Interventions for Stroke prevention

1. Interventions for Stroke prevention When, who, what?

2. Topics to cover Treatment of carotid stenosis Treatment of PFO Not Medical management AF management

3. Ischaemic stroke Atherothromboembolism 50% Small vessel disease 25% Cardioembolism 20% Other rarities 5% Atheroma and its complications are the most common cause of TIA and infarction. Small vessel disease within the brain about 25% of the total, and embolism from the heart another 20%. The rest are caused by rarer arterial disorders (eg arterial dissection) and blood disorders (eg sickle cell disease). Atheroma and its complications are the most common cause of TIA and infarction. Small vessel disease within the brain about 25% of the total, and embolism from the heart another 20%. The rest are caused by rarer arterial disorders (eg arterial dissection) and blood disorders (eg sickle cell disease).

4. Carotid stenosis is major cause of CVA Recent symptoms 28% 2-year risk CVA carotid stenosis >80% 0.3-2.4% of population Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991 Aug 15;325(7):445-453 Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991 Aug 15;325(7):445-453

5. Who to treat? Symptomatic carotid stenosis Asymptomatic carotid stenosis Pre CABG

6. Pre-requisites for success Prove surgery is better than tablets Prove percutaneous approach is almost as good as surgery Add stents/adjunctive therapy to make percutaneous BETTER THAN surgery

7.  Eastcott/ Debakey 1953 CEA Symptomatic NASCET (659) >70% stenosis 2-yr fu CVA 9% vs 26% on medical Rx ECST (3024) >60% stenosis 3-yr fu CVA 14.9% vs 26.5% on medical Rx Asymptomatic ACAS >60% stenosis 5-yr fu CVA 5.1% vs 11% on medical Rx ASCT >80% stenosis 5 year fu CVA

8. How severe a stenosis? Asymptomatic >80% Symptomatic >70% on angio Possibly lower (US 50%)

10. Quantify the risk of the procedure Asymptomatic stenosis 60% stenosis Medical Rx CVA/death 2.2% 1 year CEA CVA/death 3% 30 day >80% Medical Rx CVA/death 5.5% 1 year CEA CVA/death 4.6% 30 day

11. Choose your surgeon Stroke/death <3% in asymptomatic patients Does it regularly CEA is a great operation BUT…………..

12. recurrent hemisspheric TIA;high grade ICA stenosis

13. Prove percutaneous approach is almost as good as surgery CAVATAS Randomisation 1992-1997 560 pts 504 PTA vs surgery 86% stenosis Only 55 stents used One CVA at time of stent.

14. CAVATAS 3 year death/CVA or CVA ipsilateral –no difference Restenosis did not lead to changed outcome, but short FU.3 year death/CVA or CVA ipsilateral –no difference Restenosis did not lead to changed outcome, but short FU.

15. World wide CAS

18. Why have a stent program? CEA tricky Restenosis Not C2-C7 Hostile neck RT Surgery Scars High risk Medical Morbidity Neuro Morbidity RLN palsy contralat CAS Minimally Invasive No scar No GA Easy Equivalent Treatment of occlusion post CEA

19. The real life data CEA (VSSGBI) Mortality 1.3% LOS 3.9d Death/Stroke risk 3% CAS (World registry) Mortality 1% LOS 1.8d Death/Stroke risk 3% Death/stroke risk 1.8-2.8%

20. Sapphire Trial

21. Results at 30 days

22. Sapphire trial 1 year data

23. Choose your procedure?

24. Flanders study

26. And Now~? German trial French Trial Doubt about safety of CAS

31. Meta-analysis

32. Endovascular vs Surgical treatment of Carotid Stenosis:Any Stroke or Death at 30 days – Random effects method

33. Numbers of patients included in the meta-analysis of Symptomatic Carotid Surgery Trials P Rothwell et al. Lancet 2003;361:107-116 Carotid surgery versus medical care Outcomes: 3202 strokes & deaths J Ederle at al. Cochrane Review in prep.Carotid surgery vs Endovascular treatment Safety outcomes: 210 strokes & deaths

34. CAVATAS Intention to treat analysis  Carotids fit for surgery (n=504) Events within 30 days of treatment Event Endovascular Surgical treatment treatment All strokes*/death 10.0% 9.9% NS * More than 7 days duration Myocardial infarction 0% 0.8% NS Cranial nerve palsy 0% 8.7% <0.0001 Haematoma† 1.2% 6.7% <0.002 †requiring surgery or prolonging stay

35. Endovascular vs Surgical treatment of Carotid Stenosis: Any Stroke, Cranial Neuropathy or Death at 30 days

36. Endovascular vs Surgical treatment of Carotid Stenosis:Disabling Stroke or Death at 30 days

37. Conclusion The carotid is 25 years behind the coronary It is catching up fast. Different vessel and vascular bed (cf diabetes) The multidisciplinary team We have a program up and running

