ace hemmer / arb absetzen bei ckd stadium 4-5 · 2019. 5. 7. · • aceh/arb bis egfr 15-20 ml/min...
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ACE Hemmer / ARB absetzen bei CKD Stadium 4-5 ?
Johannes Mann
KfH Nierenzentrum München Isoldenstraßeund
Med. Klinik 4, Friedrich Alexander Universität Erlangen-Nürnberg
Heidelberg, April 2019
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I report the following potential dualities of interest :
Consultant: Boehringer, Celgene, Fresenius, Novo Nordisk, Vifor
Employee: KfH Research Support: European Union, Canadian Institutes
of Health Research, Univ. of Uppsala, AbbVie, Celgene, Idorsia, Novo Nordisk, Sanofi
Speaker’s Bureau: Boehringer, Fresenius, Medice, Novartis, Novo Nordisk, Roche, Sandoz
Stock/Shareholder: NoneTravel Support: In conjunction with above-mentioned
activities
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Frage an 703 Nephrologen (USA, KDOQI)
“Sollen ACE Hemmer / ARB abgesetzt
werden, wenn die eGFR bei progredienter
CKD unter 20 ml/min/1,73 m2 fällt? „
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Frage an 703 Nephrologen (USA, KDOQI)
“Sollen ACE Hemmer / ARB abgesetzt
werden, wenn die eGFR bei progredienter
CKD unter 20 ml/min/1,73 m2 fällt? „
Nein: 53,8%Ja: 46,2%
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ACE Hemmer / ARB absetzen bei CKD Stadium 4-5 ?
Heidelberg, April 2019
1) Vorteile der ACE Hemmer bei CKD-Für die Nieren-Für kardiovaskuläres System
2) Nebenwirkungen der ACE Hemmer bei CKD3) Warum eventuell absetzen ?
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(Jafar et al Ann Int Med 2001;135:73-87)
RR for ESRD: ACEI vs conventional drugs(meta-analysis of 1,860 patients of 11 trials)
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Lancet 2005;366:2026-34
Rel. risk for ESKD
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Lancet 2005;366:2026-34
Rel. risk for ESKD- Association with BP -
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Main outcomes in patients with CKD Mann, Gerstein, Pogue, Bosch, Yusuf, Ann Int. Med 2001;134:629-36
Prim. outcome
MI
CV Death All Death
PlaceboRamipril
Even
ts (p
er 1
000
pt-y
rs)
MI, stroke, CV death
MI
CV death Death
no CKD CKD no CKD CKD
no CKD CKD no CKD CKD
No CKD N= 6000, CKD N= 3500)
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Prim. Endpunkt:Kreatinin x2,Dialyse, Tod
Group 1:Krea 1.5-3 mg/dlGroup 2:Krea 3.01-5 mg/dl
Group 2: placebo
Group 1: benazepril
Group 2: benazepril
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Blutdruck und Proteinurie
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Beobachtungsstudie in Taiwan: 28.500 Pat. mit S-Kreatinin >6mg/dl,
50% mit, 50% ohne ACE Hemmer
Dialyse Dialyse oder Tod
Follow-up (months) Follow-up (months)
ACE/ARB
non-user
ACE/A
RB no
n-user
ACE/A
RB us
er
ACE/ARB
user
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ACE Hemmer / ARB absetzen bei CKD Stadium 4-5 ?
Heidelberg, April 2019
1) Vorteile der ACE Hemmer bei CKD-Für die Nieren-Für kardiovaskuläres System
2) Nebenwirkungen der ACE Hemmer bei CKD3) Warum eventuell absetzen ?
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ONTARGET: Risk of hyperkalemia in subgroups at high renal risk
Tobe, Clase, Gao, Teo, Yusuf, Mann. Circulation 2011;123:1098–1107
a
60eGFR Urine
albu
min
Macro-AMicro-A.Norm-A.
Macro-A
Micro-A.
Norm-A.
% with
K > 5.5 mmol/L
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Hyperkalemia, RAS-i and CKD
Hyper-K develops in approx. 10% of patients treated with RAS-i, within the 1st year.
Hyper-K in hospitalized patients is attributed to RASi in 15-38% of cases.
Reardon et al., Arch Int Med 1998;158:26 and Palmer, NEJM 2004;351:585
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Hyperkalemia, & K-binders patiromer and ZS-9 in RAS-i treated patients
Weir et al, NEJM 2015;372:211
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Hyperkalemia, & K-binders patiromer and ZS-9 in RAS-i treated patients
Weir et al, NEJM 2015;372:211 Anker et al., Eur J Heart Fail 2015;17:1050
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Hyperkalemia, & K-binders patiromer and ZS-9 in RAS-i treated patients
Weir et al, NEJM 2015;372:211 Anker et al., Eur J Heart Fail 2015;17:1050
Kalium
wird ges
enkt.
Werden
auch En
dpunkte
verbes
sert
durch di
e Mögli
chkeit R
AS-i we
iter zu g
eben?
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ACE Hemmer / ARB absetzen bei CKD Stadium 4-5 ?
Heidelberg, April 2019
1) Vorteile der ACE Hemmer bei CKD-Für die Nieren-Für kardiovaskuläres System
2) Nebenwirkungen der ACE Hemmer bei CKD3) Warum eventuell ACE Hemmer absetzen ?
