a stroke of knowledge: cerebrovascular accidents
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A Stroke of Knowledge:
Cerebrovascular Accidents/
Transient Ischemic Attack (CVA/TIA)
Shayna Cruz, BS, PharmD Candidate 2019
Heather Powell, PharmD, BCPS
Shayna Cruz and Heather Powell declare no
conflicts of interest, real or apparent, and no
financial interests in any company, product, or
service mentioned in this program, including
grants, employment, gifts, stock holdings and
honoraria.
Disclosures and Conflict of Interest
At the conclusion of the program, the pharmacists will be able to:
1. Describe the risk factors, pathophysiology, and epidemiology of
cerebrovascular accidents (CVA)/transient ischemic attacks
(TIA).
2. Identify pertinent signs and symptoms of a patient who may be
experiencing a CVA/TIA.
3. Describe non-pharmacologic and pharmacologic treatment
regimens for the primary and/or secondary prevention of
CVA/TIA.
4. Compare and contrast antiplatelet therapies for secondary
ischemic stroke prevention.
5. Discuss newly published trials and stroke guidelines
Pharmacist Objectives
At the conclusion of this program, the pharmacy technician will
be able to:
1. Describe the risk factors, pathophysiology, and epidemiology of
cerebrovascular accidents (CVA)/transient ischemic attacks
(TIA).
2. Identify pertinent signs and symptoms of a patient who may be
experiencing a CVA/TIA.
Technician Objectives
Which of the following is/are modifiable risk factors
for CVA/TIA ? Select ALL that apply.
a) Diabetes
b) Hypertension
c) Cigarette smoking
d) Obesity
Pre-Test Question 1
What is the recommended duration of treatment
for dual antiplatelet therapy (aspirin and
clopidogrel) post-ischemic stroke?
a) 21 days
b) 30 days
c) 90 days
d) 365 days
Pre-Test Question 2
A 59 y/o F presents to the ED with unilateral weakness,
confusion, and visual abnormalities. PMH includes DM2,
HTN, and HLD. Current medications include metformin
1000 mg BID, lisinopril 20 mg QD, and atorvastatin 80 mg
QHS. Pt reports an allergy to salicylates (trouble
breathing). She is ultimately diagnosed with a TIA. Which
of the following is the most appropriate secondary
prevention therapy following DAPT?
a) Aspirin 325 mg PO QD
b) Clopidogrel 75 mg PO QD
c) Dipyridamole ER/Aspirin 200/25 mg PO BID
d) Any of the above are options
Pre-Test Question 3
Which of the following are signs/symptoms of
CVA/TIA? Select ALL that apply.
a) One-sided facial droop
b) Ability to keep both arms steady and
level when arms are raised
c) Slurred speech
d) Shooting pains down left arm
Pre-Test Question 4
Cerebrovascular Accidents
Clinical, radiological, or pathological
evidence of ischemia or hemorrhage,
involving a defined cerebral vascular
territory
Comprised of hemorrhagic strokes,
ischemic strokes, and transient ischemic
attacks
Cerebrovascular Accidents (CVA)
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
Leading cause of disability among adults
5th leading cause of death in the US
128,982 deaths in 2011
Annual cost of stroke in the US is ~$33.6
billion
Epidemiology
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
Currently 6.6 million stroke survivors
Of those with no documented history of
stroke, 20% of people > 45 years old report
experiencing at least one symptom of
stroke
Occurs at higher rates in African Americans
compared to whites
Epidemiology
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
Risk Factors
Modifiable
Hypertension
Atrial fibrillation
Diabetes
Dyslipidemia
Poor diet/obesity
Smoking
Non-modifiable
Age > 55 years old
Males > females
African Americans
Genetics
Mechanical heart valve
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
May result from:
o Occlusion of a vessel from an embolus
originating from a distant location
o Major artery stenosis leading to hypoperfusion
o Intracranial vessel thrombosis
Leads to:
o Hypoperfusion
o Ischemia
o Cellular necrosis
Ischemic Stroke
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
Similar presentation and etiology as
ischemic stroke but the blockage is
temporary
“Mini-stroke”
10-15% risk of stroke in first 3 months
Transient Ischemic Attack (TIA)
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
Common subtypes:
o Subarachnoid hemorrhage (SAH)
o Intracranial hemorrhage (ICH)
o Subdural hemorrhage (SDH)
May result from:
o Trauma
o Intracranial aneurysm rupture
o Arteriovenous malformation (AVM) rupture
Hemorrhagic Stroke
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
Leads to:
o Mechanical compression
o Inflammation
o Neurotoxin production
Hemorrhagic Stroke
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
Sudden onset
Unilateral weakness
Inability to speak or understand
Vision abnormalities
Difficulty walking, dizziness, loss of balance or
coordination
Severe headache with no known cause
Clinical Presentation
REFERENCES: Stroke. 2014; 45: 1-93.
