Stroke Therapeutics Flashcards
What is included in the general supportive care for stroke (5)
Pyrexia – treat high temperature
O2 – if low
Rehab – as soon as patient is stable
NPO – if LOC and swallow test
Family and community support for social reintegration
How to prevent DVT in stroke patients
- Early mobilization
- Adequate hydration
- Intermittent pneumatic compression strocking within first 24hr
- Use UFH or LWMH prophylactic doses with ischemic stroke who cannot move one or both lower limbs
**STOP if OAC is ordered
What is the inclusion criteria for thrombolytics
All need to be present (6)
- Ischemic stroke
- NHISS score 4+ (means stroke is disabling)
- Prior status (see if they were already disabled before)
- Life expectancy of 3+ months
- Age 18+
- ONSET OF STROKE <4.5 hours
T/F Age under 18 is a contraindication for thrombolytics in stroke patients
False
What are absolute contraindications to thrombolytics
Active hemorrhage
Any condition that can increase risk of major bleeding
What is the altepase dosing?
0.9mg/kg over 1 hour
then 10% of the dose given as bolus over 1 min
What is the target BP (SBP & DBP) for administering altepase?
What do you do if it is higher?
Target is SBP <180 or DBP <105
If higher
- administer IV labetolol (10-20mg), nicardipine (5), clevidipine, hydralazine, enalapril
How often do you monitor for BP and nuero assessments during altepase administration
First 2 hours: q15 min
Next 6 hours: q30 min
24 hours after: q1 hour until finished
What follow up monitoring/investigations do you have you to do 24 hours after altepase?
CT or MRI scan before starting OAC or antiplatelet
What are risks of administering altepase at high BP? (2)
- Life-threatening ICH (suspected when patient has sudden deterioration of neurological status -> order CT scan STAT)
- Orolingual/hemi-lingual angioedema (acute welling of tongue/lips/face): Occurs in 5% of tPA patients, very serious, requires continuous monitoring
(Treatment: tPA to be stopped immediately -> IV corticosteroids, H2RAs, diphenhydramine)
What do the trials say for altepase efficacy when given in these hours:
Within 3 hours
Between 3-4.5 hours
Between 4.5-6.3 hours
Thrombolysis within 3 hours increased chances of being alive and more functional 3-6 months after ischemic stroke.
Thrombolysis within 4.5 hours still had benefit, but not as great.
Thrombolysis within 6.3 hours had no difference in outcomes.
These benefits are consistent even if <80 or >80.
T/F thrombolytics saves lives
False
- goal is to reduce effects on QOL after the stroke
What is the BP target for patients not eligible for thrombolysis?
BP target <220/120 mmhg
what factors MAY increase mortality from thrombolysis? (5)
- Being older
- a woman
- non-Hispanic white race
- A fib
- higher NIHSS
Who should still get altepase if 4.5 hours has passed?
Who was excluded?
WAKE-UP trial
EXTEND trial
WAKE-UP
- >4.5 hours after onset of symptoms who had SPECIAL IMAGING to determine eligibility
EXTEND
- 4.5-9 hours after onset of symptoms who had ADVANCED IMAGING to determine eligibility
Excluded
- ICH
- Planned EVT
- NIHSS >25
What is the difference between tenecteplase and altepase?
Dose?
Efficacy
Safety
Main advantage of Tenecteplase: One single bolus dose (vs 1 hour infusion of Alteplase)
Non-inferior in efficacy and safety
Dose = 0.25mg/kg (max 25 mg dose)
For acute treatment of stroke who should get antiplatelet agents?
When?
Dose?
All patients with ischemic stroke or transient ischemic attack
- AFTER imaging (MRI/CT) EXLUDES intracranial hemorrhage
- within 24 hours of symptoms onset (ideally within 12)
Dose: 160mg
- no need to load if on it daily
T/F avoid ASA for patients receiving thrombolysis therapy in the first 24 hours
True
How do you administer ASA for patients with dysphagia? (2)
Enteral tube
Rectal suppository (325mg)
Who should get antiplatelet therapy in secondary prevention?
When?
Dose?
all patients with acute ischemic stroke/TIA unless they are on an anticoagulant
When
- AFTER imaging (MRI/CT) EXLUDES intracranial hemorrhage
- within 24 hours of symptoms onset (ideally within 12)
Dose:
- ASA 81mg
- Clopidogrel 75mg
- ASA/Dipyridamole (aggrenox) 25mg/200mg BID (not for patients with dysphagia)
What do the 7 trials say about efficacy for ASA in the acute phase?
Non-fatal stroke recurrence
Vascular death
All-cause mortality
Reduction in all:
Non-fatal stroke recurrence: Sig
Vascular death: non-Sig
All-cause mortality: non-Sig
Despite insignificance, the trend points towards benefit of ASA for all 3 outcomes
What do the 21 trials say about efficacy for ASA in the secondary prevention?
Non-fatal stroke recurrence
Vascular death
All-cause mortality
Non-fatal stroke recurrence
Vascular death
All-cause mortality
- All signifcant
Do benefits outweigh the harms of using ASA in ischemic stroke?
