When Not To Give TPA Steve Phillips Division of Neurology

Transcription

1 When Not To Give TPA Steve Phillips Division of Neurology

2 AstraZeneca Disclosures - 1 I have given CME lectures and served on advisory boards for Boehringer Ingelheim Bristol-Myers Squibb Hoffmann-LaRoche Merck Frosst Pfizer sanofi-aventis Servier The QEII Acute Stroke Program has received support from GlaxoWellcome, Hoffmann-La Roche, Merck Frosst, sanofi-aventis, Servier, Bayer

3 Disclosures - 2 I was Canadian coordinator for the third International Stroke Trial of t-pa (IST-3) I am a Clinical Advisor for Cardiovascular Health Nova Scotia (CVHNS) I was inaugural co-chair of the Best Practices & Standards Advisory Committee of the Canadian Stroke Strategy

4 Give em the juice! Michael Hill, MD

5 IV t-pa works for A broad spectrum treatment mild, moderate, and severe strokes men and women Stroke Thrombolysis Trialists Collaborative Group, 2014 & 2018

6 Treatment and outcome IV thrombolysis within 6 h of AMI* - alive 35 days later Benefit N / 1000 treated 30 *Fibrinolytic Therapy Trialists' Collaborative Group. Lancet. 1994; 343:

7 Treatment and outcome IV thrombolysis within 6 h of AMI* - alive 35 days later IV tpa within 6 h of stroke^ - alive & independent months later Benefit N / 1000 treated *Fibrinolytic Therapy Trialists' Collaborative Group. Lancet. 1994; 343: ^Emberson J, et al. Lancet. 2014; 384:

8 Treatment and outcome IV thrombolysis within 6 h of AMI* - alive 35 days later IV tpa within 6 h of stroke^ - alive & independent months later IV tpa within 3 h of stroke^ - alive & independent months later Benefit N / 1000 treated *Fibrinolytic Therapy Trialists' Collaborative Group. Lancet. 1994; 343: ^Emberson J, et al. Lancet. 2014; 384:

9 Odds Ratio (95% CI) Effect of timing of IV t-pa on good outcome (mrs 0-1) Treatment delay (h) Emberson, et al. Lancet 2014; 384:

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11 Life is short; and the art long; and the right time an instant; and treatment precarious; and the crisis grievous. Hippocrates (translator Dickinson Richards)

12 TPA is chemical neurosurgery

13 A case from the Annals of the QEII Emergency Department

14 74 year-old woman 10:00 h sudden left arm weakness & slurred speech One month earlier had transient left leg weakness & found to be in AF. Declined anticoagulant therapy Cognitively intact & functionally independent (CIFI) T+33 mins 911 Pre-hospital Acute Stroke Protocol activation T+46 mins triaged into ED

15 74 year-old woman BP 190/100; AF on ECG Alert Dysarthric Visual fields full Left facial droop, arm paralyzed, leg drift No sensory loss or neglect

16 Diagnosis Probable ischemic stroke Localization: Syndrome: Severity: Mechanism: Prognosis: Anterior right hemisphere Partial MCA Moderate (NIHSS=8) Probable cardiogenic embolism 45% probability of death or dependency at 1 year

17 Multimodal CT imaging at T+90 mins Non-contrast CT head

18 Time-to-Peak Cerebral Blood Flow Cerebral Blood Volume

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20 Labetalol 10 mg IV x2 BP 170/90 PLT 250, INR 1.0 Consent discussion; 7-10% bleeding risk

21 Consent issues US guidelines recommend obtaining informed consent when feasible Canadian Best Practice Recommendations 2018: TPA is considered standard of care. Routine procedures for emergency consent apply. Obtaining consent delays treatment

22 In cases of medical emergency when the patient (or substitute decision maker) is unable to consent, a physician has the duty to do what is immediately necessary without consent.

23 a contemporaneous record (at the time) should be made explaining the circumstances which forced the physician's hand.

