carboxymaltose, the authors particularly recommend its use in practice. [2]

A 2016 meta-analysis included five randomized controlled trials (N= 851 HF patients) to assess the effects of intravenous (IV) iron therapy in systolic heart failure (HF) patients with iron-deficiency anemia (IDA). One out of the five studies (N= 18) compared patients who received iron sucrose (200 mg, once a week, for 5 weeks) versus placebo in one of the three arms. The combined endpoints of cardiovascular death or hospitalization for worsening heart failure (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.24 to 0.63; p= 0.0001) as well as combined endpoints of all-cause death or cardiovascular hospitalization (OR 0.44, 95% CI 0.30 to 0.64; p<0.0001) and New York Heart Association (NYHA) class (−0.54 class, 95% CI −0.87 to −0.21; p= 0.001) were all significantly reduced after IV iron treatment. Moreover, there was a significant increase in 6-minute walking test distance (+31 m, 95% CI 18 to 43; p<0.0001) as well as an improvement in quality of life (Kansas City Cardiomyopathy Questionnaire [KCCQ] score +5.5 points, 95% CI 2.8 to 8.3; p<0.0001). The authors noted that the studies were generally heterogeneous in terms of treatment protocols, iron compounds, dosing, and duration, and the results of the meta-analysis were mainly driven by two studies. Although it was concluded that IV iron therapy generally alleviates HF symptoms and can improve HF outcomes in IDA patients, the specific preferred IV iron product remained uncertain. [3]

References:

[1] Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):1757-1780. doi:10.1016/j.jacc.2021.12.011
[2] von Haehling S, Ebner N, Evertz R, Ponikowski P, Anker SD. Iron Deficiency in Heart Failure: An Overview. JACC Heart Fail. 2019 Jan;7(1):36-46. doi: 10.1016/j.jchf.2018.07.015. Epub 2018 Dec 12. PMID: 30553903.
[3] Jankowska EA, Tkaczyszyn M, Suchocki T, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail. 2016;18(7):786-795. doi:10.1002/ejhf.473
Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

What evidence is there for the use of iron dextran or iron sucrose in the heart failure patient population as an alternative to ferric carboxymaltose?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-4 for your response.

 

Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial

Design

Prospective, randomized, open-label, observer-blinded, parallel, controlled trial

N= 35

Objective

To test the hypothesis that intravenous (IV) iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure (CHF) and iron deficiency

Study Groups

Control (n= 11)

IV iron (n= 24)

Inclusion Criteria

Aged ≥ 21 years; symptomatic CHF (New York Heart Association [NYHA] functional class II or III); exercise limitation as evidenced by a reproducible pVO2/kg ≤18 mL/kg/min during screening; an average of 2 screening Hb concentrations <12.5 g/dL (anemic group) or 12.5 to 14.5 g/dL (nonanemic group); ferritin <100 g/L or between 100 g/L and 300 g/L with a transferrin saturation (TSAT) <20%; left ventricular ejection fraction ≤45% measured within the preceding 6 months using echocardiography or magnetic resonance imaging; use of maximally tolerated doses of optimal CHF therapy for at least 4 weeks before recruitment and without dose changes for at least 2 weeks; resting blood pressure ≤160/100 mm Hg; and normal red cell folate and vitamin B12 (according to local laboratory reference ranges)

Exclusion Criteria

Use of erythropoietin, iron (oral or IV), or blood transfusion within the previous 30 days; a history of acquired iron overload or hemochromatosis (or a first relative with hemochromatosis); earlier hypersensitivity to parental iron preparations or a history of allergic disorders; active infection, bleeding, malignancy, or hemolytic anemia; presence of any condition that precluded exercise testing, such as decompensated heart failure, significant musculoskeletal disease, unstable angina pectoris, obstructive cardiomyopathy, severe uncorrected valvular disease, or uncontrolled brady- or tachyarrhythmias; concurrent immunosuppressive or renal replacement therapy; and chronic liver disease (alanine transaminase 3 times the upper limit of the normal range)

Methods

Eligible patients were randomized (2:1) to 16 weeks of IV iron (iron sucrose 200 mg weekly until ferritin 500 ng/mL, 200 mg monthly thereafter) or no treatment. Patients were stratified according to Hb levels (<12.5 g/dL vs. 12.5 to 14.5 g/dL). All patients continued to receive optimal conventional treatment for CHF and were scheduled to be seen at 1, 4, 8, 12, 16, and 18 weeks after randomization.

