Table 1
Comparison of Oral vs Intravenous Iron.
| ORAL IRON | INTRAVENOUS IRON | |
|---|---|---|
| PRICE | INEXPENSIVE | EXPENSIVE |
| Administration | Administered everywhere | In-hospital administration |
| Efficacy in Heart Failure | Inconclusive efficacy | High efficacy |
| Adherence | Low adherence due to high intake frequency | High adherence due to single administration |
| Availability in Developing Country | Highly available | Rarely available |
Figure 1
Consort diagram flow of this study. HF: Heart failure, eGFR: estimated glomerular filtration rate, 6MWT: 6-minute walk test.
Table 2
Baseline characteristics.
| VARIABLE | GROUP/CATEGORY | P VALUE | |
|---|---|---|---|
| FERROUS SULPHATE (N = 27) | PLACEBO (N = 27) | ||
| Gender | |||
| Male | 15 (68.2%) | 11 (57.9%) | 0.3 |
| Female | 7 (31.8%) | 8 (42.1%) | 0.3 |
| Age (y.o) | 58 ± 9 | 57 ± 10 | 0.7 |
| BMI (kg/m2) | 23.90 ± 3.62 | 22.87 ± 2.88 | 0.8 |
| Hypertension | 19 (86.4%) | 16 (84.2%) | 0.6 |
| Diabetes | 13 (59.1%) | 11 (57.9%) | 0.9 |
| ADHF hospitalization | 17 (77.3%) | 16 (84.2%) | 0.4 |
| ACS hospitalization | 11 (50%) | 13 (68.4%) | 0.3 |
| Stroke | 2 (9.1%) | 3 (15.8%) | 0.5 |
| Gastrointestinal bleeding | 2 (9.1%) | 2 (10.5%) | 0.9 |
| Gastritis | 4 (18.2%) | 4 (21.1%) | 0.8 |
| History of CABG | 4 (18.2%) | 3 (15.8%) | 0.8 |
| History of PCI | 10 (45.5%) | 11 (57.9%) | 0.4 |
| Coronary Disease | |||
| Normal Coronary | 2 (9.1%) | 2 (10.5%) | 0.18 |
| 1 Vessel disease | 3 (13.6%) | 7 (36.8%) | |
| 2 Vessel disease | 3 (13.6%) | 1 (5.3%) | |
| 3 Vessel disease | 11 (50%) | 6 (31.6%) | |
| Not revascularize | 3 (13.6%) | 3 (15.8%) | |
| Atrial Fibrillation | 4 (16.7%) | 0 (0%) | 0.09 |
| Systolic BP (mmHg) | 127 ± 22 | 118 ± 19 | 0.06 |
| Diastolic BP (mmHg) | 70 ± 13 | 70 ± 15 | 0.8 |
| Peripheral pulse (x/min) | 79 ± 15 | 82 ± 16 | 0.9 |
| LVEF (%) | 34 ± 9 | 35 ± 11 | 0.7 |
| TAPSE (cm) | 1.82 ± 0.48 | 1.80 ± 0.45 | 0.9 |
| 6MWT (m) | 300 ± 85 | 309 ± 75 | 0.7 |
| NYHA Functional Class | 0.3 | ||
| I | 0 (0%) | 0 (0%) | |
| II | 11 (50.0%) | 11 (57.9%) | |
| III | 11 (50%) | 8 (42.1%) | |
| IV | 0 (0%) | 0 (0%) | |
| Haemoglobin (g/dL) | 11.6 ± 1.8 | 11.3 ± 1.0 | 0.6 |
| Ferritin (ng/mL) | 121 ± 108 | 110 ± 72 | 0.6 |
| Transferin saturation (%) | 15.6 ± 5 | 17 ± 7.6 | 0.4 |
| eGFR (mL/min) | 57 ± 30 | 51 ± 26 | 0.4 |
| NT-pro BNP (pg/mL) | 2810 ± 3116 | 3105 + 2354 | 0.7 |
| Lactic acid (mmol/L) | 1.4 ± 0.6 | 1.3 ± 0.6 | 0.4 |
| SGOT (U/L) | 18 ± 9 | 19 ± 6.6 | 0.6 |
| SGPT (U/L) | 18.6 ± 10.7 | 20 ± 13 | 0.6 |
| eGFR | 50.9 ± 26.2 | 57.4 ± 29.5 | 0.4 |
| Haematocrit (%) | 37.30 ± 5.41 | 33.58 ± 2.97 | 0.3 |
| Relative reticulocyte (%) | 1.3 ± 0.50 | 1 ± 0.43 | 0.2 |
| Erythrocyte (106/µL) | 4.4 ± 0.83 | 4.10 ± 0.57 | 0.6 |
| Leukocyte (103/µL) | 7.927 ± 2.2 | 7.938 ± 2.1 | 0.9 |
| Platelet (103/µL) | 294 ± 609 | 270 ± 736 | 0.2 |
| RDW (%) | 14.3 ± 1.8 | 15 ± 1.8 | 0.2 |
| MCV (fL) | 84 ± 6.2 | 83 ± 8.0 | 0.8 |
| MCH (pg) | 28 ± 2.2 | 28 ± 3.5 | 0.9 |