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Langfristiger Verlauf der GFR: Abhängigkeit vom initialen Verlauf
Apperloo et al., Kidney Int 1997;51:793-7
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Stopping inhibitors of the renin-angiotensin system in patients with advanced CKD, N= 44
Ahmed et al, NDT 2010;25:3977
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Stopping inhibitors of the renin-angiotensin system in patients with advanced CKD
Ahmed et al, NDT 2010;25:3977
Before After stopping
BP (mmHg) 134/68 139/72
UPC (g/g) 0.8 1.25
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Gonc
alve
sAR,
El N
ahas
M e
t al
Nep
hron
Clin
ical
Pra
ctic
e 20
11: 1
19: 3
48-3
54
A >5ml improvement in GFR was predictive of dialysis or death
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Angiotensin Converting Enzyme inhibitor (ACEi) / Angiotensin Receptor Blocker (ARB) – To STOP OR Not
in Advanced Renal Disease
Prof Sunil BhandariConsultant NephrologistHonorary Clinical ProfessorInternational Director RCPE
EudraCT Number: 2013-003798-82MHRA CTA: 21411/0242/001-0001 (12th December 2013).Research Ethics Committee: Yorkshire and The Humber, Leeds East. Ref: 13/YH/0394. (29th January 2014).
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No ExcludedNot Meeting CriteriaDeclinedOther Reason
3 Ye
ar
Follo
w-U
p 3-monthly visits - routine tests (eGFR, FBC, BCP, urinary PCR), BP, documentation of ESA dose, adverse events, compliance and changes in medication
Extra tests at annual visits
- QOL questionnaire, weight and BMI, 6-minute walk test, ECG, and bloods for C-reactive protein, cystatin-C, NT-proBNP, ACE/renin levels and biomarkers
Yes
CKD patients stage 4-5ACEi/ARB treatments
Eligible for STOP-ACEi study?
Randomise1:1 ratio, N=410
Experimental Arm:Discontinue ACEi/ARB
N=205
Control Arm:Continue ACEi/ARB
N=205
2 ye
ars r
ecru
itmen
t3
year
s fol
low
-up
TARGET BP
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Participating sites – 38 UK Renal Units
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Frage an 703 Nephrologen (USA)
• “Sollen ACE Hemmer / ARB abgesetzt werden,
wenn die eGFR bei progredienter CKD unter
20 ml/min/1,73 m2 fällt? „
• Nein: 53,8%• Ja: 46,2%
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Meine Schlussfolgerung
• ACEh/ARB bis eGFR 15-20 ml/min nicht absetzen,
sofern keine NW (CV Vorteile und renale Vorteile
bei Proteinurie >1g/g).
• Wenn eGFR 15-20 ml/min erreicht und eGFR
Verlust >3ml/min/Jahr: ACEh/ARB pausieren und
eGFR, BD, Urin-Eiweiß beobachten, dann neu
entscheiden.
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E N D
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QJM: An International Journal of Medicine, Volume 101, Issue 7, 28 March 2008, Pages 519–527, https://doi.org/10.1093/qjmed/hcn039The content of this slide may be subject to copyright: please see the slide notes for details.
Nierenarterienstenose und ACE Hemmer
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QJM: An International Journal of Medicine, Volume 101, Issue 7, 28 March 2008, Pages 519–527, https://doi.org/10.1093/qjmed/hcn039The content of this slide may be subject to copyright: please see the slide notes for details.
Nierenarterienstenose und ACE Hemmer
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HF studies provide little information to direct care in advanced CKD - patients with significant renal dysfunction were excluded
Ahmed/Jorna/Bhandari DOI: Nephron 10.1159/000447068
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DM as a compelling indication for use of RAAS blockers: systematic review & meta-analysis of randomized trials?
Bangalore S et al. BMJ 2016; 352:i438.
19 RCTs25414 participants
No difference in • Death• CV death• MI• Angina• Stroke• HF• Renal Outcomes
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Effect of RAAS blockade in adults with diabetes mellitus and advanced CKD not on dialysis: a systematic review and meta-analysis
Nephrol Dial Transplant. Published online July 02, 2017. doi:10.1093/ndt/gfx072
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Effect of RAAS blockade in adults with diabetes mellitus and advanced CKD not on dialysis: a systematic review and meta-analysis
Nephrol Dial Transplant. Published online July 02, 2017. doi:10.1093/ndt/gfx072
FIGURE 2 All-cause mortality and CV mortality: ACEIs/ARBs versus placebo/other antihypertensive treatment.
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Effect of RAAS blockade in adults with diabetes mellitus and advanced CKD not on dialysis: a systematic review and meta-analysis
Nephrol Dial Transplant. Published online July 02, 2017. doi:10.1093/ndt/gfx072
FIGURE 3 Non-fatal CV events: ACEIs/ARBs versus placebo/other antihypertensive treatment.
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Effect of RAAS blockade in adults with diabetes mellitus and advanced CKD not on dialysis: a systematic review and meta-analysis
Nephrol Dial Transplant. Published online July 02, 2017. doi:10.1093/ndt/gfx072
Figure 4: Need for RRT/doubling of serum creatinine: ACEIs/ARBs versus placebo/other antihypertensive treatment
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Effect of RAAS blockade in adults with diabetes mellitus and advanced CKD not on dialysis: a systematic review and meta-analysis
Nephrol Dial Transplant. Published online July 02, 2017. doi:10.1093/ndt/gfx072
FIGURE 5 eGFR/CrCl (ml/min/1.73 m2), end-of-treatment values: ACEIs/ARBs versus placebo/other antihypertensive treatment.
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Angiotensin Converting Enzyme Inhibitor, Angiotensin Receptor Blocker Use, and Mortality in Patients With Chronic Kidney Disease
Miklos Z. Molnar; Kamyar KalantarZadeh et al J Am Coll Cardiol. 2014;63(7):650658.
Figure 1: survival probability of treated and untreated patients in the propensity score matched cohort, with ACEI/ARB treatment -association with lower mortality in both intention to treat and as treated models.
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Change in eGFR from Run-in