Duration

Between July 2004 and October 2005

Outcome Measures

Primary: change in absolute pVO2 (mL/min) from baseline to week 18

Secondary: changes from baseline to week 18 in pVO2 (mL/kg/min) adjusted for body weight, exercise duration, Hb, ferritin, TSAT, soluble transferrin receptor, left ventricular ejection fraction, changes from baseline to week 8 to 18 in NYHA functional class, patient global assessment on a 7-point scale, Minnesota Living With Heart Failure Questionnaire (MLHFQ) score, fatigue score (assessed using a 10- point visual analog fatigue scale, ranging from 1 for no fatigue to 10 for very severe fatigue) 

Baseline Characteristics

  

Control (n= 11)

IV iron (n= 24)

    

Demographics and clinical

Age, years

Male gender

Caucasian race

Body mass index (BMI), kg/m2

Ischemic etiology 

 

62 ±11

8 (73%)

10 (91%)

28 ± 5

8 (73%)

 

64 ±14

17 (71%)

21 (88%)

26 ±5

18 (75%)

    

NYHA functional class

II

III

 

6 (55%)

5 (45%)

 

13 (54%)

11 (46%)

    

Comorbidities

Coronary artery disease

Hypertension

Diabetes

Hyperlipidemia

 

8 (73%)

5 (45%)

4 (36%)

5 (45%)

 

19 (79%)

12 (50%)

8 (33%)

7 (29%)

    

Treatment

Diuretics

ACE inhibitors

Angiotensin II antagonists

Beta-blockers

Spironolactone

Digoxin

 

8 (73%)

8 (73%)

2 (18%)

11 (100%)

6 (55%)

2 (18%)

 

17 (71%)

18 (75%)

5 (21%)

20 (83%)

11 (46%)

6 (25%)

    

Results

Endpoint

Change ± SD

Treatment Effect (95% CI)

p-value
Control  IV Iron 

Primary endpoint

Absolute peak VO2, mL/min



-21 ± 120

 

75 ± 156*

 

96 (-12 to 205)

 

0.08

Secondary endpoint

Peak VO2/kg, mL/kg/min

Exercise duration, s

Transferrin saturation, %

Ferritin, ng/mL

Soluble transferrin receptor, mg/L

Hemoglobin, g/dL

Jugular venous pressure, cm

Weight, kg

NYHA functional class

Patient global assessment

MLHFQ score

Fatigue score

Left ventricular ejection fraction, %

 

-0.7 ±1.4

-15 ± 109

2 ± 7

51 ± 85

0.2 ± 0.6

0.4 ± 0.9

0.7 ±1.4

2.7 ± 4.0*

0.2 ±0.4

-0.2 ± 1.6

3 ± 19

0 ± 2

1 ± 5

 

1.5 ± 2.7*

45 ± 84*

13 ± 9‡

324 ±189‡

-0.1 ± 0.3

0.5 ± 1.2*

-0.1 ± 0.7

-1.8 ±3.9*

-0.4 ± 0.6*

1.5 ± 1.2

-10 ± 18*

-2 ± 2*

2 ± 5 

 

2.2 (0.5 to 4.0)

60 (-6 to 126)

11 (5 to 17)

273 (151 to 396)

-0.3 (-0.6 to -0.01)

0.1 (-0.8 to 0.9)

-0.8 (-1.5 to -0.1)

-4.6 (-7.5 to -1.6)

-0.6 (-0.9 to-0.2)

1.7 (0.7 to 2.6)

-13 (-26 to 1)

-2 (-3 to -1)

1 (-3 to 4)

 

0.01

0.08

0.001

<0.001

0.046

0.87

0.03

0.003

0.007

0.002

0.07

0.004

0.66 

Safety endpoints

Systolic blood pressure, mm Hg

Diastolic blood pressure, mm Hg

Heart rate, beats/min

Urea, mmol/L

Creatinine, µmol/L

Alanine transaminase, iU/L

C-reactive protein, mg/L

Malondialdehyde, µmol/L 

 

