1. Stroke-treatment and management SAHD Naghme Adab

2. Stroke epidemiology • Incidence higher than acute coronary syndromes • Most prevalent neurological disorder in people under the age of 85yrs • Increased long-term mortality and morbidity • 29% die, 25% dependant • Direct cost of stroke is high- estimated lifetime cost 40,000Euros

3. Acute stroke • Early detection • Thrombolysis with intravenous recombinant tissue plasminogen activator: rt-PA • Benefit if given within 3 hrs ( best in 1st 90mins) • Need CT to make sure that there is no haemorrhage • Recent evidence suggests there may be benefit up to 4.5hrs (ECASSIII) • Main risk hemorrhage; ICH 6% in NINDs, 2.2%in SITS-MOST • Stroke symptoms present for at least 30 minutes • A clearly measurable deficit (NIHSS > 4) • Dose is 0.9mg/kg ( 10% as an iv bolus then 90% as continuous iv injection over 1hr), max 90mg • Long list of Contraindications ……

4. Haemorrhagic diathesis Manifest or recent severe bleeding Haemorrhagic retinopathy Recent (within 10 days) traumatic external cardiac massage (CPR), puncture of a non-compressible vessel Documented ulcerative GI disease within the last 3 months Oesophageal varices Arterial aneurysm, AV malformation Neoplasm with ↑ bleeding risk Severe liver disease Major surgery/trauma in last 3/12 Pregnancy Intracranial haemorrhage on CT Age <18 and >80 years Bacterial endocarditis,pericarditis Acute pancreatitis Oral anticoagulation (andINR >1.4) Blood sugar <2.8mmol/l or >22.2mmol/l. Platelets <100,000/mm3 Rapidly improving symptoms (eg over 30-60 minutes) Stroke within the last 3 months Symptoms suggestive of SAH, even if CT is normal Seizure at stroke-onset. Use of heparin in the previous 48 hours and a prolonged PT Pretreatment systolic BP >185 or diastolic BP >110 or aggressive management needed to lower it to these limits Prior stroke and concommitant diabetes Severe stroke assessed by NIHSS (>25) or by imaging NIHSS ≤ 4: relative CI (can be thrombolysed off-license) Contraindication:

5. Likelihood of Being Helpedvs. Harmed • SITS-MOST Lancet 2007 • Mortality 11.3% • Risk of important haemorrhage 1.7% • Number needed to treat: NNT = 3.1 • Number needed to harm: NNH = 30.1 • For every 100 patients treated with rt-PA • 32 will have a better final outcome • 3 have a worse final outcome and • 65 have an unchanged final outcome • Likelihood of helped verses being harmed (LHH) = (30/3) = 10 • Intravenous alteplase is 10 times more likely to help than harm eligible patients with acute ischemic stroke

6. Presentation beyond 4.5hrs • In 1st 48hrs • Aspirin 300mg for 2 weeks and then 75mg thereafter ( prevents 15 dependencies or deaths per 1000 treated) • Heparin- avoid even in AF. Consider if required 2 weeks after acute stroke

7. Other acute treatments • BP – • recent trial showed no evidence that acute management of raised BP helpful • Only useful if patient symptomatic • Hyperglycaemia – insulin therapy may be required ie glucose above 10mmmol/L • Raised temperature treated with paracetamol

8. Risk factors for stroke • Non-modifiable eg male, age, familial predisposition • Blood pressure- risk doubles for every 7.5mmHg increase in diastolic BP • Cholesterol – increase with total cholesterol, LDL cholesterol and low HDL levels • Cigarette smoking doubles risk of stroke • DM – 2-4 fold increase risk of stroke • AF – 4% annual risk ( increase to 12% if previous TIA/stroke) • Valvular heart disease- risk of 10-20% per yr • Carotid stenosis – risk is 2% per yr in asymptomatic stenosis of 75%, increase to 15% if recent event • OCP, HRT

9. TIA or Stroke • Completed major stroke • low risk of recurrence but morbidity and mortality of the event is high • TIA and minor stroke • high risk of recurrence but morbidity and mortality of event low

