UPDATE ON STROKE IN OLDER PEOPLE: CLINICAL CASES IN EVERYDAY PRACTICE

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1 UPDATE ON STROKE IN OLDER PEOPLE: CLINICAL CASES IN EVERYDAY PRACTICE Joseph SK Kwan Clinical Associate Professor, HKU Honorary Consultant, Queen Mary Hospital & Grantham Hospital

2 CASE: 82 YEAR OLD LADY Sudden R weakness affecting face and leg 1 h ago Dysphasia, hemianopia, NIHSS 15 History of DM, HT, CAD Meds: Amlodipine, Glipizide, Aspirin BP 175/90, P90, afebrile ECG: AF, Bloods: glucose 13 Improved and almost back to normal after 3 h CTB: mild atrophy only, small vessel disease

3 CASE: 82 YEAR OLD LADY What is the diagnosis? What would you do next?

4 CT SIGNS OF EARLY INFARCTION

5 ANATOMY

6 HYPOATTENUATION

7 GREY-WHITE DIFFERENTIATION

8 LENTIFORM NUCLEUS & INSULAR RIBBON

9 SULCAL EFFACEMENT

10 CYTOTOXIC (NOT VASOGENIC) OEDEMA At 4 hours 1 day later

11 HAEMORRHAGIC TRANSFORMATION

12 ENCEPHALOMALACIA, HYDROCEPHALUS EX-VACUO

13 HAEMORRHAGE

14 CASE: 82 YEAR OLD LADY Sudden R weakness affecting face and leg 1 h ago Dysphasia, hemianopia, NIHSS 15 History of DM, HT, CAD Meds: Amlodipine, Glipizide, Aspirin BP 175/90, P90, afebrile ECG: AF, Bloods: glucose 13 Improved and almost back to normal after 3 h MRI: DWI lesion showing new infarct L frontal lobe

15 CASE: 82 YEAR OLD LADY What is the diagnosis? What would you do differently?

16 WHAT IS A TIA? Traditional time-based definition: Focal neurological symptoms of ischemic cause that last <24 hours The old time-based criterion was arbitrarily chosen, based on the belief that brain parenchyma may not be permanently damaged Miller Fisher at the nd Princeton Cerebrovascular Conference

17 MRI IN TIA FLAIR Rovira Am J Neurorad 2002;23:77 a) DWI b) ADC c) MTT d) FLAIR e) GRE f) MRA

18 CASE: 82 YEAR OLD LADY Sudden R weakness affecting face and leg 1 h ago Dysphasia, hemianopia, NIHSS 15 History of DM, HT, CAD Meds: Amlodipine, Glipizide, Aspirin BP 175/90, P90, afebrile ECG: AF, Bloods: glucose 13 Improved and almost back to normal after 3 h MRA: occluded L M1 with fresh clot causing low perfusion, but DWI normal (<3 h)

19 CASE: 82 YEAR OLD LADY What is the diagnosis now? What would you do differently?

20 ACUTE TREATMENT Stroke unit care?severity,?integrated vs. acute unit Immediate Aspirin?dose,?duration,?change to Clopidogrel,??dual vs. single IV rt-pa Europe <3 h all ages, h for <80 yr USA no upper age limit, not FDA approved for >3 h Pan et al. J Stroke Cerebrovasc Dis 2013;22:690

21 RT-PA: NNT TIMING NNT = 2 NNT = 4 NNT = 8 NNT = 14

22 IST-3 Randomised 3035 pts, 53% >80 years Control Rt-PA Rt-PA Control

23 IST-3 Randomised 3035 pts, 53% >80 years Control Rt-PA Rt-PA Control

24 RT-PA BENEFIT FOR >80 YEARS For every 1000 older patients treated <3 h, there are 95 more alive and independent at the end of follow up Symptomatic ICH not higher in older people (OR 1.3 CI )?lower dosage for Asians e.g. 0.9mg/kg max 50mg (Pan et al 2013) Curr Opinion in Neurol 2014;27:8

