Transcript The South London Stroke Register

Primary and Secondary Prevention
of Ischaemic Stroke
David Hargroves,
SpR in Stroke Medicine,
SW Thames.
12th October 2004
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Incidence & Mortality
Third commonest
cause of death
Transition
24%
3% of world’s disability
Developed
12%
Each year in England &
Wales 110,000 suffer
their first stroke.
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Developing
64%
2
Incidence
Age specific rates per 1,000 population
rate per 1,000
25
Erlangen 1.48
London 1.14 P<0.001
Dijon 0.93
20
15
10
5
0
<45
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45-54
55-64
65-74
Age group
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75-84
>84
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Primary Prevention
• Modifying Vascular risks *
–Hypertension
–Hyperlipidaemia
–Hyperglycaemia
–Smoking
–Alcohol
Exercise
Weight reduction
Lower salt intake
*Warlow, C., C. Sudlow, et al. (2003). "Stroke." Lancet 362(9391): 1211-24.
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Primary Prevention
• Identify those most at risk and treat
aggressively* .
– Diabetic patients.
– Previous vascular disease.
– Continued smokers.
*Weih, M., J. Muller-Nordhorn, et al. (2004). "[Risk factors in ischemic
stroke. Review of evidence in primary prevention]." Nervenarzt 75(4): 324.
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Deciding exactly what an individuals risk is
The estimated 10 yr. risk of CAD in a hypothetical 55yr old man
and women according to levels of various risk factors. Lipids in
units of mg/dl.
Wilson,P.W. (1994) Am. J. Hypertension; 7:75.
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Hypertension
Arterovascular benefit from treating mild to moderate hypertension
from 17 controlled studies. CAD reduced by 16% and Stroke by
40%. Absolute benefit slightly less ( numbers above graphs).
Treatment for approximately 4-5 yrs prevented a CAD event or stroke
in 2% of patients; preventing death in 0.8% patients.
Herbert, P.R. et al (1993), Arch Intern Med; 153:576.
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High/normal <139/89
Normal <129/84
Framingham
Heart Study
results:
Optimal < 120/80
Cumulative incidence of cardiovascular events over
time in 6859 men and women who were initially free
of hypertension and cardiovascular disease. High/
normal BP compared to optimal BP was associated
with an adjusted hazard ratio for cardiovascular
disease of 1.6 in men and 2.5 in women.Vasan, R.S.
et al (2001), N Engl J Med; 345:1291.
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Primary Prevention
Hypertension
• Persistently elevated BP>
160/100 if no other risks.
• Persistently elevated
BP>140/90 if raised
cardiovascular risk.
NICE guidelines 18,
Newcastle group (2004)
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Primary Prevention
Hyperlipidaemia
A practice decision based upon a
cost/ risk local analysis.
NICE guidelines on Hyperlipidaemia and cardiovascular risk
2004 still pending
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Primary Prevention
Hyperglycaemia
• HbA1c < 7.5% if at risk of microvascular
disease and < 6.5% if at risk of vascular
disease *
*NICE guidelines (Excellence, N. I. f. C. (2004). Diabetes.)
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Diabetic Patients
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Secondary Prevention
• Antiplatelet agents
• Anticoagulation
• Carotid Surgery
• Modification of vascular risk factors
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Antiplatelet therapy
• Start 300 mg aspirin daily for 7-10
•
•
•
days
Ideally after brain imaging
Reduce 75mg thereafter
Avoids death or disabling stroke in 1 in
100 pts
RCP guidelines (I. S. W. Party (2004). national clinical
guidelines for Stroke - 2nd edition, Royal College of
Physicians.)
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Dipyridamole Plus Aspirin vs. Aspirin in
Patients with Vascular Disease (15 trials)
No. of
Events
Odds Ratio and 99%
Confidence Interval
% Odds
Reduction
Nonfatal MI
215
Nonfatal Stroke
465
23
Vascular Death
545
-3
All Vascular Events
1188
10
Nonvascular Death
214
-14
Total Deaths
750
0.50
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-4
-6
0.75
1.00
Dipyridamole
Plus Aspirin
Better
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1.25
1.50
Aspirin Alone
Better
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CAPRIE Study
Efficacy of Clopidogrel Bisulfate in Primary Analysis
Cumulative Event Rate, %
MI, Ischemic Stroke, or Vascular Death
Aspirin
16
Event Rate per Year
12
Clopidogrel
8.7%*
Overall
Risk
Reduction
5.83%
8
5.33%
4
P = 0.045
0
0
3
6
9
12 15 18
21 24
27 30 33 36
Months of Follow-Up
Although the statistical significance favoring PLAVIX (clopidogr el bisulfate) over aspirin was marginal ( P = 0.045),
and represents the result of a single trial that has not been re plicated, the comparator drug, aspirin, is itself effective
(vs placebo) in reducing cardiovascular events in patients with rec ent MI or stroke. Thus, the difference between
PLAVIX and placebo, although not measured directly, is substanti al.
*ITTOctober
analysis. 2004
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Plavix Package Insert.
Clopidogrel vs. Aspirin ?
• ‘Match’ study compared Aspirin with
•
Aspirin and Clopidogrel in patients who
had had a TIA or minor Stroke and were
already taking Clopidogrel.
