novel aspects of anemia and iron management in renal ... · novel aspects of anemia and iron...
TRANSCRIPT
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Novel aspects of anemia and iron management in renal patients with or
without cardiorenal syndrome
Renal Unit, King’s College Hospital, London, UK
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2000
2002
2004
2008
2010
Killini 2012
2012
2018
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SCF, GM-CSF, IL-3
SCF, IL-1, IL-3, IL-6, IL-11
PluripotentStem Cell
Burst-Forming Unit-Erythroid Cells (BFU-E)
Colony-FormingUnit-ErythroidCells (CFU-E)
Reticulocytes RBCsErythro-blasts
Proerythro-blasts
About 8 Days
Erythropoietin
Iron
Hepcidin
Plasma Fe-Tf
Activation of HIF under hypoxic conditions
EPO gene
HIF-2αHIF-β
HRE
P300
HIF system
Hepcidin system
HIF-PH
Erythropoiesis
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Controversies Conference on Iron Management in CKD | March 27-30, 2014 | San Francisco, California, USA
Outline of lecture
• What‘s new in anemia management?
• What‘s new in iron management?
• What‘s new in patients with cardiorenal syndrome?
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Is there anything new in relation to target haemoglobin?
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Hb correction with ESA therapy 15
14
10
11
12
13
9
Hb
(g/d
l)
7
8
6
• Reduced transfusions• Improved QoL, esp. physical domain• Improved physical capacity• Positive cardiac effects
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15
14
10
11
12
13
9
Hb
(g/d
l)
7
8
6
• Reduced transfusions• ? Improved QoL / ↑exercise capacity• Increased CVS events, stroke, VTE• Increased cancer-related deaths
Hb correction with ESA therapy
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15
14
10
11
12
13
9
Hb
(g/d
l)
7
8
6
Hb correction with ESA therapy
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Safety Concerns in the TREAT Study
Pfeffer MA et al. N Engl J Med 2009;361:2019–2032.
Darbepoetin alfaPlacebo
5.0†
2.0‡
8.9§
7.5‡
2.6
1.1
7.1
0
2
4
6
8
10
Stroke Venous thromboembolic
event
Arterial thromboembolic
event
Cancer-related mortality*
Patie
nts
(%)
0.6
†, p<0.001 versus placebo‡, p=0.02 versus placebo§, p=0.04 versus placebo*Amongst patients with a history of malignancy at baseline
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EPO has non-erythropoietic actions
High EPO levels
VSMC [Ca2+]i
RAS activation ET-1
Thromboxane Prostacyclin
ADMA
NO
Hypertension
Platelet production Platelet activity
E selectin P selectin
vWF PAI-1
Thrombosis
VSMC proliferationEC proliferationAngiogenesis
Blood access stenosisProliferative retinopathy
Vascular remodelingTumor growth
Vaziri ND & Zhou X. Nephrol Dial Transplant 2009; 24: 1082–1088.
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Erythropoiesisrange
1000
100
10
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14Time (days)
EPO conc. (mU/mL) Three 40 U/kg SC doses/wk
Besarab et al, J Am Soc Nephrol 1992.
Two 60 U/kg SC doses/wkOne 120 U/kg SC dose/wk
Erythropoietin concentration-time profiles
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Ofsthun et al, Kidney Int 2003; 63: 1908-1914.
Hb predicts survival in observational studiesHD patients
If a patient is NOT on ESA therapy and has a high Hb, is there a need to
venesect / lose circuits?
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Hb predicts survival in observational studiesND-CKD patients
Levin A. et al, Nephrol Dial Transplant 2006; 21: 370-377.
Months from Hg Result
Prob
abilit
y of
Sur
viva
l
Survival of CKD Patients by Hemoglobin Level
0 3 6 9 12 15 18 21 24 27 30 33 36
0.70
0.75
0.80
0.85
0.90
0.95
1.00
Hemoglobin>= 130 g/L
120-129 g/L
110-119 g/L
100-109 g/L< 100 g/L Log-Rank Test: p =0.0001
If a patient is NOT on ESA therapy and has a high Hb, is there a need to
venesect?ABSOLUTELY NOT!