| MCHC (g/dL) | 33 ± 1.0 | 33 ± 1.4 | 0.5 |
| Medication | |||
| – Diuretic | 21 (95.5%) | 16 (84.2%) | 0.2 |
| – ACE-I/ARB | 22 (100%) | 19 (100%) | 1 |
| – Beta Blocker | 18 (81.8%) | 18 (94.7%) | 0.2 |
| – MRA | 9 (40.9%) | 6 (31.6%) | 0.5 |
| – Statin | 20 (90.9%) | 18 (94.7%) | 0.6 |
| – Antiplatelet | 20 (90.9%) | 15 (78.9%) | 0.3 |
| – Anticoagulant | 2 (9.1%) | 4 (21.1%) | 0.3 |
| – Digitalis | 2 (9.1%) | 2 (10.5%) | 0.9 |
[i] No significant baseline differences between groups. Abbreviation: BMI = body mass index, ADHF = acute decompensated heart failure, ACS = acute coronary syndrome, eGFR = estimated glomerular filtration rate, RDW = red cell distribution width, MCV = mean corpuscular volume, MCH = mean corpuscular haemoglobin, MCHC = mean corpuscular haemoglobin concentration, ACE-I = Angiotensin II converting enzyme inhibitor, ARB=Angiotensin II receptor blocker.
Figure 2
6MWT functional capacity, haemoglobin, and iron profiles after 12 weeks intervention. A. Significant functional capacity improvement in FS group compare to placebo. B–D. Ferrous sulphate significantly increase haemoglobin, ferritin, and transferrin saturation, and levels respectively compared to placebo.
Table 3
Primary Outcome Baseline and 12-Weeks Follow Up.
| VARIABLE | GROUP/CATEGORY | |||
|---|---|---|---|---|
| FERROUS SULPHATE (N = 27) | PLACEBO (N = 27) | |||
| BASELINE | 12-FU | BASELINE | 12-FU | |
| 6MWT Functional Capacity | 300 ± 85 | 349 ± 86 | 309 ± 75 | 305 ± 85 |
| Haemoglobin | 11.6 ± 1.8 | 12.6 ± 1.8 | 11.3 ± 1.0 | 11.2 ± 1 |
| Ferritin | 121 ± 108 | 207 ± 106 | 110 ± 72 | 112 ± 83 |
| Transferrin Saturation | 15.6 ± 5 | 28 ± 10 | 17 ± 7.6 | 20 ± 11 |
| NT-pro BNP | 2810 ± 3116 | 1645 ± 1289 | 3105 ± 2354 | 1262 (128 – 7424)a |
| LVEF | 34 ± 9 | 37 ± 10 | 35 ± 11 | 34 ± 12 |
[i] a = presented in median (min – max) due to abnormal data. Abbreviation: 6MWT = 6-minute walk test, NT-pro BNP = N Terminal pro Brain Natriuretic Peptides, LVEF = left ventricular ejection fraction.
Table 4
NYHA functional class after 12 weeks intervention.
| NYHA FUNCTIONAL CLASS | FERROUS SULPHATE | PLACEBO | CHI SQUARE P VALUE |
|---|---|---|---|
| I | 2 (9%) | 0 | 0.001 |
| II | 18 (82%) | 2 (10%) | |
| III | 2 (9%) | 17 (90%) | |
| Total | 22 | 19 |
[i] Lower proportion of NYHA class III in ferrous sulphate compared to placebo group. Abbreviation: NYHA = New York Heart Association.
Table 5
Adverse event and gastrointestinal side effects.
| EVENTS | FERROUS SULPHATE (N) | PLACEBO (N) | P VALUE |
|---|---|---|---|
| HF rehospitalization | 1/27 | 2/27 | 0.4 |
| Death | 1/27 | 2/27 | 0.4 |
| Severe gastrointestinal side effects | 2/27 | 2/27 | 0.4 |
| Minor gastrointestinal side effects | 5/27 | 7/27 | 0.1 |
| Total Events | 9/27 | 13/27 |
[i] Abbreviation: HF= heart failure.
Figure 3
NT-pro BNP and LVEF after 12 weeks intervention. A–B. No significant NT-pro BNP and LVEF respectively between both groups after 12 weeks intervention.