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Primary & Secondary Preventionin the older adult
What’s the evidence ?
Dr Terry QuinnChief Scientist Office/Stroke Association Senior Lecturer
Institute Cardiovascular & Medical Sciences
@DrTerryQuinn [email protected]
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Conflict of interest / disclosures
Honoraria, travel, research support:
Bayer
Boehringer Eingleheim,
Bristol Myers Squibb Pfizer Alliance
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Conflict of interest / disclosures
![Page 4: Primary & Secondary Prevention in the older ... - RCP London](https://reader033.vdocuments.mx/reader033/viewer/2022050604/6272eea735857c0cac6e868a/html5/thumbnails/4.jpg)
Conflict of interest / disclosures
I am co-ordinating editor of Cochrane Dementia
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Conflict of interest / disclosures
I am co-ordinating editor of Cochrane Dementia
…………and partial to a meta-analysis
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Conflict of interest / disclosures
I am co-ordinating editor of Cochrane Dementia
…………and partial to a meta-analysis
I began training in Clinical Pharmacology
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Conflict of interest / disclosures
I am co-ordinating editor of Cochrane Dementia
…………and partial to a meta-analysis
I began training in Clinical Pharmacology
…………prone to talking about clinical trials
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Conflict of interest / disclosures
I am co-ordinating editor of Cochrane Dementia
…………and partial to a meta-analysis
I began training in Clinical Pharmacology
…………prone to talking about clinical trials
I am a Geriatrician
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Conflict of interest / disclosures
I am co-ordinating editor of Cochrane Dementia
…………and partial to a meta-analysis
I began training in Clinical Pharmacology
…………prone to talking about clinical trials
I am a Geriatrician
…………..so, may say something pragmatic
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Primary & Secondary Preventionin the older adult
What’s the evidence ?
Dr Terry QuinnChief Scientist Office/Stroke Association Senior Lecturer
Institute Cardiovascular & Medical Sciences
@DrTerryQuinn [email protected]
![Page 11: Primary & Secondary Prevention in the older ... - RCP London](https://reader033.vdocuments.mx/reader033/viewer/2022050604/6272eea735857c0cac6e868a/html5/thumbnails/11.jpg)
Donald
73 this year
Retired from business but still active
Non-smoker, tee-total
Overweight, high LDL cholesterol
BP 148/82
Concerns over cognition but scored will on screening test
Current meds: Atorvastatin 80mg
Doc, should I take a blood pressure tablet and aspirin?
![Page 12: Primary & Secondary Prevention in the older ... - RCP London](https://reader033.vdocuments.mx/reader033/viewer/2022050604/6272eea735857c0cac6e868a/html5/thumbnails/12.jpg)
Donald
73 this year
Retired from business but still active
Non-smoker, tee-total
Overweight, high LDL cholesterol
BP 148/82
Concerns over cognition but scored will on screening test
Current meds: Atorvastatin 80mg
Doc, should I take a blood pressure tablet and aspirin?
![Page 13: Primary & Secondary Prevention in the older ... - RCP London](https://reader033.vdocuments.mx/reader033/viewer/2022050604/6272eea735857c0cac6e868a/html5/thumbnails/13.jpg)
Primary & secondary prevention in older adults with:
• Statins
• Antihypertensives
• Anti-thrombotics
• Other agents
• Lifestyle management
What should the next older adult cardiovascular RCT look like ?
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Adverse
event
risk
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Adverse
event
risk
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1
10
100
0 2 4 6 8 10 12 14 16 18 20
number of drugs taken
percen
t o
f p
ati
en
ts w
ith
AD
R
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Adverse
event
risk
CV risk
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Framingham (cardiac risk model)
Sex
Age
Cholesterol
HDL
Blood pressure
Diabetes
Smoking
GRACE (ACS risk model)
Age
Heart Rate
Systolic BP
Creatinine
CCF (Killip)
TIMI (ACS risk model)
Age
Risk factors
Aspirin
Angina
ECG change
Cardiac enzymes
ABCD2 (TIA risk model)
Age
Systolic BP
Clinical features
Duration
Diabetes Mellitus
CHADS2 (AF risk model)
CCF
Hypertension
Age
Diabetes Mellitus
Stroke
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Adverse
event
risk
CV risk
Trial
evidence
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Donald
73 this year
Retired from business but still active
Non-smoker, tee-total
Overweight, high LDL cholesterol
BP 148/82
Concerns over cognition but scored will on screening test
Current meds: Atorvastatin 80mg
Doc, should I take a blood pressure tablet and aspirin?