CAST and IST trial
CAST trial (160mg ASA vs placebo) + IST trial (300mg ASA vs UFH):
- significant reduction in recurrent ischemic stroke (ARR 0.7%)
- insignificant reduction in death without stroke
Safety:
- insignificant increase in hemorrhagic stroke
Bottom line: significant benefits + insignificant harms of ASA
What is the dose range you can give for ASA according to the ATC trial
75-235mg daily
What does the CAPRIE trial tell us in clopidogrel vs ASA?
No benefit of clopidogrel over ASA for stroke
- only benefit in PAD patients
Typically used if ASA intolerant or already on ASA prior to stroke
What did the CHANCE trial and POINT trial tell us about loading dose of clopidogrel?
CHANCE
- use 300mg loading dose
POINT
- use 600mg loading dose
Use depending on risk vs benefit
What does the ESPRIT trial tell us about Aggrenox vs ASA in:
Primary outcome (vascular death + stroke + MI + beeding)
Major bleeding
Dropout rate
Primary outcome (vascular death + stroke + MI + beeding)
- BETTER than ASA (significant)
Major bleeding
- similar (insignificant)
Dropout rate
- much higher in Aggrenox (34%)
- Lots of ADRs, majority are headaches, BID regimen
Who should get DAPT? (3)
- High risk of TIA ABCD2 score 4+
- NIHSS score 0-3
- Not at high bleed risk
What DAPT should they get?
For how long?
Clopidogrel 75mg (LD 300mg or 600mg) and ASA 81mg
21 days
When should you give DAPT longer than 21 days?
Specific indication
- arterial stent
- symptomatic intracranial artery stenosis
What is the other option for DAPT for 30 days?
Ticagrelor + ASA for 30 days
What does the MATCH trial say about adding ASA in high risk patients with 1 risk factor already taking clopidogrel 75 daily
No difference in reducing [stroke + MI + CV death + rehospitalization] but DAPT (ASA + clopidogrel) caused more bleed
What were the exclusion criteria for the CHANCE and POINT trial (5)
Excluded patients
- IV thrombolysis
- EVT
- ICH
- mod-severe strokes (4+ NIHSS)
- patients on anticoagulation for any reason
What did the CHANCE and POINT trial comparecompare
CHANCE
- Day 1-21: 75mg (LD 300mg clopidogrel) + (75-300mg ASA)
- Day 22-90: Clopidogrel + placebo
VS
- ASA + placebo
POINT
- Day 1-90: Clopidogrel (LD 600) + ASA
VS
- ASA + placebo
What were the results of the CHANCE and POINT trial
What days had most benefits
main benefit of DAPT occurs in first 21 days (with bleed risk increasing very slightly overall)
- most benefit in the first 7-10 days
What did the THALES trial tell us about ticagrelor (90mg BID) 30 days + ASA compared to
Sig reduction in future stroke risk, however significant increase in bleed risk
If patient has an indication for OAC, when do we restart it after?
Is this evidence based?
What do you bridge with in the meantime?
1-3-6-12 day rules
1: TIA, start after 1 day
3: Mild stroke (NIHSS <4)
6: Moderate stroke
12: Severe stroke
What do you bridge with in the meantime?
- ASA
What did the ENCHANTED trial say for BP target before giving altepase
SBP 130-140 vs 180
SBP 130-140 vs 180
- no difference
T/F SPRINT trial applies to stroke patients
False
What is BP tagrget for
Subcortical stroke
Ischemic stroke/TIA
Subcortical stroke: <130
Ischemic stroke/TIA: 140/90
What did the PROGRESS Trial say with perindopril vs perindopril + indapamide for reducing stroke + major vascular events
perindopril + indapamide was more effective
What did the PROGRESS-POST HOC ANALYSIS say with perindopril vs perindopril + indapamide for reducing stroke + major vascular events
Stroke risk is based on SBP, does not matter what agent is used
What is the target LDL for stroke patients?
LDL <1.8 mmol/L
- Treat-to-target LDL is used in stroke
Who should not get a statin?
Post-intracerebral hemorrhage
Which type of statin should be used for stroke patients.
What if LDL levels not met?
INTERMEDIATE intensity statin (no higher, to reduce risk of ADRs)
If LDL <1.8mmol/L is not met, ezetimibe, PCSK9 OR Icosapent can be ADDED on to statin
What does the SPARCL trial say about who to not use Atorva 80 (high-intensity statin) (3)
- Had hemorhagic stroke at baseline
- Older men/women
- High BP (SBP 160+ or DBP 100+)
Which 2 diabetic agents have CV benefit
SGLT2is
GLP-1RAs
Physical activity recommendation in stroke patients
Moderate-vig intensity for 10-20 min 2-4 times/week
if possible
- 40 min 4 times/week
What is the foundation of intracerebral hemorrhage treatments (2)
Anticoagulant reversal
Blood pressure control
What do you administer if warfarin was used in the last 1-2 hours
Charcoal
Reversal agents
Warfarin (3)
dabigatran
Apixiban, edoxaban, rivaroxaban
Warfarin
- vit K, prothrombin, fresh-frozen plasma
dabigatran
- idarucizumab
Apixiban, edoxaban, rivaroxaban
- andexanet alfa
What is BP target in hemorrhagic stroke?
First 6 hours <160
<130/80