-1 ±17

1 ± 15

8 ±7†

0.7 ±5.3 

17 ± 49

0 ± 10

4 ± 9

0 ± 0.3

 

-1 ±12

0 ± 9

1 ±11

-0.6 ± 2.5

1 ±29

5 ±17

0 ±8

0 ± 0.2

0 (-10 to 10)

-1 (-8 to 6)

-7 (-14 to 1)

-1.3 (-4.0 to 1.3)

-16 (-43 to 11)

5 (-6 to 16)

-4 (-10 to 2)

0 (-0.2 to 0.1)

0.98

0.73

0.08

0.32

0.23

0.34

0.24

0.76

Patients with 1 or more adverse events (AEs)

7 (64%)

 10 (42%)    

Nonserious AEs

Abdominal pain

Coryzal symptoms

Cough

Gout

Transient ischemic attack

Heartburn

Pneumonia

Internal cardia defibrillator implantation

Decompensated HF (nonhospitalized)

 

0 (0%)

1 (9%)

2 (18%)

0 (0%)

0 (0%)

0 (0%)

1 (9%)

1 (9%)

1 (9%)

 

2 (8%)

2 (8%)

0 (0%)

1 (4%)

1 (4%)

1 (4%)

0 (0%)

0 (0%)

0 (0%) 

    

Serious AEs

Decompensated HF (hospitalized)

Symptomatic hyperthyroidism (hospitalized)

Death

 

1 (9%)

0 (0%)

0 (0%)

 

1 (4%)

1 (4%)

1 (4%) 

    

*p 0.05; †p 0.01; and ‡p 0.001 within-group differences compared with baseline

Adverse Events

See Results

Study Author Conclusions

Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism. Benefits were more evident in anemic patients.

InpharmD Researcher Critique

The small sample size limits the power to detect small differences between the treatment groups. The study utilized the last observation carry-forward method for imputing missing data which may have impacted the results. Given the chronic inflammatory state of HF patients, higher ferritin cutoffs (< 100 ng/mL) were implemented for defining iron deficiency. 



References:

Okonko DO, Grzeslo A, Witkowski T, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial. J Am Coll Cardiol. 2008;51(2):103-112. doi: 10.1016/j.jacc.2007.09.036

 

Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency

Design

Double-blind, randomized, placebo-controlled study

N= 35

Objective

To evaluate possible modifications in NT-pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels together with clinical and functional parameters, in a group of anemic patients with chronic heart failure (CHF) and chronic renal failure (CRF) receiving intravenous (IV) iron therapy, without recombinant human erythropoietin (rhEPO), versus placebo

Study Groups

Group A (n= 20)

Group B (n= 20)

Inclusion Criteria

LV ejection fraction (EF) ≤35%; New York Heart Association (NYHA) functional class II to IV; 3) anemia with an iron deficit defined by Hb <12.5 g/dL for men and <11.5 g/dL for women, and some of the following: serum ferritin <100 ng/mL and/or with transferrin saturation (TSAT) ≤20%; creatinine clearance ≤90 mL/min 

Exclusion Criteria

Hemodialysis therapy; anemia not due to iron deficiency available for erythropoiesis; NYHA functional class I; history of allergy to the iron supplements; acute bacterial infections, parasitism known in the 4 previous weeks, and neoplasm; chronic digestive diseases; hypothyroidism; congenital cardiopathies; receiving iron supplements in the 4 previous weeks; receiving rhEPO in the 4 previous weeks; and history of hospitalization during the 4 weeks before enrollment into the study were excluded from the study

Methods

Eligible patients were randomized to receive either IV isotonic saline solution (Group A) or IV iron sucrose complex 200 mg weekly (Group B) for 5 weeks. Monthly check-ups were carried out for the following 5 months during the follow-up phase.

Duration

Treatment phase: 5-weeks

Follow-up phase: 5 months

Outcome Measures

Primary: hematologic and renal parameters; change in the NT-proBNP levels and CRP

Secondary: number of hospitalizations, exercise tolerance, and change in the quality of life

Baseline Characteristics

  

Group A (n = 20)

Group B (n = 20)

    

Age (range), years

 74 ± 8 (60 to 89)  76 ± 7  (64 to 94)    

Etiology of CHF 

Coronary artery disease

Cardiomyopathy

Hypertension

Aortic valve disease

 

13

4

3

0

 

12

5

2

1

    

Each group was receiving similar medications for CHF.