ACT F.A.S.T.
Face → Ask the person to smile. Does one side of the
face droop?
Arms → Ask the person to raise both arms. Does one
arm drift downward?
Speech → Ask the person to repeat a simple phrase. Is
their speech slurred or strange?
Time → If you observe any of these signs, call 911
immediately and note the time of the first symptom
onset.
Clinical Presentation
REFERENCES: Stroke. 2014; 45: 1-93.
Stroke: Neurologic deficit lasting > 24
hours
TIA: Neurologic deficit lasting < 24 hours,
but more commonly < 30 minutes
Indistinguishable: Neurologic deficit lasting
< 24 hours but > 1 hour
Clinical Presentation Timeline
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
Diagnosis
All Patients Select Patients
Brain CT or MRI Hepatic function tests
Blood glucose Toxicology screen
Oxygen saturation Blood alcohol level
Basic Metabolic Panel (BMP) Pregnancy test
Complete Blood Count (CBC) Arterial Blood Gas (ABG)
Markers of cardiac ischemia Chest radiography
Prothrombin time/INR Lumbar Puncture
EKG EEG
REFERENCES: Stroke. 2014; 45: 1-93.
Reduce neurologic injury,
mortality, and long-term disability
Prevent secondary complications
Prevent recurrence
Goals of Treatment
REFERENCES: Stroke. 2018;49:e46–e110.
Focus on Ischemic Stroke
Hypertension
o Goal BP <140/90 mmHg
Hyperlipidemia
o High-intensity statin as indicated per ACC/AHA 2013 lipid
guidelines
Diabetes
o Treat per ADA guidelines
Primary Prevention
REFERENCES: Stroke. 2013; 870-947.
Lifestyle changes
o Smoking cessation
o Limit alcohol
o DASH diet
o Exercise
o Screen for sleep apnea
Atrial fibrillation (Afib)
o Non-valvular → Direct-Acting Oral Anticoagulants
(DOACs) preferred
o Valvular → Warfarin
Primary Prevention
REFERENCES: Stroke. 2013; 870-947.
Early rehabilitation
Early revascularization
o Stent placement
o Recanalization via mechanical devices
o Intra-aortic balloon
Ultrasound-enhanced intravenous
thrombolysis
Non-Pharmacologic Treatments
REFERENCES: Frontiers in Neurology. 2011;2:32.
Maintain cerebral perfusion pressure
Maintain normal intracranial pressure
Blood pressure control
Remove/dissolve clot (if possible)
Acute Pharmacologic Treatment
REFERENCES: Stroke. 2014; 45: 1-93.
Recombinant Tissue Plasminogen Activator
Recommend treatment within 3 hours of onset of
symptoms
o Expanded to 4.5 hours
Dosing: 0.9 mg/kg IV (90 mg maximum dose) over 60
minutes
o 10% given as bolus over 1 minute
o 90% given as continuous infusion over 60 minutes
Many contraindications/exclusion criteria
Alteplase (tPA) IV
REFERENCES: Stroke. 2018;49:e46–e110.
Continue measures discussed in primary
prevention section
If cardioembolic source: initiate
anticoagulation therapy
If non-cardioembolic or TIA: initiate
antiplatelet therapy
Secondary Prevention
REFERENCES: Stroke. 2018;49:e46–e110.