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What about the trigger haemoglobin to initiate ESA therapy?
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Hb
(g/d
L)
15
10
5
Declining GFR (mL/min)
When to initiate Hb therapy?
CKD stages 1–2 Stage 3
Stage 4
Stage 5
120–60 59–30 29–15 < 15
NHANES 3 data.
Caveats?• Hb < 11 g/dL plus symptoms• Individualisation
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What about the future of anaemia management in CKD?
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Erythropoiesisrange
1000
100
10
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14Time (days)
EPO conc. (mU/mL) Three 40 U/kg SC doses/wk
Besarab et al, J Am Soc Nephrol 1992.
Two 60 U/kg SC doses/wkOne 120 U/kg SC dose/wk
Erythropoietin concentration-time profiles
patient’s own EPO level
New strategy
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Transfusions ESAs HIF stabilisers
Evolution of CKD Anaemia Treatment
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HIF stabilisers – prolyl hydroxylase inhibitors
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Regulation of erythropoietin
Hypoxia-Inducible Factor (HIF)?
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Regulation of HIF activity
Inhibition of HIF under normoxic conditions
HIF-PHHIF-αHIF-α
HIF-α
Proteasome
OH OH
O2
OH OH
Proteasomal degradation
VHL
Activation of HIF under hypoxic conditions
Gene eg EPO
P300
HIF-PH
HIF-α
O2
HIF-α
HIF-β
HRE
HIF-α
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HIF stabilisers
• HIF is degraded by a prolyl hydroxylase enzyme
• Orally-active inhibitors of PH have been synthesised
• These drugs cause HIF levels to increase
• More HIF leads to more EPO
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HIF PHIs in development Company Molecule Drug name Phase of
developmentFibroGenAstellasAstra Zeneca
FG-4592 Roxadustat Phase 3
GSK GSK 1278863 Daprodustat Phase 3
AkebiaMitsubishiOtsukaVifor Fresenius
AKB-6548 Vadadustat Phase 3
Bayer BAY 85-3934 Molidustat Phase 2/3
Japan Tobacco Inc JTZ-951 Phase 1
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J Am Soc Nephrol 2016 Apr;27(4):1225-33.
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Besarab et al. J Am Soc Nephrol 2016 Apr;27(4):1225-33.
Roxadustat increases haemoglobin levels
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The Erythropoietic Response mediated by HIF
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Roxadustat lowers hepcidin levels
Provenzano et al. ASN 2012 Abstract
Roxadustat
EPO
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Besarab et al. J Am Soc Nephrol 2016 Apr;27(4):1225-33.
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Controversies Conference on Iron Management in CKD | March 27-30, 2014 | San Francisco, California, USA
Outline of lecture
• What‘s new in anemia management?
• What‘s new in iron management?
• What‘s new in patients with cardiorenal syndrome?
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Iron supplementation
Dietary iron Oral iron
IV iron
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Better Hb response with IV iron compared to oral or no iron
14
ESA + IV ironESA + oral ironESA + no iron
*p<0.05, **p<0.005 vs IV iron
6
8
10
12
0 4 8 12 16
Hb
(g/d
L)
*
****
****
Macdougall et al, Kidney Int 1996.
Time (weeks)
*
*
*
**
**
**
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Meta-analysis showed intravenous iron to be more favourable vs oral iron therapy in patients with ND-CKD
Rozen-Zvi et al. Am J Kidney Dis 2008;52:897–906.