![Page 22: Primary & Secondary Prevention in the older ... - RCP London](https://reader033.vdocuments.mx/reader033/viewer/2022050604/6272eea735857c0cac6e868a/html5/thumbnails/22.jpg)
PROSPER RCT
N=5804
Around 3.5 years F.U
P: Age 70-82 years
I: Pravastatin 40mg
C: Placebo
O: CV events
Shepherd J ,
Lancet 2002
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PROSPER RCT
N=5804
Around 3.5 years F.U
P: Age 70-82 years
I: Pravastatin 40mg
C: Placebo
O: CV events
Shepherd J ,
Lancet 2002
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PROSPER RCT
N=5804
Around 3.5 years F.U
P: Age 70-82 years
I: Pravastatin 40mg
C: Placebo
O: CV events
Shepherd J ,
Lancet 2002
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PROSPER RCT
N=5804
Around 3.5 years F.U
P: Age 70-82 years
I: Pravastatin 40mg
C: Placebo
O: CV events
Shepherd J ,
Lancet 2002
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PROSPER RCT
N=5804
Around 3.5 years F.U
P: Age 70-82 years
I: Pravastatin 40mg
C: Placebo
O: CV events
Shepherd J ,
Lancet 2002
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Any CV event
cardiac event
stroke
PROSPER RCT
N=5804
Around 3.5 years F.U
P: Age 70-82 years
I: Pravastatin 40mg
C: Placebo
O: CV events
Shepherd J ,
Lancet 2002
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Shepherd J ,
Lancet 2002
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Adverse
event
risk
CV risk
1o or 2o
prevention
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Trial participant • Robust
• Cognitively intact
• Single morbidity
• Healthy lifestyle
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Trial participant • Robust
• Cognitively intact
• Single morbidity
• Healthy lifestyle
My patients • Frail
• Cognitive decline
• Multi-morbidity
• ‘Typical’ Glasgow
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Adverse
event
risk
CV risk
1o or 2o
prevention
Frailty
Morbidty
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Donald
73 this year
Retired from business but still active
Non-smoker, tee-total
Overweight, high LDL cholesterol
BP 148/82
Concerns over cognition but scored will on screening test
Current meds: Atorvastatin 80mg
Doc, should I take a blood pressure tablet and aspirin?
![Page 35: Primary & Secondary Prevention in the older ... - RCP London](https://reader033.vdocuments.mx/reader033/viewer/2022050604/6272eea735857c0cac6e868a/html5/thumbnails/35.jpg)
RR
130 mmHg BP
Blood pressure and all cause mortality
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RR
? 160 mmHg BP
Blood pressure and all cause mortality
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Yue-Bin,
BMJ 2018
N=4658
Mean age 92.1 years
Three year follow-up
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Yue-Bin,
BMJ 2018
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Ettehad,
Lancet 2015
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Xie X,
Lancet 2015
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Severe hypotension 5 RCTs 0.3% vs 0.1% RR 2.68 (1.21-5.89)
Xie X,
Lancet 2015
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Xie X,
Lancet 2015
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Xie X,
Lancet 2015
Is this old?
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Xie X,
Lancet 2015
Is this old?