38. The present Symptomatic carotid stenosis >70% (?50%) CEA or CAS High risk, then CAS Get it done within 3 weeks Asymptomatic carotid stenosis >80% CEA or CAS High risk, then should you be doing it at all? Pre CABG Do one side if bilateral stenosis CAS would be a good choice

39. Should we close holes in the heart?

40. Cardiac Sources of Stroke 20% of neurological events may be cardiac 40% of neurological events are cryptogenic ? Are these often cardiac? Rheumatic heart disease AF Cardiomyopathy (clot) Aortic atheroma Patent Foramen Ovale

41. Other investigations History suggestive of arrthymia, syncope, cardiac cause, cardio-embolic cause 12 lead ECG series , may identify PAF Look for postural hypotension 24 hour tape Echo (TTE)

42. Who to investigate for PFO? Class I Any age visceral or peripheral embolism <45 CVA >45 CVA without risk factors for CVD Any age if decision re anticoagulation may change Class IIa Any age CVA with possible embolic cause

43. What do we need to know? How do we diagnose it? Is there a risk associated with PFO? Will the risk be reduced by medical therapy? Will the risk be reduced by closure? Is closure safe?

44. Incidence Autopsy study: n=965 PFO 27% 34% <30 20% >80 3.4mm 5.8mm Echocardiographic surveillance studies PFO 8% (2-23%) ASA 7.1% (3-12%) MVP 8.9% (5-9%)

45. Diagnosis TransCranial Doppler 86% Transthoracic Echo and contrast >90% TOE and contrast >90% Two modalities are better than one

50. The risk of PFO and stroke Lechat et al age<55 CVA Control PFO 10% All CVA PFO 40% (p<0.001) Cryptogenic PFO 54% Mas et al age 18-35 CVA All CVA PFO 36% Lechat n=60Lechat n=60

51. Meta-analysis CVA <55 9 studies PFO OR 3.1 (2.3-4.2) ASA OR 6.1 (2.5-15) Both OR 15.6 (2.8-86)

52. What do we need to know? How do we diagnose it? + Is there a risk associated with PFO? + Will the risk be reduced by medical therapy? Will the risk be reduced by closure? Is closure safe?

53. Mechanism? Paradoxical embolism? Larger hole found in CVA pts vs non-CVA Residual shunt after closure predicts recurrence Divers brains and PFO In situ clot in tract? Predict atrial arrhythmias? (OR 4.1) Predict a hypercoagulable state?

54. Medical Therapy What? Aspirin or Warfarin Comess et al n=33 16% pa No Rx Mas et al n=132 3.4% pa Aspirin or warfarin Lausanne registry 3.8% pa Aspirin or warfarin

55. Device closure Meier et al CVA/TIA 6.6% pa No Closure 4.5% pa Closure Stroke risk 3% No Closure 0% Closure RCT awaited

56. What do we need to know? How do we diagnose it? + Is there a risk associated with PFO? + Will the risk be reduced by medical therapy? + Will the risk be reduced by closure? ? Is closure safe?

59. Who to investigate? Class I Any age visceral or peripheral embolism <45 CVA >45 CVA without risk factors for CVD Any age if decision re anticoagulation may change Class IIa Any age CVA with possible embolic cause

60. Problems Failure to deploy <5% Device embolisation 1% Thrombus 1-5% Death 0% I quote 1% risk from procedure

61. What do we need to know? How do we diagnose it? + Is there a risk associated with PFO? + Will the risk be reduced by medical therapy? + Will the risk be reduced by closure? ? Is closure safe? +

62. Who to Close? None? All? I like balanceI like balance

63. Conclusion Closure may well reduce the risk of recurrence and should be considered within 3 months Divers and those with Migraine deserve special consideration also

64. Conclusions Investigation and treatment essential Strokes time as a “cinderella” is over Worthwhile interventions are available (at a price) These are worthless without stopping smoking, lipids, BP control etc.

66. Case 1 59 year old Loss of speech and weakness in right hand for 1 hour No HT/DM/smoking/FH/Lipids/Renal No cardiac symptoms MRI confirms stroke Carotids OK

67. Case 1 Needs cardiac work-up to exclude PAF LAA clot PFO PFO found with large shunt. Close it?

68. Case 2 52 year old One clinical episode of weakness in L arm No risk factors MRI shows 5 areas of infarction of similar age on left side Carotids OK bilaterally

69. Case 2 Needs investigation for: PAF LAA clot PFO PFO found Should close this!

70. Case 3 68 yr old Asian/HT/DM/IHD with CABG Recurrent TIAs with left sided weakness Carotids bilateral >80% stenosis

72. Case 3 Need to exclude PFO, PAF? Need to treat R carotid urgently CEA CAS