blood pressure targets in nephrology - hÔpital …nephro-necker.org/pdf/2017/10.pdf · blood...
TRANSCRIPT
Blood Pressure Targets in Nephrology
Is it time to reassess our goals ?
Dominique Guerrot
Nephrology Department & INSERM U1096 - Rouen University Hospital
Actualités Néphrologiques - Paris - April 24th, 2017
U1096
@dguerrot
COI Disclosure – D.Guerrot
• Travel & accommodation support
Roche, Amgen, Servier, Daiichi Sankyo,
Otsuka, Shire, Alexion, Sanofi, Vifor-Fresenius
• Industrial research funding
Amgen
• Honoraria
0
Hypertension : 1st modifiable cause of mortality
Ezzati et al. Lancet 2002
Blood pressure and CV mortality
Meta analysis
61 obs. studies
N = 958074
Perspective studies collaboration, Lancet 2002
Framingham: BP and CV mortality
Vasan et al. NEJM 2001
Observational studies
Interventional trials
Meta analysis - 2015
Ettehad et al. Lancet 2015
Expected effects of a decrease in BP
The lower the better … or not?
Staessen et al. Lancet 2001
Is there an optimal target ?
Arguedas et al. Cochrane 2009
Arguedas et al. Cochrane 2009
Conclusion…
Arguedas et al. Cochrane Database Syst 2009
Landmark studies
Design
• Open RCT
• 2 SBP targets
– « Standard » < 140 mm Hg
– « Intensive » < 120 mm Hg
• Objectives
– Primary : Composite / MI, angina, stroke, HF, CV mortality
– Secondary
Inclusion criteria (n=3)
Main exclusion criteria (n=20)
• Standing SBP < 110 mmHg
• Diabetes mellitus
• Stroke
• LVEF < 35% or instable HF
• eGFR < 20 ml/min
• Proteinuria > 1g/24h, GN, ADPKD
• Frail elderly patients
Systolic Blood Pressure
Study stopped
Mean follow-up 3.26 y
Primary outcome (composite)
Secondary outcomes : all-cause mortality
Which practical conclusion does SPRINT suggest ?
High CV risk patients + SBP > 130 mmHg
Antihypertensive therapy
SBP target < 120 mmHg
Even if > 75-80 yo …
If we decided to broadly apply SPRINT results …
• Redefinition of uncontrolled hypertensive pts :
• Addition of 1-2 treatments
– Compliance ?
– Tolerance ?
– Potential complications ?
• Closer follow-up unquestionable … feasible ?
If we decided to broadly apply SPRINT results …
Bress et al. JACC 2016
Normandie ? 400 000
In contradiction with the guidelines …
ESH/ESC 2013
In contradiction with the guidelines …
Analysis
• Benefit
– Mainly related to CV mortality and HF
– Not on stroke
– Idem HYVET / SHEP / SYST-Eur
• Direct impact of the target or role of the medications independently of BP ? …
SPRINT : A methodological exception
SPRINT : A methodological exception
Kjeldsen SE et al, Hypertension 2016
Unattended AOBP = Manual office SBP -15 mmHg
Filipovsky et al, Blood Pressure 2016
SPRINT : All-cause death / median SBP reached
Himes B et al. The SPRINT Data Analysis Challenge, NEJM 2017
BP targets in diabetic patients : ACCORD study
ACCORD Study Group, NEJM 2010
SPS3 Study
Benavente OR et al, Lancet 2013
• RCT : 3020 patients with prior stroke
• Follow-up 3.7 y
• Comparison btw SBP <140 mmHg & < 130 mmHg
• Primary objective : recurrence of stroke / cerebral hemorrhage
SPS3 : Main results
Benavente OR et al, Lancet 2013
• Main outcome : NS (HR 0.81, p=0.08)
• MI + CV mortality : NS (HR 0.84, p=0.32)
• Rare adverse effects
HOPE-3 : Patients with milder CV risk
Lonn EM et al., NEJM 2016
• RCT 12705 patients
– Intermediate CV risk (1%/y) (CV mortality 2.2%/y in SPRINT)
– No HTN, or HTN controlled without ACEi/ARB/HCTZ
• Candesartan+HCTZ vs placebo (& Rosuvastatine vs plac)
• 2 composite primary objectives :
– CV mortality, MI, stroke
– Idem + heart arrest, HF, coronary angioplasty
HOPE-3
Lonn EM et al., NEJM 2016
HOPE-3 : Main result
Lonn EM et al., NEJM 2016
• Significant increase in non-severe adverse effects
• Conclusion : No point in treating if initial BP < 140 without prior CV event
NS
HTN & progression of CKD
Klag MJ et al, NEJM 1996
• MRFIT study
• Incidence of ESRD according to initial BP
Hypertension
Chronic Kidney Disease
Prevented by antihypertensive Rx ?