Haemoglobin (Hb) level or change from baseline
• Most studies had short duration of follow-up
• More randomized trials are required
Stoves 2001Aggarwal 2003Charytan 2005van Wyck 2005Agarwal 2006Spinovitz 2006
Total (95% CI)Test for heterogeneity: Chi2 = 8.42, df = 5 (P=0.13), 2 = 40.6%Test for overall effect: Z=2.79 (P=0.005)
WMD (random) 95% CI
Weight %
WMD (random) 95% CI
Study or sub-category
Favours oral Favours IV
0-0.5-1 0.5 1
6.278.0416.1225.4518.7525.37
-0.52 (-1.33, 0.29)0.49 (-0.21, 1.19)0.25 (-0.19, 0.69)0.30 (0.02, 0.58)0.20 (-0.18, 0.58)0.60 (0.32, 0.88)
100.00 0.31 (0.09, 0.53)
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Oral iron – anything new?
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Controversies Conference on Iron Management in CKD | March 27-30, 2014 | San Francisco, California, USA
Newer oral iron preparations
• Ferric citrate
• Ferric maltol
• Liposomal (sucrosomial) iron
• Heme iron polypeptide
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Adapted from G. Barragán-Ibañez et al. Rev Med Hosp Gen Mex 2016;79:88-97.
Intestinal absorption of ironFerric citrateFerric maltol
Ferrous sulphateFerrous fumarateFerrous succinateFerrous gluconate
Heme iron polypeptide
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Controversies Conference on Iron Management in CKD | March 27-30, 2014 | San Francisco, California, USA
Ferric citrate as a phosphate-binder
Treatment Difference at Week 52 ANCOVA, p=0.8
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Mean Ferritin (ng/mL)
Active Control(n=135)
Ferric Citrate(n=252)
Baseline (Day 0) 609 593
Week 12 649 751
Week 24 652 846
Week 36 631 862
Week 48 619 881
Week 52 624 898
Change from Baseline at Week 52% Change from Baseline
152.5%
30551.4%
Least Squares Mean Difference at Week 52P-value
285<0.0001
41
Effect of phosphate-binders on ferritin
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Mean TSAT(%)
Active Control(n=135)
Ferric Citrate(n=252)
Baseline (Day 0) 31 31
Week 12 31 40
Week 24 31 40
Week 36 31 40
Week 48 29 41
Week 52 30 39
Change from Baseline at Week 52% Change from Baseline
-1-3.2%
825.8%
Least Squares Mean Difference at Week 52P-value
9<0.0001
42
Effect of phosphate-binders on TSAT
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43
% S
ubje
cts
Active Control
Ferric Citrate
Effect of phosphate-binders on IV iron use
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Controversies Conference on Iron Management in CKD | March 27-30, 2014 | San Francisco, California, USA
Active Control Mean ESA Units/Week
Ferric Citrate Mean ESA Units/Week
12,000
10,000
8,000
6,000
4,000
2,000
01st Quarter 2nd Quarter 3rd Quarter 4th Quarter
Effect of phosphate-binders on ESA dose
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What’s new with IV iron?
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Included 7 RCTs comparing higher-dose IV iron with lower-dose intravenous iron, oral iron, or no iron in patients treated with dialysis that had all-cause mortality, infection, cardiovascular events, or hospitalizations as outcomes
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Besarab et al, 2002
Single-center (US), open-label, randomized, prospective 6-month study in HD patients
N = 42
Primary outcome: EPO dose (40% lower)
No differences in hospitalizations or infection rate were noted
Each group had 1 admission for an infectious etiology (pneumonia in the control group, line-related sepsis in the study group)
R
IV iron dextran (25-150 mg/wk to maintain TSAT 20-30%)