24 And If you don t treat, document why and explain to the patient s family

25 ED physicians more often sued for not giving tpa for stroke Liang BA, Zivin JA. Empirical characteristics of litigation involving tissue plasminogen activator and ischemic stroke. Ann Emerg Med. 2008; 52:

26 This is not America

27 or

28 Labetalol 10 mg IV x2 BP 170/90 PLT 250, INR 1.0 Consent discussion; 7-10% bleeding risk TPA started 2 h 20 m after stroke onset

29 Labetalol 10 mg IV x2 BP 170/90 PLT 250, INR 1.0 Consent discussion; 7-10% bleeding risk TPA started 2 h 20 m after stroke onset ~1 hour later: BP 180/100, mute, right gaze preference

30 NCCT 80 mins after start of t-pa Patient deceased 7 hours after stroke onset

31 Predicting brain hemorrhage after t-pa

32 age BP blood glucose creatinine prior antiplatelets stroke severity visible infarct on CT cerebral microbleeds very low cerebral blood volume Karaszewski B, et al. J Neurol Neurosurg Psychiatry 2015; 86:

33 first released December 2006 continuously updated since

34 Acute Ischemic Stroke Treatment Update 5.3.i All eligible patients with disabling ischemic stroke should be offered IV t-pa. Eligible patients are those who can receive treatment within 4.5 hours of stroke onset. [Evidence Level A]

35 Acute Ischemic Stroke Treatment Update 5.3.ii All eligible patients should receive IV t-pa as soon as possible after hospital arrival. [Evidence Level A] Target door-to-needle time <60 min in 90% of treated patients & median 30 min. [Evidence Level B]

36 Update 2018 Thrombolytic Therapy Inclusion Criteria Age >18 <4.5 h since onset (or LSN) Absolute Exclusion Criteria Intracranial hemorrhage (ICH) At risk of major extracranial hemorrhage

37 Update 2018 Thrombolytic Therapy Patients on a Direct Oral Anticoagulant IV t-pa should not be routinely administered In centers with access to specialized tests of DOAC levels and reversal agents, IV t-pa could be considered

38 Update 2018 Thrombolytic Therapy Relative Exclusion Criteria History of ICH Stroke or head trauma in prior 3 months Major surgery in prior 14 days Arterial puncture in prior 7 days Refractory hypertension >180/105

39 Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) PI: Craig Anderson, The George Institute for Global Health, Australia P: Ischemic stroke, <4.5 hours, SBP>140 I: 1. Intensive BP lowering (SBP ) 2. tpa low dose (0.6 mg/kg) C:1. Guideline BP lowering (SBP <180) 2. tpa normal dose O: mrs N: Target 4,800

40 Update 2018 Thrombolytic Therapy Relative Exclusion Criteria Blood glucose <2.7 or >22.2 INR >1.7 PTT PLT <100 ASPECTS <6

41 Alberta Stroke Program Early CT Score Examine all the images at the ganglionic and supra-ganglionic levels Take off 1 pt from 10 for every region affected 8-10 Small core 6-7 Moderate core 0-5 Large core aspectsinstroke.com

42 Stroke Thrombolysis in Nova Scotia

43 Stroke Thrombolysis in Nova Scotia 2004/05* 2015^ Ischemic stroke patients Treated with t-pa 3% 13% Arrived in time & treated 11% 40% Median door-to-needle 93 min 68 min *Provincial Stroke Audit ^CVHNS Provincial Stroke Registry

44 Bleeding Complications sich Nova Scotia 2015 (n=183) 8%* sich=symptomatic intracranial hemorrhage *CT confirmed or death within 48 h post-tpa

45 Bleeding Complications sich mech Nova Scotia 2015 (n=183) 8% Systematic Review 2012 (n=3548) 8% IST-3 (n=1515) 7% 1% SITS Registry (n=6483) 7% sich=symptomatic intracranial hemorrhage; mech=major extracranial hemorrhage

46 Update 2018 Thrombolytic Therapy Treatment of Bleeding Complications Insufficient evidence to support use of: cryoprecipitate or fresh-frozen plasma prothrombin complex concentrate platelet transfusion tranexamic acid

47 When Would I Not Treat? Very mild stroke causing non-impairing deficit Very severe stroke in the frail elderly or terminally ill

48 What Do We Do?

49 Insights from 1. Patients who arrive in time but are not thrombolysed 2. Patients whose treatment is complicated by brain hemorrhage Data from QEII Acute Stroke Registry