X
Questioning the link … « Hypertensive Nephropathy » ?
International Consortium for Blood Pressure GWAS, Nature 2011
• 200000 caucasian patients
• SNPs associated with HTN
Questioning the link … « Hypertensive Nephropathy » ?
NS
International Consortium for Blood Pressure GWAS, Nature 2011
SPS3 : Effects on eGFR
Peralta et al, Circulation 2016
CKD patients in SPRINT
Aggarwal R et al. The SPRINT Data Analysis Challenge, NEJM 2017
CKD patients in SPRINT : Renal Outcomes
The SPRINT Research Group, NEJM 2015
CKD patients in SPRINT
Aggarwal R et al. The SPRINT Data Analysis Challenge, NEJM 2017
MDRD 1994 • PAS 125 vs 140
• 100% patients IRC ≥ 3
• Négatif / DFG si Pu<1g/j
Positif / DFG si Pu>1g/j
Négatif / Critère CV
AASK 2002 • PAS 128 vs 141
• 100% patients IRC ≥ 3
• Négatif / DFG
Négatif / Critère CV
REIN-2 2005 • PA 130/80 vs PAD 90
• 100% patients IRC ≥ 3
• Négatif / DFG
Négatif / Critère CV
HOPE-3 2016 • PAS 128 vs 134
• 3% patients IRC ≥ 3
• Négatif / DFG
Négatif / Critère CV
SPRINT 2015 • PAS 120 vs 140
• 28% patients IRC ≥ 3
• Négatif / DFG
Positif / Critère CV
SPS3 2013 • PAS 130 vs 140
• 16% patients IRC ≥ 3
• Négatif / DFG
Négatif / Critère CV
ADVANCE 2007 • PAS 135 vs 140
• 19% patients IRC ≥ 3
• Négatif / DFG
Positif / AlbU
ACCORD 2010 • PAS 120 vs 140
• 9% patients IRC ≥ 3
• Négatif / DFG
Négatif / Critère CV
1995 2000 2005 2010 2015 2017
General BP Targets in CKD : Updated EBM in 2017
Tsai WC et al, JAMA Int Med 2017
• 9 RCTs (MDRD, AASK, REIN-2, SPRINT, …)
• 8127 CKD patients
• SBP difference 4-13 mmHg
• Mean follow-up 3.3 y
Rate of GFR decline : NS
Tsai WC et al, JAMA Int Med 2017
ESRD : NS
Tsai WC et al, JAMA Int Med 2017
General recommendations & in CKD
Individualized BP targets in 2017 ?
• Insufficient EBM for a lower general target in CKD
– For renal outcomes
– For CV outcomes & mortality
• Patient-specific target according to ?
– CV risk / age / initial BP
– Diabetes / ADPKD / proteinuria
– Target organ damage
– Rx side-effects
– Patient’s choice & compliance to reinforced follow-up
– ...
En conclusion
Blood Pressure Targets in Nephrology
Is it time to reassess our goals ?
Dominique Guerrot
Nephrology Department & INSERM U1096 - Rouen University Hospital
Actualités Néphrologiques - Paris - April 24th, 2017
U1096
@dguerrot