ischemic stroke-dbediako1
TRANSCRIPT
Daniel Bediako, Pharm.D Candidate 2015
APPE Preceptor:
Kyle Simmons, Pharm.D, BCPS
Clinical Pharmacy Specialist, Internal Medicine
Ochsner Health System – Elmwood Campus
February 2015
1
Ischemic Stroke
Presentation Outline
2
Background
Pathophysiology
Risk factors of
Epidemiology
Treatment options
Evidence-based treatments
Conclusion
Background
3
Definition:
“A stroke, or cerebrovascular accident, occurs when blood flow
to an area of the brain is interrupted by ischemia due a clot
(thrombus or emboli) or a ruptured blood vessel (hemorrhage)”.
Shapiro et al. (2014)
Signs and symptoms:
muscle weakness, numbness in face, arm, or leg
confusion, loss of coordination and balance
dysphonia and dysphagia
Pathophysiology
4
Pathophysiology
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Thrombus Formation
progressive accumulation of lipids and inflammatory cells in the
intima of the affected arteries,
hypertrophy of arterial smooth muscle cells results in plaque
formation.
sheer stress may result in plaque rupture, collagen exposure,
platelet aggregation, and clot formation.
Emboli Formation
Clot formed in the periphery, breaks off and travels to the brains
through the aorta to the cerebral circulation.
Risk Factors
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Nonmodifiable
Age > 55 years
Gender: males > females
Race: African American,
Asian, Hispanic
Family history
Low birth weight
Previous stroke/TIA
Modifiable
Hypertension
Atrial Fibrillation
Diabetes mellitus
Dyslipidemia
Cigarette Smoking
Lifestyle
obesity, excessive alcohol
intake
Epidemiology
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Stroke kills almost 130,000 Americans each year
On average, one American dies from stroke every 4 minutes
Every year, more than 795,000 people in the United States have
a stroke.
About 610,000 of these are first or new strokes.
About 185,000 strokes—nearly one of four—are in people
who have had a previous stroke.
About 87% of all strokes are ischemic strokes
Alteplase
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MOA: directly activates plasminogen to form plasmin which
leads to clot lysis
Dose: 0.9 mg/kg IV over 60 mins; 10% of the dose is given as
bolus over 1 minute
Side effects:
major bleeding, hypotension, angioedema, nausea and vomiting
Drug interactions: P2Y12 inhibitors, NSAIDs, SSRIs
Contraindications:
active bleed, low platelet count, INR ˃1.7, elevated BP
Severe head injury within the past 3 months, oral anticoagulants use,
Aspirin
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MOA: irreversibly acetylates cox-1, blocking thromboxane-a2 synthesis and
inhibiting platelet activation and aggregation
Dose:
Initial: 160-325 mg within 48 hours of stroke; then 75-100 mg QD
Side effects:
GI ulceration, increased BP, heartburn, hypersensitivity, tinnitus
Drug Interactions: P2Y12 inhibitors, NSAIDs, SSRIs,
Contraindications:
NSAID or salicylate allergy; children less than 16yrs; rhinitis, asthma and
nasal polyps syndrome
Discontinue 7 to 10 days before surgery
Clopidogrel
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MOA: irreversible inhibitor of P2Y12 platelet receptors
Dose: loading dose is 300-600 mg; then 75 mg QD
Side effects:
GI bleeding, diarrhea, neutropenia, thrombocytopenia, rash
Drug Interactions: CYP2C19 inhibitors and polymorphisms
Do not give with cimetidine, fluoxetine, esomeprazole,
fluconazole, etc.
Contraindications:
active pathological bleeding: PUD, ICH
Discontinue 5-10 days before surgery
Aspirin/Dipyridamole ER
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MOA:
Dipyridamole inhibits the uptake of adenosine into platelets, endothelial cells,
and erythrocytes.
Aspirin inhibits platelet aggregation by irreversible inhibition of platelet
cyclooxygenase and thus inhibits the generation of thromboxane A2.
Dose: 25/200 mg BID
Side effects:
headache, abdominal pain, nausea, diarrhea, vomiting, dyspepsia
Drug Interactions:
P2Y12 inhibitors, NSAIDs, SSRIs,
Contraindications:
NSAID or salicylate allergy; children less than 16yrs; rhinitis, asthma and
nasal polyps syndrome
Cilostazol
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MOA: reversibly Inhibits platelet phosphodiesterase-3
Dose: 100 mg BID
Side Effects:
headache, palpitations, diarrhea
Drug Interactions:
CYP3A4, CYP2C19
Contraindications: heart failure
Discontinue 2-3 days before surgery
Clinical Question
13
Is the combo Aspirin and Clopidogrel better than individual
agents?
Efficacy and Safety of Adding Clopidogrel to Aspirin on Stroke
Prevention among High Vascular Risk Patients: A Meta-Analysis
of Randomized Controlled Trials
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Purpose:
to assess the efficacy and safety of adding clopidogrel to aspirin on stroke prevention in high vascular risk patients, and to provide evidence for a suitable duration of dual antiplatelet
Methods:
PubMed, OVID and Cochrane Central Register of Controlled Trials (up to June, 2013)
Participants: 97,692
Results:
Dual antiplatelet therapy reduced all stroke by 21%
The risk of major bleeding was not significantly increased by dual antiplatelet therapy in short-term subgroup, while significantly increased in long-term subgroup
Long-term dual antiplatelet therapy substantially increased the risk of intracranial bleeding
Clopidogrel with Aspirin in Acute Minor Stroke or Transient
Ischemic Attack
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Purpose:
The CHANCE trial was to test the hypothesis that 3 months
treatment with a combination of clopidogrel and aspirin would
reduce the risk of recurrent stroke, as compared with aspirin
alone.
Methods:
a randomized, double-blind, placebo-controlled trial conducted at
114 centers in China
Participants: 5,170
Results:
Stroke occurred in 8.2% of patients in the clopidogrel–aspirin
group, as compared with 11.7% of those in the aspirin group
Conclusion
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Short-term combination of clopidogrel and aspirin is effective and
safe for stroke prevention in high vascular risk patients.
Long-term combination therapy substantially increases the risk of
major bleeding and intracranial bleeding.
The combination of clopidogrel and aspirin is superior to aspirin
alone for reducing the risk of stroke and does not increase the
risk of hemorrhage
Works Cited
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Chen, S., Shen, Q., Tang, Y., He, L., Li, Y., Li, H., & ... Peng, Y. (2014). Efficacy and safety of adding clopidogrel
to aspirin on stroke prevention among high vascular risk patients: a meta-analysis of randomized controlled trials.
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Lansberg, M. G., O'Donnell, M. J., Khatri, P., Lang, E. S., Nguyen-Huynh, M. N., Schwartz, N. E., & ... Akl, E. A.
(2012). Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest,
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Lexicomp online (2015). http://online.lexi.com.ezproxy.xula.edu. (01/28/2015)
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al (2014). Heart disease and stroke
statistics—2014 update: a report from the American Heart Association. Circulation. 2014 ;128.
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Wang, Y., Wang, Y., Zhao, X., Liu, L., Wang, D., Wang, C., & ... Johnston, S. C. (2013). Clopidogrel with aspirin in
acute minor stroke or transient ischemic attack. The New England Journal Of Medicine, 369(1), 11-19.