50 Acute Ischemic Strokes Admitted Through QEII Emergency Department Total N TPA 73 (28%) 66 (25%) 52 (23%) 191 (26%)

51 Acute Ischemic Strokes Admitted Through QEII Emergency Department Arrived <3.5 h but no TPA Total N TPA 73 (28%) 66 (25%) 52 (23%) 191 (26%) 57 (22%) 51 (19%) 50 (22%) 158 (21%)

52 Lysed cf Not- lysed (1/3) TPA No TPA TPA No TPA TPA No TPA Age % men % living at home % living alone

53 Lysed cf Not- lysed (1/3) TPA No TPA TPA No TPA TPA No TPA Age % men % living at home % living alone Untreated patients older

54 Lysed cf Not- lysed (2/3) % Prior: TPA No TPA TPA No TPA TPA No TPA stroke cognition dependency

55 Lysed cf Not- lysed (2/3) % Prior: TPA No TPA TPA No TPA TPA No TPA stroke cognition dependency Untreated patients older; and more likely to have prior stroke, cognitive and functional impairment

56 Lysed cf Not- lysed (3/3) TPA No TPA TPA No TPA TPA No TPA % ASP activated % Mild stroke % Moderate stroke % Severe stroke

57 Lysed cf Not- lysed (3/3) TPA No TPA TPA No TPA TPA No TPA % ASP activated % Mild stroke % Moderate stroke % Severe stroke Untreated patients older; more likely to have prior stroke, cognitive and functional impairment, and mild stroke; and less likely to be code strokes

58 Intracerebral hemorrhage after TPA at the HI

59 Intracerebral hemorrhage after TPA at the HI Total TPA [no EVT] ICH, n (%) 3 (4.8) 1 (1.9) 4 (10) 8 (5.2)

60 TPA [No EVT] ICH No ICH n=8 n=148 Age (median) % men % prior stroke % prior cognition % prior dependency Bleeders more likely to cognitively impaired, dependent

61 TPA [No EVT] ICH No ICH n=8 n=148 LSN to TPA (median mins) % AF % mild stroke 0 5 % moderate stroke % severe stroke Bleeders more likely to cognitively impaired, dependent, in AF

62 TPA [No EVT] ICH No ICH Stroke syndrome n=8 n=148 % MCA % Lacunar Bleeders more likely to cognitively impaired, dependent, in AF, with a lacunar stroke

63 TPA [No EVT] ICH No ICH n=8 n=148 % death in hospital % survivors dependent at discharge 80 51

64 Last slide No useful clinical tool to predict who will bleed after t-pa Guidelines are helpful! Mild strokes are difficult! Frailty, comorbidity, impaired cognition, and functional dependency may be reasons not to treat There are worse things than dying from a severe stroke

65 Thanks!

66 Symptomatic intracranial hemorrhage in systematic review of stroke t-pa trials Treated within 3 h All 5 trials before IST-3 IST-3 All 6 trials (n=1779) Treated between 3 to 6 h OR 4.6 ( ) All 6 trials before IST-3 IST-3 All 7 trials (n=4965) OR 3.7 ( ) Lancet 2012; 379:

67 Update 2018 Thrombolytic Therapy Treatment of tpa-induced Angioedema Stop t-pa Airway management Hydrocortisone 100 mg IV Diphenhydramine 50 mg IV Ranitidine 50 mg IV [risk of BP and ICH with nebulized epinephrine]

68 Door to Image/Needle (minutes) Number of patients Stroke Thrombolysis in Nova Scotia N, Door-to-CT & Door-to-Needle Times (median, IQR) Calendar Year 0 Number treated 0-3hrs from symptom onset Median door to image Number treated >3hrs from symptom onset Median door to needle

69 Stroke Thrombolysis in Helsinki Meretoja A, et al. Neurology. 2012; 79:

70 Content Give em the juice Summary of trial data (Emberson paper; Lees ESOC presentation) mild, moderate and severe strokes benefit timing difficulty predicting ICH (Will Whiteley) Canadian Stroke Best Practice Recommendations Local data ischemic stroke patients who arrive in time but are not treated treated patients who bled CVHNS data on bleeding Thrombolysis in the EVT era (TNK_mdhEditorial2018)