IV iron dextran 4-6 x 100 mg doses to increase TSAT >30% and thereafter to maintain TSAT at 30-50%
(n=23 -- 17 completed)
(n=19 -- 15 completed)
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Coyne et al, 2007 (“DRIVE”)
Open-label, randomized, controlled, multicenter trial (37 US centers)
N = 134
6-weeks follow-up
Better Hb response (p<0.03)
13 infection episodes in 10 patients occurred in the control arm, and 12 infection episodes occurred in 8 patients in the IV iron arm
R
1 g of ferric gluconate (Ferrlecit) administered in 8 consecutive 125-mg doses
No iron
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Lewis et al, 2015
Phase 3, sequential, randomized, open-label trial (60 sites in the US and Israel)
N = 441
52-weeks follow-up
Primary outcome – phosphate level
12.5% of patients in the ferric citrate and 18.5% of patients in the control groups reported infection SAEs
R
Ferric citrate 1 g (210 mg ferric iron)
Calcium acetate (667 mg) or sevelamer (800 mg)
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Singh et al, 2006
Open-label, phase 3, randomized, multicenter trial (21 sites in the US and Mexico)
N = 188
PD patients
8-weeks follow-up
11 episodes of peritonitis: 6 (8.0%) in iron group and 5 (10.9%) in control group2 in each group were considered serious (no episode related to study drug)7 episodes of exit-site infection: 3 (4.0%) in iron group and 4 (8.7%) in control group
R
1000 mg of iron sucrose IV as a 300-mg infusion on days 1 and 15 and a 400-mg infusion on day 28
No iron
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UK Kidney Research Consortium : Renal Anaemia CSG
This investigator-led clinical trial is supported through an unrestricted grant from
§ UK multicentre prospective open-label 2-arm RCT of IV iron therapy in incident HD patients§ Lead investigator: Iain Macdougall§ Clinical Trial Manager: Claire White§ No of sites: 50§ No. of patients: 2080§ Commenced: November 2013§ Trial oversight: Glasgow Clinical Trials Unit§ Funder : Kidney Research UK
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PIVOTAL will be the largest, and longest duration RCT examining the safety of IV iron in HD patients
55 2141
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Proactive IV iron arm – IV iron 400mg/month
Up to 4 weeks
screening
R
Total study period approximately 4 years (event-driven)– 2 years recruitment; 2-4 years follow-up per patient
Reactive – minimalistic IV iron arm(give IV iron if ferritin<200 ug/l; TSAT<20%)
Incident new HD patients (0-12 mths)
On ESATime to all-cause
mortality or composite of MI, stroke, HF hosp
Primary endpoint(withhold if ferritin>700 ug/l; TSAT>40%)
Study design
Sample size: 2080 patients
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Primary endpoint • Time to all-cause death or a composite of non-fatal cardiovascular
events (MI, stroke, and HF hospitalisation) -- adjudicated by a blinded Endpoint Adjudication Committee
Secondary endpoints • Incidence of all-cause death and a composite of myocardial infarction,
stroke, and hospitalisation for heart failure as recurrent events. • Time to (and incidence of) all-cause death • Time to (and incidence of) composite cardiovascular event • Time to (and incidence of) myocardial infarction • Time to (and incidence of) stroke • Time to (and incidence of) hospitalisation for heart failure • ESA dose requirements • Transfusion requirements • EQ-5D QOL and KDQOL • Vascular access thrombosis • All-cause hospitalisation • Infections; hospitalisation for infection
