Hypertension in Older People

Stephen Makin

Clinical Lecturer in Medicine for Older People

@stephenmakin

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Disclosures

No consultancies, lecture

fees, expert witness

patents, royalties, stock

ownership. No industry

grants.

‘No free lunch pledge’

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Outline

• Observational

• Interventional studies

• Why the difference?

• Guidelines

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Joan Marple

• 85 year lady.

• Retired, drives, independent in all ALDS,

• PMH: MI in 2004, hypertension hypothyroid.

• Prescribed: levothyroxine. Bendroflumethiazide 2.5mg

• Presents to falls clinic

• O/E BP 196/110, no postural drop.

• MDT assessment: single fall due to new bifocal glasses

• Plan: Referred for strength and balance training, screened for osteoporosis risk. Keen to keep

independent and active for as long as possible BGS Trent A

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What would you advise Joan’s GP to do?

A. Recheck BP and increase anti hypertensive medications if

needed?

B. Stop antihypertensive medication

C. Leave on 2.5mg Bendroflumethiazide

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‘Is there any point in blood pressure tablets at my age Doctor?’

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Observational studies

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Mortality of men aged 45–74 years related to systolic blood pressure

Framingham study, Port et al Lancet

2000;255:175-80 Slide by Prof D Stott BGS Trent A

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• BMJ 1988

• 561 Finnish over 85s

• Followed up for 5 years

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• Hypertension was associated with DECREASD mortality BGS Trent A

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• Hendriek 1998

• 835 Residents of Leiden 85+

• Followed up for 7 years

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Results

All cause mortality

85% if BP <125

59% if BP >200

No difference if adjusted for health status

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• Electronic health records 144,403 patients over 80 from 2001

to 2014. Follow-up <5 years.

• Decline in BP occurs in the 2 years before death

• Decline also occurs in patients who are NOT treated

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Treated

Not treated

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4658 patients 'oldest old' in China (mean age 92.1)

Follow-up for 3 years.

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Associations of systolic blood pressure with three year all cause mortality in study population of

Chinese oldest old people, in Cox models with penalised splines after adjustment.

Yue-Bin Lv et al. BMJ 2018;361:bmj.k2158

©2018 by British Medical Journal Publishing Group

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Associations of systolic blood pressure with three year cardiovascular and non-cardiovascular

mortality risk in study population of Chinese oldest old people, in Cox models with penalised

splines after adjustment.

Yue-Bin Lv et al. BMJ 2018;361:bmj.k2158

©2018 by British Medical Journal Publishing Group

Cardiovascular

mortality

Non-cardiovascular

mortality

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Ageing and arterial stiffness

De

Rezende

Mikael et al

Arq Bras

Cardiol

2017;

109:253

Slide by Prof D Stott BGS Trent A

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Risk factors that have ‘paradoxical’ association with clinical outcomes in older people

Blood pressure

Cholesterol

BMI

Subclinical hypothyroidism

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Well Miss Marple, it seems that the link between high blood

pressure and poor health is less certain in people in their 80s,

in fact some people even do better with higher blood pressure.

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Not too fast….

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Who does RCTs in 80 year olds anyway?

• Hypertension in Very Elderly HYVET Beckett 2008

• Active treatment - Indapamide +/- Perindropril versus Placebo

• 3845 participants

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Beckett NS et al. N Engl J Med 2008;358:1887-1898.

Mean Blood Pressure, Measured while Patients Were Seated, in the Intention-to-Treat Population, According to Study Group.

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Beckett NS et al. N Engl J Med 2008;358:1887-1898.

Kaplan–Meier Estimates of the Rate of End Points, According to Study Group.

Treat 40 people for 2

years to prevent one

death

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Beckett NS et al. N Engl J Med 2008;358:1887-1898.

Kaplan–Meier Estimates of the Rate of End Points, According to Study Group.

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How low to go?

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3. Forest plot of comparison higher (< 150‐160/95‐100 mHg) versus lower (< 140/90 mmHg) BP

target, outcome 1. All‐cause mortality.

Garrison SR, Kolber MR, Korownyk CS, McCracken RK, Heran BS, Allan GM. Blood pressure targets for hypertension in older

adults. Cochrane Database of Systematic Reviews 2017, 8. Art. No.: CD011575. DOI:

http:/dx.doi.org/10.1002/14651858.CD011575.pub2

<150-160 <140/90

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• 9361 persons >50 years (mean age 68, 28%>75yrs)

• Systolic BP of >130 mm Hg and increased cardiovascular risk but no diabetes

• Randomised to – systolic BP target of <120mmHg (intensive treatment) or <140mmHg (standard treatment).

• Primary outcome composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes

SPRINT – a Game Changer

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Amlodipine

Chlorthalidone

(or furosemide if eGFR <30)

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The SPRINT Research Group. N Engl J Med 2015;373:2103-2116BGS Trent A

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Primary Outcome and Death from Any Cause

The SPRINT Research Group. N Engl J Med 2015;373:2103-2116

SAEs related to the intervention

220 (4.7%) in intensive treatment

118 (2.5%) in standard treatment

HR 1.88; P<0.001

Stroke, MI, heart failure or

cardiovascular death

Death from ANY cause

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Date of download: 8/6/2018Copyright © 2016 American Medical

Association. All rights reserved.

From: Intensive vs Standard Blood Pressure Control and

Cardiovascular Disease Outcomes in Adults Aged ≥75 Years

A Randomized Clinical Trial

JAMA. 2016;315(24):2673-2682. doi:10.1001/jama.2016.7050

2636 participants mean age 80 years

Reduced all cause mortality in treatment group

73/1317 v 107/1319

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Date of download: 8/6/2018Copyright © 2016 American Medical

Association. All rights reserved.