Need to have
4 years left
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Musini VM,
CDSR 2009
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SPRINT RCT
N=9361
Around 3.3 years F.U
P: Age 68 (SD 9.4)
I: sBP<120mmHG
C: sBP <140mmHg
O: CV events
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SPRINT RCT
N=9361
Around 3.3 years F.U
P: Age 68 (SD 9.4)
I: sBP<120mmHG
C: sBP <140mmHg
O: CV events
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Hypotension 158 (3.4%) 93 (2.0) 1.7 <0.001
Syncope 163 (3.5%) 113 (2.4) 1.44 0.003
AKI 204 (4.4%) 120 (2.6%) 1.71 <0.001
E’lite abnormality 177 (3.8%) 129 (2.8%) 1.38 0.006
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Disability
Mortality
M.A.C.E
Hospital admission
Treatment burden
Care-home
Cognitive declineBP
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Adverse
event
risk
CV risk
What are
you trying
to prevent
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Donald
73 this year
Retired from business but still active
Non-smoker, tee-total
Overweight, high LDL cholesterol
BP 148/82
Concerns over cognition but scored will on screening test
Current meds: Atorvastatin 80mg
Doc, should I take a blood pressure tablet and aspirin?
![Page 53: Primary & Secondary Prevention in the older ... - RCP London](https://reader033.vdocuments.mx/reader033/viewer/2022050604/6272eea735857c0cac6e868a/html5/thumbnails/53.jpg)
ASPREE RCT
N=19,114
Around 4.5 years F.U
P: Age >70 (median 74)
I: Aspirin 100mg
C: Placebo
O: CV events
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ASPREE RCT
N=19,114
Around 4.5 years F.U
P: Age >70 (median 74)
I: Aspirin 100mg
C: Placebo
O: CV events
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Any death
HR 1.14
(1.01-1.29)
Major bleed
8.6 per 1000
versus
6.2 per 1000
HR 1.38
(1.18-1.62)
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Adverse
event
risk
CV risk
Should we be
stopping not
starting
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Donald
73 this year
Retired from business but still active
Non-smoker, tee-total
Overweight, high LDL cholesterol
BP 148/82
Concerns over cognition but scored will on screening test
ECG – atrial fibrillation
Current meds: Atorvastatin 80mg
Doc, should I take a blood pressure tablet and aspirin?
![Page 58: Primary & Secondary Prevention in the older ... - RCP London](https://reader033.vdocuments.mx/reader033/viewer/2022050604/6272eea735857c0cac6e868a/html5/thumbnails/58.jpg)
Primary prevention of stroke in AF
0
1
2
3
4
5
6
7
8
9
AFASK BAATAF CAFA SPAF SPINAF
No.
of s
trok
es (%
)
warfarin
control
AFAS=AF Aspirin Study
BAATAF=Boston Area Anticoag. Trial
CAF=Canadian AF anticoagulation
SPAF=Stroke prevention AF
SPINAF=Stroke prevention non-rheumatic AF
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Anticoagulation underused in elderly
50% of AF pts > 75 years
<20% of pts in AF studies > 75 years
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Anticoagulation underused in elderly
50% of AF pts > 75 years
<20% of pts in AF studies > 75 years
BAFTA trial – pragmatic, primary care trial
N=973; pts >75
ASA 75mg v. warfarin (INR 2-3)
Mant J Lancet
2007 370:493-503
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BAFTA trial
0
0.5
1
1.5
2
2.5
3
3.5
4
Major stroke
(ASA)
Major stroke
(warfarin)
Major bleed
(ASA)
Major bleed
(warfarin)
(%)
even
ts
*
NNT 50
Stroke HR 0.48 (0.28 – 0.80)
Bleed HR 0.96 (0.53 – 1.75)
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Pts age > 75
years
Apixaban(ARISTOTLE)
Dabigatran (RE-LY)
Edoxaban(ENGAGE AF-
TIMI 48)
Rivaroxaban(ROCKET AF)
Patients aged
> 75 years
5678
(31%)
7258
(40%)
8474
(40%)
6229
(44%)
Stroke/SE 0.71
(0.53-0.95)
0.67
(0.49-0.90)
0.83
(0.67-1.04)
0.80
(0.63-1.02)
Major bleed 0.64
(0.52-0.79)
1.18
(0.98-1.42)
0.83
(0.70-0.99)
1.11
(0.92-1.34)
Intracranial
bleed
0.34
(0.20-0.57)
0.42
(0.25-0.70)
0.40
(0.26-0.62)
0.80
(0.50-1.28)
GI bleeding Data not
available
1.79
(1.35-2.37)
1.32
(1.10-1.72)
Data not
available
Bo M
Eur J Int Med 2017
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Adverse
event
risk
CV risk
Which agent
offers the
most benefit
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Donald
73 this year
Retired from business but still active
Non-smoker, tee-total
Overweight, high LDL cholesterol
BP 148/82
Concerns over cognition but scored will on screening test
TSH 9 mU/L, normal T4 and T3
Current meds: Atorvastatin 80mg
Doc, should I take a blood pressure tablet and aspirin?
