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Secondary Stroke Prevention

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Secondary Stroke Prevention Kris Howard, PharmD, BCPS Clinical Pharmacy Specialist in Cardiology Parkview Regional Medical Center Wednesday, April 15, 2015 – PowerPoint PPT presentation

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Title: Secondary Stroke Prevention


1
Secondary Stroke Prevention
  • Kris Howard, PharmD, BCPS
  • Clinical Pharmacy Specialist in Cardiology
  • Parkview Regional Medical Center
  • Wednesday, April 15, 2015

The speaker has no actual or potential conflicts
of interest in relation to this presentation
2
Objectives
  • Identify the ischemic stroke / transient ischemic
    attack pertinent changes in guideline
    recommendations.
  • Summarize the evidence supporting each
    pharmacological intervention for secondary stroke
    prevention.
  • Detail guidelines focused on prevention in women.
  • Discuss patient complexities key points to
    consider prior to therapeutic intervention.
  • Highlight the pharmacological Joint Commission /
    National Patient Quality Measures with regard to
    stroke /TIA.

3
Stroke in the US
  • Stroke is the fourth leading cause of death
  • 130,000 American deaths annually
  • 800,000 strokes annually
  • 87 are ischemic strokes
  • 1 in 4 in patients with previous stroke
  • Cost of 34 billion year each

4
Stroke in the US
  • Ethnic variation
  • Blacks twice as like to have first stroke
  • More likely to die from stroke
  • In 2009, 34 of stroke hospitalizations for
    people younger than 65 years.
  • Hypertension, hypercholesterolemia, and smoking
    are major risk factors
  • half of American have at least 1

5
Ischemic Stroke
  • Embolization
  • Atrial fibrilation
  • Atherosclerotic disease
  • Local thrombosis

6
Ischemic Stroke
7
Transient Ischemic Attack (TIA)
  • Occur in 240,000 people annually
  • Stroke manifestations lasting lt24 hours
  • Spasm at site of plaque
  • Small emboli
  • No lasting impairment
  • 3-4 likelihood of developing ischemic stroke

8
Manifestations
  • Dependant on area of brain affected
  • Sensory and motor deficits
  • Cognitive ability, memory, personality
  • Frontal or limbic lesions
  • Seizures

9
Guidelines
  • American Heart Association / American Stroke
    Association (AHA/ASA)
  • Guidelines for the Prevention of Stroke in
    Patients with Stroke and Transient Ischemic
    Attack
  • Updated every 2-3 years
  • 2014

10
Hypertension
  • 70 million US adults (29)
  • Only 1/2 are controlled
  • Women gt Men after age 65
  • 80 of all new strokes occur in patients with
    hypertension
  • Degenerative changes in smooth muscle and
    endothelium enhance atherosclerotic changes

11
Lifestyle Modifications
  • Weight Loss
  • Diet rich in fruits, vegetables, low-fat dairy
  • Mediterranean-type diet
  • Reduce sodium intake
  • Regular aerobic activity
  • Limiting alcohol consumption

12
Blood Pressure Management
  • Initiate therapy in untreated patients with
    ischemic stroke or TIA
  • SBP gt/ 140 mmHg, DBP gt/ 90 mmHg
  • No specific drug recommendations
  • Individualized to patient
  • Diuretics or Diuretic ACE Inhibitor

13
Target Blood Pressure
  • 4733 patient with type 2 diabetes
  • Mean follow-up 4.7 years
  • Randomized to goal SBP lt140 mmHg vs. lt120 mmHg
  • Non-significant improvement in annual composite
    endpoint
  • Recommended goal lt140 mmHg

14
Blood Pressure Management
  • Resume therapy in previously treated patients for
    prevention of recurrence
  • May restart with 24 hours of previous stroke if
  • Treatment with t-PA
  • SBP gt220 mmHg
  • DBP gt120 mmHg

15
Blood Pressure Management
  • Optimal blood pressure goal uncertain
  • SBP gt140 mmHG, DBP lt90 mmHg
  • Lacunar stroke SBP lt130 mmHg

16
Hyperlidemia
  • 73.5 million US adults (31.7) have high LDL
  • Only lt1/2 receiving treatment
  • Increase in atherosclerotic plaques

17
Atherosclerotic Disease
  • Plaque formation
  • Low Density lipoprotein (LDL) accumulation
  • Oxidation of the LDL
  • Recruitment of monocytes and macrophages
  • LDL uptake into macrophages
  • Creation of foam cells
  • Fibrous cap formation