Antiplatelet therapy & avoid alcohol
Blood pressure control
Cholesterol control & Cessation of smoking
DASH diet & Diabetes control
Exercise
Secondary Prevention
REFERENCES: Stroke. 2018;49:e46–e110.
Initial therapy
o Aspirin 75-325 mg PO daily (first line)
o Aspirin 25 mg/dipyridamole ER 200mg PO twice daily
o Clopidogrel 75 mg PO daily
Dual Antiplatelet therapy
o Aspirin + Clopidogrel
▪ Recommended for a maximum of 21 days post-
stroke
Antiplatelet Therapy
REFERENCES: Stroke. 2018;49:e46–e110.
Clopidogrel in High-Risk Patients with Acute Non-
disabling Cerebrovascular Events (CHANCE)
o Double-blind, placebo controlled RCT in Chinese population
o Primary outcome: recurrent stroke at 90 days (ischemic or
hemorrhagic)
o Treatment Arms (initiated within 24 hours after minor ischemic
stroke or high-risk TIA onset)
▪ Clopidogrel (300 mg initial dose, then 75 mg/day for 90
days) + Aspirin (75 mg/day for first 21 days)
▪ Placebo + Aspirin (75 mg/day for 90 days)
CHANCE Trial Overview
REFERENCES: NEJM. 2013;369:11.
Primary Outcome
o Occurred in 8.2% of patients in ASA + clopidogrel
group compared to 11.7% in ASA +Placebo group
(HR 0.68, 95% CI 0.57-0.81, p<0.001, NNT = 29)
2018 New AHA/ASA Guideline Recommendation
o Class IIa, level B Moderate recommendation
o Recommend DAPT for 21 days post-stroke
CHANCE Trial Outcome
REFERENCES: NEJM. 2013;369:11
Stroke. 2018;49:e46–e110.
Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT)
o Double-blind, placebo controlled RCT in international population
o Primary outcome: time-to-event for composite of major ischemic events (ischemic stroke, MI, or death from ischemic vascular event) at 90 days
o Treatment Arms (initiated within 12 hours after minor ischemic stroke or high-risk TIA onset)
▪ Clopidogrel (600 mg initial dose, then 75 mg/day)+ Aspirin (50 to 325 mg/day) for 90 days
▪ Aspirin (50 to 325 mg/day) for 90 days
POINT Trial Overview
REFERENCES: NEJM. doi: 10.1056/NEJMoa1800410
Primary Outcome
o Occurred in 5.0% of patients in ASA + clopidogrel group compared to 6.5% in ASA +Placebo group (HR 0.75, 95% CI 0.59-0.95, p=0.02, NNT = 67)
Safety Outcome (major hemorrhage)
o Occurred in 0.9% of patients in ASA + clopidogrel group compared to 0.4% in ASA +Placebo group (HR 2.32, 95% CI 1.10-4.87, p=0.02, NNH = 200)
Trial was stopped at 84% enrolled due to increase in hemorrhage in DAPT group
POINT Trial Outcome
REFERENCES: NEJM. doi: 10.1056/NEJMoa1800410
Comparison of Anti-Platelet TherapiesAnti-Platelet
Therapy MOA Contraindications Comments
Aspirin
Irreversibly inhibits COX-1
& COX-2 which decreases
thromboxane &
prostaglandins
NSAID or salicylate allergy
Syndrome of asthma,
rhinitis, nasal polyps
(known hypersensitivity)
Cheapest
Risk of GI hemorrhage
Aspirin +
Dipyridamole
Same as above + inhibits
uptake of adenosine into
platelets which increases
cAMP & indirectly inhibits
platelet aggregation
NSAID or salicylate allergy
Syndrome of asthma,
rhinitis, nasal polyps
(known hypersensitivity)
Keep in original container
Amount of aspirin is not
adequate for cardiac
indications
Clopidogrel
Inhibits P2Y12 mediated
platelet activation &
aggregation
Active bleeding
Discontinue 5 days before
surgery
Do not use in pt with
upcoming CABG
Metabolized by CYP2C19
REFERENCES: Stroke. 2018;49:e46–e110.