No significant benefit achieved and
increase in bleeding in Clop. + ASA grp.
Diener, H. C., J. Bogousslavsky, et al. (2004). "Aspirin and clopidogrel compared
with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack
in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial."
Lancet 364(9431): 331-7.
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Choice of Antiplatelet
• Aspirin first line post TIA / CVA
• Aspirin plus Dipyridamole second line.
• Clopidogrel third line or in those
intolerant to Aspirin.
RCP guidelines (I. S. W. Party (2004). national clinical guidelines for
Stroke - 2nd edition, Royal College of Physicians.)
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Anticoagulation for AF
•
•
•
Anticoagulation should be started in every patient in
atrial fibrillation unless contraindicated
Should be considered for patients with ischaemic
stroke associated with mitral valve disease,
prosthetic heart disease or within 3 months of
myocardial infarction
Anticoagulation should be not be started until brain
imaging has excluded haemorrhage and until 14 days
have passed from onset of ischaemic stroke
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NNT to prevent
one stroke =22
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Access to Neurovascular (NV)Clinics
• Study of delay from initial event to clinic
•
•
assessment in three different localities;
offering daily, weekly and fortnightly NV
clinics.
377 enrolled.
No. of patients seen within 14 day
recommended window was 91%, 49%, 20%
respectively.
Giles, M. F., Flossman, E., Rotherwell, P.M. (2004). How frequent must
TIA and Stroke clinics be to satisfy guidelines on urgency of
assessment ? British Geriatric Society, Harrogate.
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Percutaneous Transluminal Angioplasty
Useful:
- Contraindications to CEA
- Stenosis at inaccessible sites
- Restenosis after CEA
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National Clinical Guidelines
• Any patient with carotid territory area stroke and with
minor or absent residual disability should be
considered for CEA
• Carotid ultrasound should be performed on all
patients being considered for CEA
• CEA should only be undertaken by a specialist
surgeon with a proven low complication rate, and
only if the stenosis is measured at greater than 70%
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Modifying vascular profile as secondary
prevention.
• Hypertension
• Hyperlipidaemia
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Hypertension
• Common –80%
• Multifactorial
• Hypertension associated poor outcome
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There is a Continuous Epidemiological Relationship Between Blood
Pressure Levels and Recurrent Stroke Risk
Stroke and usual BP among 2435 individuals with a
history of TIA or minor stroke.
4.00
4.00
2.00
2.00
Relative
risk of
1.00
secondary
stroke
Relative
risk of
1.00
secondary
stroke
0.50
0.50
0.25
0.25
75
80
85
90
95
Usual Diastolic BP (mmHg)
Rodgers A, MacMahon S, et al. BMJ. 1996:313:147
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120
130
140
150
160
170
Usual Systolic BP (mmHg)
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PROGRESS Objective
Randomized placebo controlled trial designed to
determine the effects of a blood pressure-lowering
regimen on the risks of stroke and other major vascular
events in hypertensive and non-hypertensive patients
with a history of stroke or TIA
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PROGRESS Collaborative Group. Lancet 2001; 358: 1033-41
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Stroke Risk Reduction
All participants
28% risk reduction
0.20
Proportion with event
95% CI 17 - 38%
P<0.0001
0.15
Placebo
Active
0.10
0.05
0.00
0
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PROGRESS Collaborative Group. Lancet 2001; 358: 1033-41
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4
(Years)
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Risk Reduction for Hypertensive
vs Normotensive Patients
Events/patients
Active Placebo
Stroke
Hypertensive
Favors
active
Favors
placebo
Risk reduction
(95%CI)
32% (17 to 44)
163/1464 235/1452
Non hypertensive 144/1587 185/1602
27% (8 to 42)
Total stroke
28% (17 to 38)
307/3051 420/3054
Major vascular events
Hypertensive
29% (16 to 40)
240/1464 331/1452
Non hypertensive 218/1587 273/1602
24% (9 to 37)
Total events
26% (16 to 34)
458/3051 604/3054
0.5
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PROGRESS Collaborative Group. Lancet 2001; 358: 1033-41
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1.0
Hazard ratio
2.0
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Secondary Prevention
Hypertension Targets
•
•
Targets are systolic BP < 140 and diastolic < 85 mmHg
– < 130/ 80 for patients with diabetes.
Reduction should be considered using a combination of
long acting ACE inhibitor (eg Perindopril or Ramipril) and
a thiazide diuretic (eg Indapamide)
RCP guidelines (I. S. W. Party (2004). national clinical guidelines for
Stroke - 2nd edition, Royal College of Physicians.)
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Secondary Prevention
Hyperlipidaemia
• If total cholesterol is > 3.5 then a high
•
dose statin is required.
e.g. Simvastatin 40mg or
Atorvastatin 20mg.
RCP guidelines (I. S. W. Party (2004). national clinical guidelines for
Stroke - 2nd edition, Royal College of Physicians.)
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Conclusions
• Clear evidence from good quality
research
• Challenge now is to implement change
• Therapeutic nihilism no longer justified
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Thank You
David Hargroves, SpR Stroke Medicine.
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