Controversies in

Hypertension – what are the

implication of SPRINT in the

context of recent treatment

trials?Richard McManusDublin 2017

Overview

SPRINT – what did it find?

SPRINT – nitty gritty details

Other intensive lowering trials

Meta analysis and Modelling

Conundrums and Conclusions

SPRINT

NEJM 2015

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

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)

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

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

Follow-up

Planned

2 years recruitment, 6 years max FU

What happened?

Trial terminated early

Median FU 3.6/5 years

How do they compare to your patients?

10% not on anti HT Rx at baseline

Results Blood Pressure

Mean SBP over trial: 122mmHg vs 135mmHg

Primary Outcome

NNT

Primary

61

Separation @1yr

Death any cause

90

Separation @2yrs

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.

Subgroups

Adverse Events

Adverse Events (2)

OVER 75

Williamson JAMA 2016

Baseline over 75

Outcomes over 75

Renal outcomes similar to all participants

Frailty

ACCORD

NEJM 2010

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

Exclusion

BMI ≥45,

creatinine ≥132.6 μmol/l

or serious illness.

Factorial Design

Glycaemia, Lipids and BP

BP trial :

– SBP <120mmHg vs <140mmHg

– Forced UP and DOWN titration to target

– Half as many participants (4733)

Baseline

Blood Pressure

SBP difference: 119mmHg vs 134mmHg

Outcomes

Primary = nonfatal myocardial infarction, nonfatal stroke, or death from

cardiovascular causes. The mean follow-up was 4.7 years.

Harms

SPS3

Lancet 2013

Inclusion / exclusion

≥30 years

Normotensive or hypertensive,

Recent symptomatic, MRI-confirmed lacunar

stroke,

Without: Carotid Artery stenosis, disabling

stroke, haemorrhage or cortical stroke

Targets

SBP 130–149 mm Hg vs <130 mm Hg.

– Forced UP and DOWN titration to target

– Third as many participants (3020)

Baseline

Blood Pressure

SBP: 138mmHg vs 127 mmHg

Outcomes

Harms

META-ANALYSIS

Bangalore Am J Med 2017

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.

Results

Efficacy vs Safety

Treatment effect of lowering blood pressure similar regardless of baseline (>110mmHg systolic)

CHD risk reduction

MODELLING

Bress Circulation 2016

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.

BOTTOM LINE

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

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

What do you think?

Controversies in

Hypertension – what are the

implication of SPRINT in the

context of recent treatment

trials?Richard McManusDublin 2017