Results

Endpoint

Baseline

Final (6-month follow-up)
Group A (n= 20) Group B (n= 20) Group A (n= 20) Group B (n= 20)
BMI, kg/m2 29.0 ± 3.4 28.7 ± 3.3 28.5 ± 3.2 26.7 ± 2.8*†
Heart rate, beats/min 80.5 ± 8.1 78.7 ± 8.2 76.3 ± 10.4 67.5 ± 5.9*†
Systolic blood pressure, mm Hg) 138.8 ± 8.3 139.7 ± 8.2 134.3 ± 7.3‡ 135.7 ± 6.1†
Diastolic blood pressure, mm Hg) 73.4 ± 7.5 74.4 ± 9.6 70.2 ± 6.6‡ 70.1 ± 8.3†
Hb, g/dL 10.2 ± 0.5 10.3 ± 0.6 9.8 ± 0.6 11.8 ± 0.7*†
Ferritin, ng/mL 70.6 ± 21.4 73.0 ± 29.9 78.9 ± 30.1 240.4 ± 55.6*†
TSAT, % 0.20 ± 0.01 0.20 ± 0.01 0.20 ± 0.01 0.25 ± 0.04*†
NT-proBNP, pg/mL 267.5 ± 114.9 255.9 ± 124.6 450.9 ± 248.8‡ 117.5 ± 87.4*†
C-reactive protein, mg/L 6.6 ± 4.3 6.1 ± 3.8 6.5 ± 3.7 2.3 ± 0.8*†
CrCl, mL/min 37.7 ± 10.2 39.8 ± 10.1 31.7 ± 10.8‡ 44.9 ± 11.0*†
EF, % 30.8 ± 1.7 31.3 ± 3.7 28.8 ± 2.4 35.7 ± 4.7*†
NYHA functional class 2.9 ± 0.6 2.9 ± 0.7 3.3 ± 0.6‡ 2.0 ± 0.2*†
MLHFQ score 58 ± 6 60 ± 5 59 ± 8 41 ± 7*†
6MW test, m 190.7 ± 56.1 192.3 ± 60.9 184.5 ± 58.5 240.1 ± 51.2*†
Number of hospitalizations - - 5/20§ 0/20

After 6 months follow-up, group B showed better hematology values and CrCl (p< 0.01) and lower NT-proBNP (117.5 ± 87.4 pg/mL vs. 450.9 ± 248.8 pg/mL, p < 0.01) and CRP (2.3 ± 0.8 mg/L vs. 6.5 ± 3.7 mg/L, p < 0.01). There was a correlation initially (p< 0.01) between Hb and NT-proBNP (group A: r= −0.94 and group B: r= −0.81) and after 6 months only in group A (r = −0.80). Similar correlations were observed with Hb and CRP. 

*p< 0.01 versus group A at final;†p< 0.01 versus group B at baseline;‡p< 0.05 versus group A at baseline;§p< 0.01 relative risk = 2.33 (95% confidence interval 1.59 to 3.42).

Adverse Events

There were no side effects reported in the 2 groups throughout the study.

Study Author Conclusions

Intravenous iron therapy without rhEPO substantially reduced NT-proBNP and inflammatory status in anemic patients with CHF and moderate CRF. This situation was associated with an improvement in LVEF, NYHA functional class, exercise capacity, renal function, and better quality of life.

InpharmD Researcher Critique

Results observed mainly surrogate laboratory markers. The study lacks robustness in evaluating clinical status. A large well-powered, randomized, placebo-controlled trial that is mortality-driven is warranted to confirm study findings. 