Aspirin 81 mg vs. 325 mg
Ticagrelor
o SOCRATES trial
o Ticagrelor was not found to be superior to
aspirin (HR = 0.89, 95% CI [0.78-1.01], P=0.07)
in 90 day outcomes of stroke, MI, or death
o Not recommended over aspirin in Acute
Ischemic Stroke/TIA
Prasugrel
o No data/No recommendation
Other antiplatelet therapies
REFERENCES: Stroke. 2018;49:e46–e110, The New England journal of medicine. 2016;375:35-43.
Antiplatelet therapy & avoid alcohol
Blood pressure control
Cholesterol control & Cessation of smoking
DASH diet & Diabetes control
Exercise
Secondary Prevention
REFERENCES: Stroke. 2018;49:e46–e110.
Restart home BP medications
Treat aggressively if no tPA was given and
BP > 220/110 mmHg for acute treatment
Initiate anti-hypertensive medication if SBP
> 140/90 mmHg (weak recommendation)
o ACE-I/ARB (first-line), diuretics, CCBs
Blood Pressure Management
REFERENCES: Stroke. 2018;49:e46–e110.
Antiplatelet therapy & avoid alcohol
Blood pressure control
Cholesterol control & Cessation of smoking
DASH diet & Diabetes control
Exercise
Secondary Prevention
REFERENCES: Stroke. 2018;49:e46–e110.
SPARCL Study
o Recommend high intensity statin regardless of
baseline LDL-C levels in all patients with acute
ischemic stroke
▪ Atorvastatin 80 mg PO daily
o Goal LDL <100 or <70 mg/dL
o Benefits in addition to LDL lowering capabilities
▪ Decrease inflammation
▪ Stabilize plaques
▪ Prevent blood clots
Cholesterol Control
REFERENCES: NEJM. 2006;355:549-559.
Questions??
What is/are modifiable risk factors for
cerebrovascular accidents (CVA)/ Transient Ischemic
Attacks (TIA)? Select ALL that apply.
a) Diabetes
b) Hypertension
c) Cigarette smoking
d) Obesity
Post-Test Question 1
Which of the following is/are modifiable risk factors
for CVA/TIA ? Select ALL that apply.
a) Diabetes
b) Hypertension
c) Cigarette smoking
d) Obesity
Post-Test Question 1
Explanation: The most common risk factors that can be
modified are hypertension, cigarette smoking, diabetes,
dyslipidemia, and atrial fibrillation. The most common
contributor to CVA/TIA in the United States is hypertension
which affects approximately 1 in 3 adults. Obesity also
increases the risk of developing a TIA in that it predisposes
patients to many relevant comorbidities.
Post Test Question #1 Feedback
REFERENCES: Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e New York, NY: McGraw-Hill; 2014.
What is the recommended duration of treatment
for dual antiplatelet therapy (aspirin and
clopidogrel) post-ischemic stroke?
a) 21 days
b) 30 days
c) 90 days
d) 365 days
Post-Test Question 2
What is the recommended duration of treatment
for dual antiplatelet therapy (aspirin and
clopidogrel) post-ischemic stroke?
a) 21 days
b) 30 days
c) 90 days
d) 365 days
Post-Test Question 2
RESOURCE: NEJM. 2013;369:11.
Explanation: Combination antiplatelet therapy is
only appropriate for a maximum of 21 days after a
CVA/TIA event. After 21 days of DAPT, it is
recommended to use antiplatelet monotherapy.
Post Test Question #2 Feedback
REFERENCES: Stroke. 2018;49:e46–e110.