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NETWORK OF SITESEnglandQueen Elizabeth Hospital, Birmingham; Heartlands Hospital,Birmingham; Royal Free, London, King’s College Hospital, London;Guy’s & St Thomas’, London; St Helier, Surrey; St George’s, London;Royal Liverpool Hospital, University Hospital Aintree; SheffieldTeaching Hospital; Lister Hospital, Stevenage; Salford Royal Hospital,Manchester; Manchester Royal Hospital; Queen Alexandra Hospital,Portsmouth; Kent & Canterbury Hospital, Leicester General Hospital,Hull Royal Infirmary; Freeman Hospital, Newcastle; Churchill Hospital,Oxford; University Hospital of North Staffordshire, Stoke-on-Trent;Southmead Hospital, Bristol; Royal Cornwall Hospital; NottinghamCity Hospital; Norfolk & Norwich Hospital; New Cross Hospital,Wolverhampton; Royal London Hospital; Wirral University TeachingHospital; Royal Shrewsbury Hospital, Royal Devon & Exeter Hospital,Royal Preston Hospital, St James’ Hospital, Leeds; HammersmithHospital, London; Royal Sussex Hospital, Brighton; Bradford Teaching Hospital; Coventry University Hospital; Southend University Hospital; Gloucestershire Royal Hospital; DerrifordHospital, Plymouth; Royal Berkshire, Reading
Wales Morriston Hospital, Swansea; University Hospital, Cardiff
ScotlandWestern Infirmary, Glasgow; Victoria Hospital, Kirkcaldy; NinewellsHospital, Dundee; Royal Edinburgh Hospital
N. IrelandBelfast City Hospital, Antrim Area Hospital; Daisy Hill Hospital,Newry; Altnagelvin Hospital, Derry
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• 2141 patients randomized – (first patient recruited November 2013)
• Follow-up: 0 – 54.4 months (median 26.9 months)
• 478 deaths
• 6035 SAEs
• 631 primary endpoints to accrue (estimated to reach this June 2018)
Where we are now
Hospitalisations
Death
Infections
Myocardial Infarction Safety
signals
StrokeHospitalisation for heart failure
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Controversies Conference on Iron Management in CKD | March 27-30, 2014 | San Francisco, California, USA
Outline of lecture
• What‘s new in anemia management?
• What‘s new in iron management?
• What‘s new in patients with cardiorenal syndrome?
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Recommendation Class Level Iron deficiency
Intravenous FCM should be considered in symptomatic patients with HFrEF and iron deficiency (serum ferritin <100 µg/L, or ferritin between 100–299 µg/L and transferrin saturation <20%) in order to alleviate HF symptoms, and improve exercise capacity and quality of life
IIa A
ESC Guidelines on Heart Failure 2016
Recommendation based on:FAIR-HF & CONFIRM-HF
Ponikowski P, et al. Eur J Heart Fail 2016 & EHJ 2016
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Iron deficiency but not anaemia is associated with:
The shift in the cardiology field
1. Jankowska EA et al. J Card Fail 2011;17:899–906; 2. Comin-Colet J et al. Eur J Heart Fail 2013;15:1164–72;
3. Klip IT et al. Am Heart J 2013;165:575–82
No iron deficiencyAnaemia
Irondeficiency
No anaemia
Iron deficiencyAnaemia
No iron deficiency
No anaemia
12
16
15
14
Peak
VO
2 (m
L/m
in/k
g)
17
13
Iron deficiency P<0.001Anaemia P=0.15Interactions P=0.94
Reduced exercise capacity1
No iron deficiencyAnaemia
Irondeficiency
No anaemia
Iron deficiencyAnaemia
No iron deficiency
No anaemia
*P<0.01†P<0.001
Poor outcome3
2
HR
(95%
CI)
for a
ll-ca
use
mor
talit
y
3
1
*
†
25
45
No iron deficiency
40
P=0.008
Glo
bal H
RQ
oL*
35
30
Iron deficiency
50
30No anaemia
45
P=0.941
Glo
bal H
RQ
oL