References:

Toblli JE, Lombraña A, Duarte P, et al. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol. 2007;50(17):1657-1665. doi: 10.1016/j.jacc.2007.07.029

 

Intravenous iron alone for the treatment of anemia in patients with chronic heart failure

Design

Prospective, uncontrolled, open-label study

N= 16

Objective

To assess the hematologic, clinical, and biochemical response to intravenous (IV) iron in patients with chronic heart failure (CHF) and anemia

Study Groups

All (N= 16)

Inclusion Criteria

Patients with systolic HF and Hb ≤12 g/dL who had been stable on standard HF medication for ≥6 weeks

Exclusion Criteria

Vitamin B12 or folic acid deficiency, hemoglobinopathy, or serum ferritin <400 ng/mL 

Methods

Eligible patients received a maximum of 1 g of iron sucrose by bolus IV injections over a 12-day treatment phase in an outpatient setting. Fourteen patients received 5 doses (1,000 mg) of iron sucrose, and 2 patients received 3 doses (mean dose 950 ± 137 mg)

Duration

Treatment intervention: 12 days

Mean follow-up: 92 ± 6 days

Outcome Measures

Hematologic parameters; symptoms and exercise capacity (MLHF score, 6MW distance)

Baseline Characteristics

  

All (N= 16)

  

Age, years

 68.3 ± 11.5   

Male

12 (75%)   

NYHA functional class

II

III

 

9 (56.3%)

7 (43.7%)

  

Left ventricular ejection fraction, %

 26 ± 13  

Results

Endpoint

All (N= 16)

p-value

Hemoglobin, g/dL

Baseline

Final

 

11.2 ± 0.7

12.6 ± 1.2 

0.0007

 

 

Serum iron, μmol/L

Baseline

Final

 

9.2 ± 4.4

13.7 ± 4.8

0.009

 

Ferritin, ng/mL

Baseline

Final

 

87 ± 113

217 ± 185

0.004

 

 

Transferrin saturation, %

Baseline

Final

 

16.0 ± 9.5

24.6 ± 8.4

0.009

 

 

NYHA functional class at final evaluation

II

III

 

16 (100%)

0 (0%)

<0.02

 

 

MLHF score

Baseline

Final

 

33 ± 19

19 ± 14

0.02

 

 

Mean 6MW distance, m

Baseline

Final

 

242 ± 78

286 ± 72 

0.01

 

 

Changes in MLHF score and 6-min walk distance related closely to changes in Hb (r= 0.76, p= 0.002; r= 0.56, p= 0.03, respectively). Of all baseline measurements, only iron and transferrin saturation correlated with increases in Hb (r= 0.60, p= 0.02; r =0.60, p= 0.01, respectively). 

Adverse Events

Iron sucrose was well tolerated with no instance of local or systemic adverse reactions. During follow-up, no patients were hospitalized, and none died.

Study Author Conclusions

Intravenous iron sucrose, when used without concomitant EPO, is a simple and safe therapy that increases Hb, reduces symptoms, and improves exercise capacity in anemic patients with CHF. Further assessment of its efficacy should be made in a multicenter, randomized, placebo-controlled trial.

InpharmD Researcher Critique

The findings merely represent a preliminary experience from an uncontrolled, open-label study. Treatment-related adverse events may have not been detected due to the small sample size. 



References:

Bolger AP, Bartlett FR, Penston HS, et al. Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol. 2006;48(6):1225-1227. doi: 10.1016/j.jacc.2006.07.015

 

The Use of Subcutaneous Erythropoietin and Intravenous Iron for the Treatment of the Anemia of Severe, Resistant Congestive Heart Failure Improves Cardiac and Renal Function and Functional Heart Failure Cardiac Class, and Markedly Reduces Hospitalizations

Design

Single-center, retrospective chart review 

N= 142

Objective

To evaluate the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization

Study Groups

All CHF patients (N= 142)

Intervention (n= 26)

Inclusion Criteria

Persistent, severe CHF (New York Heart Association [NYHA] class > III) despite at least six months of treatment in the CHF clinic, Hb level of <12 g%, resistant to maximally tolerated CHF therapy (including angiotensin-converting enzyme [ACE] inhibitors, the alpha-beta-blocker carvedilol, long-acting nitrates, digoxin, aldactone and oral and intravenous (IV) furosemide

Exclusion Criteria

Not explicitly specified

Methods

Eligible patients received the combination of subcutaneous (SC) erythropoietin (EPO) and intravenous (IV) Fe in an outpatient clinic. The EPO was given once a week at a starting dose of 2,000 IU per week subcutaneously, and the dose was increased or decreased as necessary to achieve and maintain a target hemoglobin (Hb) of 12 g%. The IV Fe (Venofer-Vifor International, St. Gallen, Switzerland), a ferric sucrose product, was given in a dose of 200 mg IV in 150 mL saline over 60 min every week until the serum ferritin reached 400 μg/liter or the percent Fe saturation reached 40% or until the Hb reached 12 g%. The IV Fe was then given at longer intervals as needed to maintain these levels.