25 Cerebrovas Dis 2013;36:161

26 REVASCULARISATION Revascularization includes 3 separate concepts: Recanalization = arterial patency Reperfusion = antegrade microvascular perfusion Collateralization = microvascular perfusion via pial arteries or other anastomotic arterial channels that bypass the primary site of vessel occlusion

27 WAKE UP STROKES 1:4 strokes occur in sleep Many wake-up strokes occur close to awakening Neuroimaging approaches may identify wake-up stroke patients likely to benefit from thrombolysis e.g. non-contrast CT, CT-perfusion, penumbral MRI, and diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR). Small case series and observational studies report results of thrombolysis in wake-up stroke, with no safety concerns, but no conclusion on efficacy can drawn. Ongoing clinical trials are enrolling wake-up stroke patients based on neuroimaging findings: DWI-FLAIR-mismatch (WAKE-UP) and penumbral imaging (EXTEND).

28 MISMATCH DWI represents infarct core, PWI identifies the area of critically hypoperfused tissue Lack of cerebral blood flow with decreased intracellular energy metabolism causes cytotoxic edema, which can be detected by a reduced apparent diffusion coefficient (ADC) on DWI within minutes of stroke. During the following 1 4 h, tissue osmolality increases, accompanied by a net increase of water. This absolute increase of water content can be detected by T2-weighted or FLAIR Front Neurol 2014;5:1

29 CASE: 82 YEAR OLD LADY Sudden R weakness affecting face and leg 1 h ago Dysphasia, hemianopia, NIHSS 15 History of DM, HT, CAD Meds: Amlodipine, Glipizide, Aspirin BP 175/90, P90, afebrile ECG: AF, Bloods: glucose 13 Improved and almost back to normal after 3 h MRI: DWI showed 3 new infarcts in L frontal, R occipital, and brainstem

30 CASE: 82 YEAR OLD LADY What is the diagnosis now? What would you do differently?

31 RX TIME WINDOW FOR TIA 1 week Of those who will go on to develop a stroke <3 months, the vast majority will do so within the first week Investigating and treating high risk TIAs can reduce risk of subsequent stroke by 80% (EXPRESS) Lancet Neurol 2009;8:235; BMJ 2004;328:326

32 Stroke risk reductions from randomized trials of antithrombotic agents in atrial fibrillation. Granger C B, and Armaganijan L V Circulation. 2012;125:

33 CHANCE STUDY Randomized, double-blind, multicenter, placebo-controlled trial at 114 centers in China Randomised <24 hours of minor stroke (NIHSS <4) or TIA (ABCD >3) For first 21 days, randomized to a) Group 1 with Clopidogrel (300 mg loading then 75 mg od) + Aspirin ( mg loading dose then 75 mg od), or b) Group 2 with Aspirin alone ( mg loading dose then 75 mg od). Between 21 days and 3 months, patients in Groups 1 and 2 were respectively treated with Clopidogrel (75 mg od) alone or Aspirin (75 mg od) alone. Primary outcome was all stroke at 90 days of follow-up in an intention-to-treat analysis. NEJM 2013;369:11

34 CHANCE STUDY Randomized, double-blind, multicenter, placebo-controlled trial at 114 centers in China Randomised <24 hours of minor stroke (NIHSS <4) or TIA (ABCD >3) For first 21 days, randomized to a) Group 1 with Clopidogrel (300 mg loading then 75 mg od) + Aspirin ( mg loading dose then 75 mg od), or b) Group 2 with Aspirin alone ( mg loading dose then 75 mg od). Between 21 days and 3 months, patients in Groups 1 and 2 were respectively treated with Clopidogrel (75 mg od) alone or Aspirin (75 mg od) alone. Primary outcome was all stroke at 90 days of follow-up in an intention-to-treat analysis. Mean age = 62 (IQR 55-72) NEJM 2013;369:11