40
35
Anaemia
Reduced QoL2
*Minnesota Living with Heart Failure Questionnaire (MLHFQ):higher scores reflect worse HRQoL
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67
FAIR-HF: Ferric carboxymaltose significantly improved QoL in iron-deficient patients
Comin-Colet J et al. Eur Heart J 2013;34:30–8
KCCQ clinical summary score (total symptom score and physical limitations)
KCCQ QoL score
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FAIR-HF: Ferric carboxymaltose significantly improved QoL in iron-deficient patients
Comin-Colet J et al. Eur Heart J 2013;34:30–8
Ferric carboxymaltose
Placebo
40
6-minute walk test
50
0
P<0.001
P<0.001 P<0.001
4 12 24
Weeks after randomization
Cha
nge
in 6
-min
ute
wal
king
dis
tanc
e (m
)
30
20
10
0
-10
15
KCCQ overall score
20
0
P<0.001
P<0.001P<0.001
4 12 24
Weeks after randomization
Cha
nge
in o
vera
ll KC
CQ
sco
re
10
5
0
10
EQ-5D VAS score
15
0
P<0.001
P<0.001P<0.001
4 12 24
Weeks after randomizationC
hang
e in
EQ
-5D
vis
ual a
sses
smen
t sco
re
5
0
-5
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… and these improvements were evident in CHF patients with and without anaemia
Anker S et al. N Engl J Med 2009;361:2436–48
Self-reported patient global assessment NYHA functional class
SubgroupFerric
carboxymaltose, n
Placebo, n
Odds ratio
(95% CI)
P value for
interaction
Ferric carboxymalto
se, n
Placebo, n
Odds ratio
(95% CI)
P value for
interaction
Haemoglobin 0.98 0.51
≤12.0 g/dL 146 74 148 74
>12.0 g/dL 146 75 146 760.5 1 2 4 8
Favours placebo
Favours ferric carboxymaltose
80.5 1 2 4
Favours placebo
Favours ferric carboxymaltose
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CONFIRM-HF: Ferric carboxymaltose treatment leads to sustained improvements in 6MWT, fatigue, PGA and NYHA
6MWT, 6 minute walk test; FCM, ferric carboxymaltose; LSM, least squares mean; SE, standard error Ponikowski P et al. Eur Heart J 2015;36:657–68
Fatigue score
36
-0.4
0.2
-1.4BL
P=0.40
0.0
-0.2
P=0.002P=0.002
6 30 52
Fatig
ue s
core
cha
nge
from
bas
elin
e LS
M -0.6
-0.8
12 18 24 42 48
P=0.009
P<0.001
-1.0
-1.2
Weeks since randomization
FCM Placebo6MWT
36
10
40
-40BL
P=0.1630
20
P=0.001P<0.001
6 30 52
6MW
T ch
ange
from
ba
selin
e LS
M
0
-10
12 18 24 42 48
P=0.10 P<0.001
-20
-30
Difference of 33 ± 11 m
36
12
0
P=0.067
10
P=0.004
P<0.001
6 30 52
Odd
s ra
tio (9
5% C
I)
8
6
12 18 24 42 48
P=0.093
P<0.001
4
2
NYHA
Favo
urs
FCM
Favo
urs
plac
ebo
36
3.0
0.06
P=0.29
4.0
3.5
P=0.047
P=0.001
12 30 52
Odd
s ra
tio (9
5% C
I)
2.5
2.0
18 24 42 48
P=0.035
P=0.001
1.5
1.0
PGA
Favo
urs
FCM
Favo
urs
plac
ebo 0.5
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71
36
4
10
… with improved quality of life over time
Ponikowski P et al. Eur Heart J 2015;36:657–68
KCCQ
-2BL
P=0.25
8
6
P=0.41
P=0.010
6 30 52
Weeks since randomization
Ove
rall
KCC
Q s
core
cha
nge
from
base
line
LSM
2
0
12 18 24 42 48
FCM vs placeboLSM (95% CI)
1.8(–1.2, 4.8)
4.5(1.1, 7.9)
3.3(0.2, 6.4)
1.3(–1.9, 4.6)
5.0(1.6, 8.3)
P=0.035 P=0.004
36
4
10
EQ-5D VAS score
0BL
P=0.308
6
P=0.080
P=0.120
6 30 52
Weeks since randomization
EQ-5
D V
AS c
hang
e fro
mba
selin
e LS
M
2
12 18 24 42 48
FCM vs placeboLSM (95% CI)
1.5 (–1.4, 4.4)
2.6(–0.7, 5.9)
2.8(–0.2, 5.8)
2.8(–0.3, 5.9)
5.2(2.0, 8.5)
P=0.067
P=0.002
FCM Placebo
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Effect of iv-iron on kidney function
Treatment effect (mL/min/1.73m2):* 2.8 ± 1.5 3.0 ± 1.5 4.0 ± 1.7
P=0.054 P=0.049 P=0.017
weeks afterrandomization
Change in eGFRfrom baseline
(mL/min.1.73m2)
Ponikowski et al. 2015.