10. Risk of recurrent stroke • Risk after TIA • Cumulative risk 3.1% at 2 days, 5.2% at 7 days, 8.0% at 30 days and 9.2% at 90 days • ABCD2 • Thereafter risk is 5% per year, and 2-3% annual risk MI • Risk after stroke • Large atherosclerotic risk is 4% at 1 week, 13% at 1 month • Lacunar stroke is 0% at 1 wk and 2% at 1 mth

11. Risk according to aetiology • Large artery disease • One month: 12.6% • Cardioembolic disease • One month: 4.6% • Small Vessel Disease • One month: 3.4% • LAA 14% of cases but 37% of recurrences • a higher risk of subsequent stroke in patients with posterior circulation events compared with anterior (OR1/41.47; 95% CI 1.1–2.0

12. ABCD2 Scale (TIA Assessment) Age is 60 years or older → 1 point Blood pressure >140/90mmHg → 1 point Clinical features: 􀂃 Unilateral weakness 2 points 􀂃 Speech disturbance without weakness 1 point 􀂃 Other 0 points *Note, maximum score of 2 points Duration: 􀂃 > 60 mins 2 points 􀂃 10 – 60 mins 1 point 􀂃 < 10 mins 0 points Diabetes 1 point ABCD2 Score ....points (Total score 0-7) High risk patients (six to seven points): 8.1% two-day recurrent stroke risk ≥5 points should be seen in TIA clinic within 24 hrs or admit >1 episode in last wk: 30% risk of stroke within a wk → needs admission

13. Acute TIA • EXPRESS study showed reduction in risk if seen acutely • Seen in 1st phase median of 19 days, and in second phase in 24hours • Resulted in reduced risk of non fatal stroke, MI or death from 11.3% to 3.6% in second phase • A loading dose of aspirin 300mg plus clopidogrel 300mg • Next day aspirin 75mg + clopidogrel 75mg for 1 month • Then started on secondary prevention

14. Secondary prevention • Antiplatelet drugs reduce risk of vascular event (stroke, MI, vascular death) by 1-2% per year • Aspirin 75mg (relative risk reduction of 13%) • Dipyridamole MR 200mg bd ( NICE 2004 recommend taking for 2 yrs post stroke/TIA)IN combination with aspirin relative risk reduction of 20% compared to aspirin alone (ARR 1%) • Clopidogrel 75mg ( may be slightly better but more expensive: used in aspirin intolerant)

15. BP- aim for< BP 130/80 (RCP guidelines) • Thiazide and ACE inhibitors seem best • Drop of 10mm Hg reduce risk stroke by 30% • Cholesterol • Statin eg simvastatin 40mg • Lowering LDL cholesterol by 1.00mmol/L results in 19% reduction in risk of ischaemic stroke- ie benefit more than antiplatelet drugs • In all with cholesterol >3.5mmol/L • SPARCL study looked at cholesterol reduction in those with ischaemic stroke- showed an absoloute risk reduction of 2.2%

16. If in AF • Numerus trials show benefit of warfarin over aspirin in AF and PAF, even in elderly. • ARR in annual stroke rate from 4.5% to 1.4% • Anticoagulate with warfarin, aim INR2-3 • Risk from warfarin is haemorrhage of 1-2% per year ( ICH 0.3-0.6%)

18. Factors that increase risk of stroke in AF – CHADS2 classificationGage et al JAMA 2001; 285:2864 • Congestive heart failure (within 100 days) • Hypertension • Age > 75 • Diabetes Mellitus • prior Stroke or TIA (2 points)

19. Carotid endarterectomy • Symptomatic carotid stenosis • TIA and at least 50% symptomatic carotid stenosis assoc’d with a risk of stroke of approximately 20% during the 2 weeks prior to endarterectomy • 70% stenosis risk of stroke is high • Moderate stenosis 50-69% benefit if offered surgery in first few weeks and esp if male • End arterectomy if offered in 12 weeks results in relative risk reduction of stroke by 60% • Offset by surgical risk of death or stroke of 5% approx • Since risk of stroke highest in first few days- in small stroke offer surgery urgently • If large recent infarct best to delay surgery by 2 weeks ( risk reperfusion haemorrhage)

20. Who benefits most from CEA? • In CETC benefit from endarterectomy was: • greatest if done early • is greater in men than women • increased with age • decreased with time since last event • greater following stroke than TIA • greater for cerebral events than for ocular events • greater in patients with irreg/ulcerated plaque