35 DAPT Risk of stroke recurrence in dual vs mono APT for patients with AIS or TIA Circulation 2013;128:1656

36 DAPT: MAJOR BLEEDING Circulation 2013;128:1656

37 NOAC Am J Medicine: Anticoagulation in the Post-Warfarin Era: Where Are We Today?

38 NOAC Am J Medicine: Anticoagulation in the Post-Warfarin Era: Where Are We Today?

39

40 NOAC

41 NOAC IN OLDER PEOPLE Frail elderly people not represented in NOAC trials Only <1/3 patients randomized were >75 years old Subgroup analysis = elderly might have a higher risk of extra-cranial bleeding (vs. Warfarin) High risk of renal impairment / deterioration Drug-drug interactions less known Not easily monitored No antidote Dysphagia Use of TCM J Stroke 2014;16:73; Drug Aging 2013;30:949

42 CASE: 82 YEAR OLD LADY 1 month later, admitted w chest pain, raised TNI 0.4, LAD lesion 90% Cardiologist wishes to perform PCI Consults Geri for advice for long term AC BP 160/90, On Warfarin, INR 1.9 What will be your advice?

43 BLEEDING RISK SCORES Comparison of predictive performance of bleeding risk-estimation tools in cohort of patients with AF undergoing PCI in a multicenter European prospective registry. HAS-BLED, ATRIA, mobri, and REACH bleeding risk-prediction scores and assessed the rate of bleeding complications as defined by Bleeding Academic Research Consortium at 12 months follow-up in 929 consecutive patients undergoing PCI. Higher bleeding in a) older patients, b) history of peptic ulcer disease Mean age 74 (11) Am J Cardiol 2014;113:1995

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45 VKA + APT Study of 8700 patients with mean age 74.2 years Conclusion In AF + stable CAD, addition of APT to VKA has no additional benefit on recurrent coronary events or thromboembolism (incl. stroke), whereas bleeding risk is increased significantly. Circulation 2014;129:1577

46 VKA + APT Study of 8700 patients with mean age 74.2 years Conclusion In AF + stable CAD, addition of APT to VKA has no additional benefit on recurrent coronary events or thromboembolism (incl. stroke), whereas bleeding risk is increased significantly. Older people??12-15% Circulation 2014;129:1577

47 NOAC BETTER FOR ASIANS? RELY = RCT of Dabigatran vs. Warfarin in 2782 patients Stroke rate on W is higher in Asians (3.06%) than non-asians (1.48%) TTR is lower in Asians Hemorrhagic stroke on warfarin occurred more often in Asians than non-asians (HR 2.4; CI ; P=0.007) Reductions in ICH with D may be greater for Asians (D110 vs. W = HR 0.15, D150 vs. W = HR 0.22) than non-asians (D110 vs. W = HR 0.37, D150 vs. W = HR 0.28) Major bleeding rates in Asians were significantly lower on D (both doses) than W (W = 3.82% per year, D110 = 2.22% per year, and D150 = 2.17% per year). Stroke 2013;44:1891

48 CVA ON W = HIGHER, BENEFIT = GREATER Stroke 2013;44:1891

49 BLEED ON W = HIGHER, BENEFIT = GREATER Stroke 2013;44:1891

50 CASE: 82 YEAR OLD LADY Readmitted w acute delirium over 3 days Fell w head injury Hallucination, aggressive Swallow unsafe, no new neurology On Dabigatran + Aspirin BP 170/80 ECG: AF, Bloods/Urine: normal CT: old infarct w new area of infarction and petechial haemorrhage R parietal

51 CASE: 82 YEAR OLD LADY What is the diagnosis? What would you do next?

52 WHEN TO RESTART ANTICOAGULANT Assess competing risks of haematoma growth, recurrent ICH and thromboembolic events Lobar haemorrhage or cerebral amyloid angiopathy = ICH recurrence > thromboembolic risk from AF = stop AC Deep + small ICH + baseline risk of ischemic stroke >6.5% per year (CHADS2 4 or CHA2DS2-VASc 5) = restart AC Time to resumption of AC >10 weeks Thromb Haemost 2014;111:14

53 SEIZURES AFTER STROKE Can be difficult to distinguish post-ictal vs. new stroke vs. both Rt-PA contraindication only if pre-stroke seizure Can present with delirium, LOC, falls Usually responsive to AED First line = Na Valproate, Lamotrigine Second line = Levitiracetam Third line = Gabapentin Avoid Carbamazepine, Phenytoin Zero order pharmacokinetics = PHT, W, A, Alcohol, Theophylline