controversies in hypertension what are the implication of ... · 2 years recruitment, 6 years max...
TRANSCRIPT
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Controversies in
Hypertension – what are the
implication of SPRINT in the
context of recent treatment
trials?Richard McManusDublin 2017
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Overview
SPRINT – what did it find?
SPRINT – nitty gritty details
Other intensive lowering trials
Meta analysis and Modelling
Conundrums and Conclusions
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SPRINT
NEJM 2015
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Inclusion & Exclusion
INCLUDED
Age of at least 50 years,
SBP 130 to 180 mm Hg
(medications <4)
AND increased risk CVD
– Clinical or subclinical CVD
– CKD (eGFR 20 – 60)
– 10-year CVD risk ≥15%
– Age ≥75 years
EXCLUDED:
Diabetes mellitus or prior
stroke
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Targets
SBP <120mmHg vs <140mmHg
Forced UP and DOWN titration to target
(If SBP <130 once or <135 twice then up
titrated in 140mmHg group)
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Outcomes
PRIMARY
Composite outcome of myocardial infarction, acute
coronary syndrome, stroke, acute heart failure,
or death from cardiovascular causes.
SECONDARYS included
Individual components of primary outcome,
Death from any cause, and the composite of the
primary outcome
or Death from any cause
Harms
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Blood Pressure Measurement
Automated Clinic BP measurement
Three readings mostly unattended
Mean of all three
Participant rested for 5 minutes
occasion
syst
olic
654321
146
144
142
140
138
136
134
132
130
Interval Plot of systolic vs occasion95% CI for the Mean
9mmHg drop over three readings
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Follow-up
Planned
2 years recruitment, 6 years max FU
What happened?
Trial terminated early
Median FU 3.6/5 years
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How do they compare to your patients?
10% not on anti HT Rx at baseline
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Results Blood Pressure
Mean SBP over trial: 122mmHg vs 135mmHg
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Primary Outcome
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NNT
Primary
61
Separation @1yr
Death any cause
90
Separation @2yrs
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CKD
The composite renal outcome for participants with CKD at baseline was the
first occurrence of a reduction in the estimated GFR of 50% or
more, long-term dialysis, or kidney transplantation.
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Subgroups
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Adverse Events
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Adverse Events (2)
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OVER 75
Williamson JAMA 2016
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Baseline over 75
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Outcomes over 75
Renal outcomes similar to all participants
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Frailty
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ACCORD
NEJM 2010
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Inclusion/ exclusion
Type 2 diabetes mellitus & HbA1c ≥7.5%
AND
– and were ≥40 years of age with CVD
– or ≥ 55 years of age with atherosclerosis,
albuminuria, left ventricular hypertrophy,or at least
two additional CVD risk factors
– a systolic blood pressure 130 -180mm Hg who
were taking three or fewer antihypertensives
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Exclusion
BMI ≥45,
creatinine ≥132.6 μmol/l
or serious illness.
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Factorial Design
Glycaemia, Lipids and BP
BP trial :
– SBP <120mmHg vs <140mmHg
– Forced UP and DOWN titration to target
– Half as many participants (4733)
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Baseline
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Blood Pressure
SBP difference: 119mmHg vs 134mmHg
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Outcomes
Primary = nonfatal myocardial infarction, nonfatal stroke, or death from
cardiovascular causes. The mean follow-up was 4.7 years.
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Harms
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SPS3
Lancet 2013
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Inclusion / exclusion
≥30 years
Normotensive or hypertensive,
Recent symptomatic, MRI-confirmed lacunar
stroke,
Without: Carotid Artery stenosis, disabling
stroke, haemorrhage or cortical stroke
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Targets
SBP 130–149 mm Hg vs <130 mm Hg.
– Forced UP and DOWN titration to target
– Third as many participants (3020)
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Baseline
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Blood Pressure
SBP: 138mmHg vs 127 mmHg
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Outcomes
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Harms
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META-ANALYSIS
Bangalore Am J Med 2017
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Inclusion & Searches
PubMed, EMBASE, and CENTRAL were
searched for randomized trials comparing
treating with different BP targets
Seventeen trials that enrolled 55,163 patients
with 204,103 patient-years of follow-up were
included.
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Results
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Efficacy vs Safety
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Treatment effect of lowering blood pressure similar regardless of baseline (>110mmHg systolic)
CHD risk reduction
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MODELLING
Bress Circulation 2016
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Modelled SPRINT to US Population
Prevent about 107,500 deaths per year eligible US
Adults (95%CI 93,300-121,200)
BUT
– 56,100 (95%CI 50,800-61,400) episodes hypotension,
– 34,400 (95%CI 31,200-37,600) episodes syncope,
– 43,400 (95%CI 39,400-47,500) electrolyte disorders,
– 88,700 (95%CI 80,400-97,000) cases AKI.
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BOTTOM LINE
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Conundrums & Conclusions
Early termination
No significant reduction stroke or MI
>90% on Rx at baseline (wrt baseline BP)
Adverse Events
BP measurement
Heterogeneity to other trials
Excluded stroke & DM
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Conundrums & Conclusions
Mortality & Primary Outcome Benefit
Consistent benefit across subgroups
If anything older & frailer groups did
better
Big trials vs meta analyses…
Consistent point estimates with
ACCORD & SPS3 which may have
been underpowered
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What do you think?
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Controversies in
Hypertension – what are the
implication of SPRINT in the
context of recent treatment
trials?Richard McManusDublin 2017