JB a 59 y/o F presents to the ED with unilateral
weakness, confusion, and visual abnormalities. PMH of
DM2, HTN, and HLD. JB is currently taking metformin
1000 mg BID, Lisinopril 20 mg QD, and simvastatin 20 mg
QHS. JP reports an allergy to salicylates. JB is diagnosed
with a TIA. Which is the most appropriate secondary
prevention therapy after DAPT?
a) Aspirin 325 mg PO QD
b) Clopidogrel 75 mg PO QD
c) Dipyridamole ER/Aspirin 200/25 mg PO BID
d) Any of the above are options
Post-Test Question 3
JB a 59 y/o F presents to the ED with unilateral
weakness, confusion, and visual abnormalities. PMH of
DM2, HTN, and HLD. JB is currently taking metformin
1000 mg BID, Lisinopril 20 mg QD, and simvastatin 20 mg
QHS. JP reports an allergy to salicylates. JB is diagnosed
with a TIA. Which is the most appropriate secondary
prevention therapy after DAPT?
a) Aspirin 325 mg PO QD
b) Clopidogrel 75 mg PO QD
c) Dipyridamole ER/Aspirin 200/25 mg PO BID
d) Any of the above are options
Post-Test Question 3
Explanation: Although aspirin is the first line
therapy for secondary prevention of TIA.
Clopidogrel 75 mg monotherapy is a reasonable
option for secondary prevention of stroke in place
of aspirin or combination aspirin/dipyridamole
(Class IIa, Level B). Therefore, in a patient who is
aspirin/salicylate allergic, Clopidogrel is the
preferred option.
Post Test Question #3
REFERENCES: Stroke. 2018;49:e46–e110.
Which of the following are signs/symptoms of
CVA/TIA? Select ALL that apply.
a) One-sided facial droop
b) Ability to keep both arms steady and
level when arms are raised
c) Slurred speech
d) Shooting pains down left arm
Post-Test Question 4
Which of the following are signs/symptoms of
CVA/TIA? Select ALL that apply.
a) One-sided facial droop
b) Ability to keep both arms steady and
level when arms are raised
c) Slurred speech
d) Shooting pains down left arm
Post-Test Question 4
The acronym “FAST” is used to identify common stroke symptoms?
F: Face → Ask the person to smile. Does one side of the face droop?
A: Arms → Ask the person to raise both arms. Does one arm drift downward?
S: Speech → Ask the person to repeat a simple phrase. Is their speech slurred or strange?
T: Time → If you observe any of these signs, call 911 immediately and note the time of the first symptom onset.
Post Test Question #4 Feedback
REFERENCES:. Stroke. 2014; 45: 1-93.
Remember to ACT F.A.S.T.
Time is Brain
Early detection & intervention is crucial
Primary prevention aims to reduce modifiable risk
factors of stroke such as hypertension, Afib, &
cigarette smoking
Secondary prevention of ischemic stroke is as easy
as ABCDE
Initiate antiplatelet therapy in all patients, unless
contraindicated
TAKE HOME POINTS
References
1. Fagan SC, Hess DC. Chapter 10. Stroke. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=689§ionid=45310472. Accessed March 13, 2018.
2. Smith WS, Johnston S, Hemphill J, III. Cerebrovascular Diseases. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, LoscalzoJ. eds. Harrison's Principles of Internal Medicine, 19e New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1130§ionid=79755261. Accessed July 17, 2018.
3. Kernan WN, et al; on behalf of the American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Counsel on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014; 45: 1-93.
4. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke regarding: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46–e110.
5. Jauch EC, et al; on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Nursing, Counsel on Peripheral Vascular Disease, and Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013; 870-947.
6. Frendl A, Csiba L. Pharmacological and Non-Pharmacological Recanalization Strategies in Acute Ischemic Stroke. Frontiers in Neurology. 2011;2:32. doi:10.3389/fneur.2011.00032.
7. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. NEJM. 2013;369:11.
8. Johnston SC, Easton D, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA [published online ahead of print May 16, 2018]. NEJM. doi: 10.1056/NEJMoa1800410
9. Amarenco P, Bogousslavsky J, Callahan E, Alfred, et al. High-Dose Atorvastatin after Stroke or Transient Ischemic Attack. NEJM. 2006;355:549-559.
10. Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. The New England journal of medicine. 2016;375:35-43.
Resources & References
Speaker Contact Information
Dr. Heather Powell, PharmD, BCPS,
hpowell01@roosevelt.edu
Shayna Cruz, BS, PharmD Candidate,
scruz1@mail.roosevelt.edu
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