From: Intensive vs Standard Blood Pressure Control and

Cardiovascular Disease Outcomes in Adults Aged ≥75 Years

A Randomized Clinical Trial

JAMA. 2016;315(24):2673-2682. doi:10.1001/jama.2016.7050

Also works

in frail

patients

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Substudy – SPRINT MIND• 8,626 (92.1%) who completed at least one follow-up

cognitive assessment

• Intensive treatment –incident MCI, HR 0.83, 95% CI: 0.71-0.97, p=0.02

incident dementia, HR 0.84, 95% CI: 0.67-1.05, p=0.12

MCI plus dementia, HR 0.86, 95% CI: 0.75-0.99, p = 0.03

Alzheimer's Association International Conference, July 22-26, 2018, Chicago, USA

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Less growth in WMH

• Follow-up MRIs in 454 at a median of 4 years

WML volume increased by 0.28 cm3 (95% CI: -0.03, 0.58) with intensive treatment

Compared to 0.92 (0.59, 1.24) in the standard treatment group (p=0.004)

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Adverse events

• Any SAE 48.4% versus 48.3%

• Hypotension, syncope, bradycardia electrolyte abnormality, injurious fall, AKI

• 23.8% v 23.1%

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Adverse events

Significantly differences between groups:

• Hypotension, 2.4% v 1.4%

• Fall with injury 11.6% v 14.6%

• Low sodium 5.2% v 3.4%

Nearly significantly:

• Electrolyte abnormality 4.6 v 3.3 (p=0.06)

• AKI 5.5 v 4.2 (p 0.07)

Less falls in

treatment group

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Critique of SPRINT

• Stopped early

• BP measured sitting position with patient alone in a room

• Not fully blinded

• Most benefit came from reduction in heart failure - and treatment group had more

diuretics

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Multi-dimensional health risks for older adults with hypertension

Dashed arrows

indicate the inter-

related nature of

health outcomes

The presence of one

condition tends to

increase risk of one or

more of the others

Slide by Prof D Stott BGS Trent A

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Observational Studies Interventional Studies

High BP may be protective High Blood pressure is associated with increased cardiovascular risk

What’s the

confounding

factor?

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Observational Studies Interventional Studies

High BP may be protective High Blood pressure is associated with increased cardiovascular risk

All patients included • Only included patients with hypertension

• Who could consent • Who lived in the community • And did not have postural

hypotension

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Guidelines

2017 US NIH

Ambulatory community dwelling adults

(>65 yrs)

Aim for SBP <130

If limited life expectancy

clinical judgment, patient preference,

and team-based approach to assess

risk/benefit

2018 ESC / ESH Guidelines

When treated, BP should be lowered

to a systolic value of 130–139 mmHg

and a diastolic value of <80 mmHg if

tolerated

Treated SBP values of <130 mmHg

should be avoided.

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Should we continue antihypertensive treatment in an older patient?

• Are they still hypertensive?

• Do they want treatment to reduce vascular risk?

• Do they have any adverse effects?

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Joan Marple

• 85 year lady.

• Drives, independent in all ALDS, active in church and Women’s Institute

• PMH: MI in 2004, hypertension hypothyroid.

• Prescribed: levothyroxine. Bendroflumethiazide 2.5mg

• Presents to falls clinic

• O/E BP 196/110, no postural drop.

• MDT assessment: single fall due to new bifocal glasses

• Plan: Referred for strength and balance training, screened for osteoporosis risk. Keen to keep

independent and active for as long as possible BGS Trent A

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What would you advise Joan’s GP to do?

A. Recheck BP and increase anti hypertensive medications if

needed?

B. Stop antihypertensive medication

C. Leave on 2.5mg Bendroflumethiazide

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Deprescribing ‘Stop and monitor’

Systematic review van der Wardt, 2017

26 small studies,

N<80

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FIGURE 4

Proportion of people remaining normotensive at 2 years or longer after antihypertensive treatment withdrawal.xxBased on the results for 3-year follow-up measurements; *using office blood pressure based on diastolic BP only; **using ambulatory blood pressure monitoring based on diastolic BP only; †men, bendrofluazide group; ††men propranolol group; †††women bendrofluazide group; ††††women propranolol group.

52

Withdrawal of antihypertensive medication: a systematic review

van der Wardt, Veronika; Harrison, Jennifer K.; Welsh, Tomas; Conroy, Simon; Gladman, John

Journal of Hypertension35(9):1742-1749, September 2017.

doi: 10.1097/HJH.0000000000001405

26%

normotensive

2 years later

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Stop and leave off: DANTE

• 385 patients

• 128 General Practices in Netherlands

• 75+

• MMSE 21-27

• 1:1 Allocation of discontinuing antihypertensive versus continuing

• Difference of 5.6mmHg between groups

• No improvement in cognitive function .

• No difference in cerebral blood flow

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Community versus hospital

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Evidence based management of hypertension in the hospital setting

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Eminence based management of hypertension in the hospital setting

SBP substantially lower than 120mmHg achieved with

intensive treatment in SPRINT In acute illness as well as stable patient

Approaching end of life (futility)

Adverse effectsPostural dizziness, falls or syncope with orthostatic hypotension, acute kidney injury

Best practice – but lacking empirical evidence to support

Slide by Prof D Stott BGS Trent A

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More research needed…

• Appropriate endpoints• ‘Dementia, disability and death’ instead of ‘MI, Stroke and Death’.

• Management of hypertension during the acute illness

• Safe de-prescribing

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Summary

• Anti-hypertensive medications are an effective treatment in older people who

have hypertension.

• Who want to take a treatment with an NNT of 40

• Blood pressure decreases with increasing frailty and therefore previously

hypertensive patients may no longer be hypertensive

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#UofGWorldChangers

@UofGlasgow

Thank you @StephenMakin

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