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To determine if there are multimodal clinical benefits from
levothyroxine treatment in older people with SCH
health-related quality of life,
cardiovascular disease,
muscle function, cognition, BP, BMI, waist circumference
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Levothyroxine vs placebo
HR 0.89 (95%CI:0.47-1.69) p=0.728
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ThyPRO39
Handgrip strength
Digit-symbol substitution
Cardiovascular events
Total and CVS mortality
Blood pressure
Body Mass Index
Weight
Waist circumference
Barthel index
IADL
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ThyPRO39
Handgrip strength
Digit-symbol substitution
Cardiovascular events
Total and CVS mortality
Blood pressure
Body Mass index
Weight
Waist circumference
Barthel index
IADL
X
X
X
X
X
X
X
X
X
X
X
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Adverse
event
risk
CV risk
Sometimes
there IS
enough
evidence
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Donald
73 this year
Retired from business but still active
Non-smoker, tee-total
Overweight, high LDL cholesterol
BP 148/82
Concerns over cognition but scored will on screening test
Current meds: Atorvastatin 80mg
Doc, should I take a blood pressure tablet and aspirin?
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INTERSTROKE
Lancet 2010
}Explains around 85% of all ischaemic stroke
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}Explains around 90% of all ischaemic stroke
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Adverse
event
risk
CV risk
There is more
to life than
drugs
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Donald
73 this year
Retired from business but still active
Non-smoker, tee-total
Overweight, high LDL cholesterol
BP 148/82
Concerns over cognition but scored will on screening test
Current meds: Atorvastatin 80mg
Doc, should I take a blood pressure tablet and aspirin?
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Adverse
event
risk
CV risk
RCT
Evidence
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Aspirin
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Statin
BP drugs
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Patients
Intervention
Control
Outcomes
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Patients – frail?
Intervention
Control
Outcomes
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Patients
Intervention – start or stop?
Control
Outcomes
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Patients
Intervention – start or stop?
Control
Outcomes – not just death & MI
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ASPREE RCT
N=19,114
Around 4.5 years F.U
P: Age >70 (median 74)
I: Aspirin 100mg
C: Placebo
O: CV events
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ASPREE RCT
N=19,114
Around 4.5 years F.U
P: Age >70 (median 74)
I: Aspirin 100mg
C: Placebo
O: CV events
Dementia
Disability
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ASPREE RCT
N=19,114
Around 4.5 years F.U
P: Age >70 (median 74)
I: Aspirin 100mg
C: Placebo
O: CV events
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Burton J,
Drugs & Ageing 2018
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SPRINT RCT
N=9361
Around 3.3 years F.U
P: Age 68 (SD 9.4)
I: sBP<120mmHG
C: sBP <140mmHg
O: CV events
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Primary & secondary prevention in older adults with:
• Statins
• Antihypertensives
• Anti-thrombotics
• Other agents
• Lifestyle management
What should the next older adult cardiovascular RCT look like ?
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Primary & Secondary Preventionin the older adult
What’s the evidence ?
Dr Terry QuinnChief Scientist Office/Stroke Association Senior Lecturer
Institute Cardiovascular & Medical Sciences
@DrTerryQuinn [email protected]