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 1 st 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. Contraindication: 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 80 years Bacterial endocarditis,pericarditis Acute pancreatitis Oral anticoagulation (and INR >1.4) Blood sugar 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)

5. Likelihood of Being Helped vs. 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 1 st 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 weakness2 points Speech disturbance without weakness1 point Other0 points *Note, maximum score of 2 points Duration: > 60 mins2 points 10 – 60 mins1 point < 10 mins0 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 1 st 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 classification Gage 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