Except for oral and IV furosemide therapy, the doses of all the other CHF medications, which were used in the maximum tolerated doses before the intervention, were kept unchanged during the intervention period.

Duration

7.2 ± 5.5 months

Outcome Measures

Clinical (death, hemodialysis); change in LVEF, NYHA class; hematological values (hematocrit [Hct], Hb, ferritin); serum creatinine; number of hospitalizations/patient

Baseline Characteristics

  

All patients (N= 142)

 

  

Age, years

70.1 ± 11.1

    

Female

21%     

Associated conditions

Diabetes

Hypertension

Dyslipidemia

Smoking

 

28%

64%

72%

40% 

    

Main cardiac diagnosis

Ischemic heart disease

Dilated CMP

Valvular heart disease

Hypertension

 

74%

15%

6%

5%

    

LVEF, %

32.5 ± 12.2

    

Previous hospitalizations/year

3.2 ± 1.5 

    

Lab values

Serum Na, mEq/liter

Serum creatinine, mg%

Hemoglobin, mg%

 

139.8 ± 4.0

1.6 ± 1.1

11.9 ± 1.5

    

NYHA class

I

II

III

IV

 

11 (7.7%)

26 (18.3%)

38 (26.8%)

67 (47.2%)

    
 

Intervention (n= 26)

    

CHF medications

ACE inhibitors

Carvedilol

Digoxin

Nitrates

Aldactone

Oral furosemide

IV furosemide

 

76.9% 

76.9%

96.2%

88.5%

73.1%

100% 

100%

    

CMP, cardiomyopathy; LVEF, left ventricular ejection fraction

The mean Hb level fell progressively from 13.73 ± 0.83 g% in class I NYHA to 10.90 ± 1.70 g% in class IV NYHA (p< 0.01).

The mean serum creatinine increased from 1.18 ± 0.38 mg% in class I NYHA to 2.0 ± 1.89 mg% in class IV NYHA (p< 0.001).

The mean ejection fraction fell from 37.67 ± 15.74% in class I to 27.72 ± 9.68% (p< 0.005) in class IV.

Results

Endpoint

Intervention (n= 26)
 

Initial

 Final p-value

NYHA class (0-4)

LVEF, %

3.66 ± 0.47

27.7 ± 4.8

2.66 ± 0.70

35.4 ± 7.6

< 0.05

< 0.001 

Hematological

Hct, %

Hb, %

Ferritin, μg/liter

 

30.14 ± 3.12

10.16 ± 0.95

177.07 ± 113.80

 

35.90 ± 4.22

12.10 ± 1.21

346.73 ± 207.40

 

< 0.001

< 0.001

< 0.005

Serum creatinine, mg%

2.59 ± 0.77

2.73 ± 1.55

 NS

No. hospitalizations/patient

2.72 ± 1.21

0.22 ± 0.65

 < 0.05

There were three deaths during the intervention period.

Three patients required chronic hemodialysis after 6, 16, and 18 months, respectively (serum creatinine at the onset of the anemia treatment were 4.2, 3.5, and 3.6 mg%, respectively).

Adverse Events

Not disclosed

Study Author Conclusions

The correction of the anemia is associated with an impressive improvement in cardiac function that is reflected in a marked improvement in the NYHA functional class, an improvement in renal function, and a striking reduction in hospitalizations and use of oral and IV furosemide. Treatment of the anemia with EPO and IV Fe may be a useful addition to the physicians’ armamentarium in CHF.

InpharmD Researcher Critique

Due to the single-center and retrospective nature, this study may be subject to selection bias. Additionally, this study was limited based on the small sample size and lack of a control group. 



References:

Silverberg DS, Wexler D, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol. 2000 Jun;35(7):1737-44. doi: 10.1016/s0735-1097(00)00613-6. PMID: 10841219.