Drug Treatment in Secondary Prevention of Stroke

1
Drug Treatment in Secondary Prevention of Stroke
2
Burden of Stroke Mant J, et al. 2004Health
care needs assessment stroke. In Stevens A, et
al (eds) (2004). Health care needs assessment
the epidemiologically based needs assessment
reviews. Second Edition. Oxford Radcliffe
Medical Press.

• 46 of total NHS costs.
• The average GP (1800 pt list size) sees on
  average
• 3 new cases of stroke per year
• 1 new case of TIA every 18 months
• 1 recurrent stroke per year
• 1 new case of subarachnoid haemorrhage every 5
  years
• (Atrial fibrillation 7 new cases per year)
• The average GP has 30 existing stroke cases, of
  which 20 have moderate disability

3
Risk Factors for Strokehttp//www.rcplondon.ac.uk
/college/ceeu/strokeconciseauditreport.pdf

• The National Sentinel Audit of Stroke 2001
• Patients admitted into hospital with stroke in
  England, Wales N. Ireland

4
National Clinical Guidelines for Stroke Royal
College of Physicians. June 2004Secondary
Prevention

• Advice on lifestyle factors to all patients
• Stopping smoking
• Regular exercise
• Diet and achieving a satisfactory weight
• Reducing the intake of salt
• Avoiding excess alcohol
• Blood pressure
• Check and treat high blood pressure if it
  persists for longer than 2 weeks
• Use a thiazide or an ACE inhibitor or,
  preferably, a combination of both, unless
  contraindicated

5
National Clinical Guidelines for Stroke Royal
College of Physicians. June 2004Secondary
Prevention

• Antithrombotic treatment
• Antiplatelets for all patients with ischaemic
  stroke or TIA who are not on anticoagulation
  (aspirin, clopidogrel, or aspirin plus
  MR-dipyridamole) but note NICE guidance
• Anticoagulation if have persistent or paroxysmal
  AF
• No anticoagulant if in sinus rhythm unless there
  is a major source of cardiac embolism
• Anticoagulants should not be started until brain
  imaging has excluded haemorrhage and usually not
  until 14 days from the onset of the stroke
• Lipid-lowering agents
• A statin (e.g. simvastatin 40mg) if ischaemic
  stroke and TIA, and total cholesterol gt3.5 mmol/L
  unless contraindicated

6
National Clinical Guidelines for Stroke Royal
College of Physicians. June 2004Secondary
Prevention

• HRT
• Evidence suggests an increased risk of stroke for
  HRT
• Only after benefit/risk assessment and patient
  discussion
• Carotid stenosis
• Consider all patients with carotid artery
  territory stroke for endarterectomy
• Carry out as soon as patient is fit for surgery
  (preferably lt2 weeks)
• Carotid angioplasty is an alternative to surgery
• Specialist centres only

7
Which Antiplatelet Drug? A Detailed Review
Antithrombotic Trialists Collaboration BMJ
2002 324 7186

• Available evidence supports daily doses of
  aspirin in the range 75150mg for the long term
  prevention of serious vascular events in high
  risk patients.
• In clinical situations where an immediate
  antithrombotic effect is required (acute MI,
  acute ischaemic stroke, unstable angina), a
  loading dose of 150300mg should probably be
  given.
• Any real differences between two antiplatelet
  drugs are likely to be smaller than differences
  between antiplatelet therapy and no antiplatelet
  therapy.

8
NICE Says For Treatment Post StrokeNICE TA 090.
May 2005

• MR-dipyridamole and aspirin for 2 years following
  an ischaemic stroke or a TIA.
• Thereafter, or if MR-dipyridamole not tolerated,
  revert to standard care (including long-term
  low-dose aspirin).
• Clopidogrel (within licensed indication) if
  intolerant to low-dose aspirin
• i.e. if proven hypersensitivity to aspirin or
  history of severe dyspepsia induced by low-dose
  aspirin.

9
MATCH Ends Without a Result for
ClopidogrelDiener HC, et al. Lancet 2004 364
3317

• RCT of 7,599 high-risk patients with recent
  stroke already receiving clopidogrel 75 mg/day
• Clopidogrel vs Clopidogrel plus aspirin 75 mg
• Follow up 18 months
• Primary end point (ischaemic stroke, MI, vascular
  death, rehospitalisation for acute ischaemia)
• Aspirinclopidogrel 15.7 vs. clopidogrel 16.7
• RRR 6.4 (95 CI 4.6 to 16.3) NS
• Life threatening bleeds
• Aspirinclopidogrel 2.6 vs. clopidogrel 1.3
• Absolute increase 1.3 (95 CI 0.6 to 1.9) NNH
  77

Compared to monotherapy (clopidogrel), using a
combination of clopidogrel and aspirin may do
more harm than good
10
Blood Pressure Lowering in Stroke?

• Lowering BP in people after stroke (or TIA) is
  worthwhile.
• Good relationship between relative risk of stroke
  outcomes and BP reduction.
• Thiazide first line?
• RCP Guidelines use thiazide or an ACE inhibitor
  or, preferably, a combination of both, unless
  contraindicated.
• Poor evidence for beta-blockers.
• What optimum BP should we be aiming for?
• NICE hypertension guidelines ?140/90 mmHg (lower
  in people with diabetes).

11
PROGRESS Is It Really?Wennberg R Zimmermann
C. BMJ 2004 329 96871
12
Simvastatin 40 mg vascular event by prior
disease The Heart Protection Study. Lancet 2002
360 722
Risk ratio and 95 CI
Statin
Placebo
Baseline feature
(10269)
(10267)
Statin better
Statin worse
Previous MI
1007
1255
In people with CVA NNT 20 over 5 yrs to prevent
CVD
Other CHD (not MI)
452
597
No prior CHD


CVD
182
215
PVD
332
427
Diabetes
279
369
ALL PATIENTS
2042
2606
(19.9)
(25.4)
0.4
0.6
0.8
1.0
1.2
1.4
13
Summary

• Mortality, morbidity and disability are high
  after a stroke.
• The risk of recurrent stroke or other CV events
  can be reduced by secondary prevention
  strategies
• Lifestyle advice (and programmes).
• Antiplatelet treatment (low-dose aspirin plus
  dipyridamole for 2 years then revert to aspirin
  alone)
• BP lowering if hypertensive (first line diuretic
  and/or ACE inhibitor).
• Lipid-lowering (e.g. simvastatin 40mg).
• Note
• All these measures reduce, but do not abolish, CV
  events.
• For each additional intervention the incremental
  benefit decreases (law of diminishing returns).