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IRONOUT: No improvements in exercise capacity with oral iron
Lewis GD et al. JAMA 2017;317:1958–66
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CKD was present in 35—70% of HF patients evaluated in cohort studies or subanalyses of randomized controlled trials
Prevalence of CKD in CHF
Shiba N & Shimokawa H. J Cardiol 2011;57:8–17
Study YearNumber
of patients
NYHA Age, years
Male, % EF, % eGFR <60,
% Outcome
Adjusted hazard comparing with pts without CKD for the
outcome
SOLVD-T 2000 2161 I–IV 60.7 81.5 24.7 35.7 All-cause mortality 1.41 for eGFR <60a
PRIME-II 2000 1906 III–IV 64.7 80.4 26.2 49 (eGFR ≤58)
All-cause mortality
1.91 for eGFR 44–582.85 for eGFR <44
DIG 2002 585 II/III: 85% 65 73.9 35 50 (eGFR ≤63.8)
All-cause mortality
1.6 for eGFR 47–64a
2.1 for eGFR 18–48a
McClellan 2002 665 – 75.7 40 38.4 38b All-cause mortality
1.24 at 1-year mortalityb
UK-HEART 2002 553 II/III: 98% 62.7 76 42 – All-cause
mortality
1.09 in each 10 µmol/L increase of
creatinine
CHARM 2006 2680 II–IV 65.3 66.6 38.5 36 CV death + HF hospitalization
1.54 for eGFR 45–59.9
1.86 for eGFR <45
ANCHOR 2006 59,772 – 71.8 54.2 NA 39.2All-cause mortality +
HF hospitalization
1.39 for eGFR 30–442.28 for eGFR 15-29
CHART 2008 920 II–IV 68.3 65.1 49.3c 42.7All-cause mortality +
HF hospitalization
1.31 for eGFR 30–591.56 for eGFR <30
JCARE-CARD 2009 2013 1.8 (mean) 71.5 58.7 44.8 70.3 All-cause
mortality1.26 for eGFR 30–592.48 for eGFR <30
amL/min; bCKD was defined by serum creatinine of ≥1.4mg/dL for women and ≥1.5 mg/dL for men; cdata were retrieved from the previous study that included 1154 patients
Note: BACK-UP slide (this slide is animated)
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75
0.1
Meta-analysis* on individual patient data: Significant improvements on patient outcomes
Anker SD et al. Eur J Heart Fail 2017.*Four studies were included: FER-CARS-01, FAIR-HF, EFFICACY-HF, CONFIRM-HF
n (%)FCM
(n=504)Placebo (n=335)
eGFR <60 mL/min per 1.73 m2 216 (43) 156 (47) Rate ratio(95%CI) P
CV hospitalization and CV death 69 (23.0) 92 (40.9) 0.009
HF hospitalization and CV death 39 (13.0) 60 (26.7) 0.011
CV hospitalization and all-cause death
71 (23.7) 94 (41.8) 0.009
HF hospitalization and all-cause death
41 (13.7) 62 (27.6) 0.011
All-cause hospitalization and all-cause death
108 (36.1) 118 (52.5) 0.060
HF hospitalization 22 (7.3) 43 (19.1) 0.003
CV hospitalization 52 (17.4) 75 (33.3) 0.004
All-cause hospitalization 89 (29.7) 99 (44.0) 0.056
1
Log odds ratio
10
Favours FCM Favours placebo
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76
In conclusion
No huge changes in anaemia management within the last few years1
HIF stabilisers represent the new ‘kid on the block’ for anaemia management in CKD2
Despite a recent meta-analysis we still do not know how much IV iron to give patients3
The PIVOTAL study should address some of the gaps in the evidence base for IV iron 4
For many CKD patients the latest ESC guidelines on the use of IV iron in heart failure may be relevant5