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

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Ischemic Stroke

Presentation Outline

2

Background

Pathophysiology

Risk factors of

Epidemiology

Treatment options

Evidence-based treatments

Conclusion

Background

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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

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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

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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,

141(2 Suppl)

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.

Kochanek KD, Xu JQ, Murphy SL, Miniño AM, Kung HC. Deaths: final data for 2009. Nat Vital Stat Rep.[PDF-

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Thomson, R. M., & Anderson, D. C. (2013). Aspirin and clopidogrel for prevention of ischemic stroke. Current

Neurology And Neuroscience Reports, 13(2), 327.

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.