18
Atherosclerotic Disease
19
Statin Therapy
  • Decrease LDL deposition and plaque growth
  • Statin for intensive lipid-lowering in patients
    with stroke / TIA and
  • LDL-C gt/ 100 without evidence of ASCVD
  • LDL-C lt 100 presumed to be due to atherosclerotic
    disease

20
Statin for Stroke Prevention
  • 2009 Meta-Analysis
  • Primary and secondary prevention trials
  • gt165,000 patients included
  • 18 reduction in all strokes (plt0.0001)
  • SPARCL
  • Secondary Prevention
  • 5-year Absolute Risk Reduction 2.2

21
Antithrombotic Therapy
  • Cardioembolic Ischemic Stroke
  • Noncardioembolic Ischemic Stroke

22
Cardioembolic Ischemic Stroke
  • Atrial fibrillation
  • gt2.7 million Americans
  • gt 70,000 ischemic stroke annually in US
  • Annual risk of stroke
  • CHADS2
  • CHA2DS2VASc

23
Cardioembolic Ischemic Stroke
  • Warfarin
  • Both primary and secondary prevention of stroke
    in a-fib patients vs. placebo
  • Optimal goal INR 2-3
  • INR time within therapeutic range is 58

24
Cardioembolic Ischemic Stroke
  • Antiplatelet agents
  • For warfarin contraindication
  • Aspirin recommended
  • Addition of clopidogrel to aspirin might be
    reasonable
  • No indication for combination of warfarin plus
    antiplatelet
  • Exception CAD or stent placement

25
Cardioembolic Ischemic Stroke
  • Dabigatran
  • Oral direct thrombin inhibitor
  • Open-label trial with 18,000 subjects
  • Dabigatran 150 mg BID non-inferiority to warfarin

26
Cardioembolic Ischemic Stroke
  • Rivaroxaban
  • Oral Factor Xa Inhibitor
  • Double-blind trial with 14,265 subjects
  • Rivaroxaban 20 mg daily non-inferior to warfarin
  • Major gastrointestinal bleeding

27
Cardioembolic Ischemic Stroke
  • Apixaban
  • Oral Factor Xa Inhibitor
  • Double-blind trial with 18,201 subjects
  • Apixaban 5mg daily superior to warfarin
  • Bleeding rates decreased

28
Cardioembolic Ischemic Stroke
  • Warfarin, apixaban, and dabigatran most highly
    recommended
  • Rivaroxban is reasonable for use

29
MI and Thrombus
  • Warfarin recommended for 3 months
  • INR goal 2 3
  • If warfarin contraindicated
  • With additional complications
  • LMWH, dabigatran, rivaroxaban, apixaban

30
  • Which of the following is true regarding the
    current recommendations for secondary prevention
    of stroke in patients with Atrial Fibrillation?
  • Warfarin is ONLY first-line recommendation
  • Dabigatran, Rivaroxaban, and Apixaban carry same
    level of recommendation
  • Warfarin, Apixaban, and Dabigatran all most
    highly recommended
  • Antiplatelet agents are recommneded first-line.

31
Noncardioembolic Stroke
  • Intracranial Atherosclerosis

32
Intracranial Atherosclerosis
  • Major artery occlusive disease
  • 2-year stroke recurrence rate 17-20
  • Race-ethnic variation
  • Asian, blacks
  • Females
  • High blood volume states
  • Diabetes

33
Noncardioembolic Stroke
  • Antiplatelet agents recommended over oral
    anticoagulants
  • Aspirin or aspirin dipyridamole
  • Clopidogrel is a reasonable alternative
  • Aspirin allergic patients
  • Individualized based on patient risk factors

34
Antiplatelet Therapy
  • Aspirin
  • Lowers risk of secondary stroke by 15
  • Gastrointestinal bleeding
  • 0.4 with doses lt/ 325 mg /day
  • Increased risk of hemorrhagic stroke
  • Net benefit

35
Antiplatelet Therapy
  • Ticlopidine
  • Platelet ADP receptor antagonist
  • Limited trials

36
Antiplatelet Therapy
  • Clopidogrel
  • Platelet ADP receptor antagonist
  • Safety comparable with aspirin
  • CYP2C19 interactions

37
Antiplatelet Therapy
  • Dipyridamole and Aspirin
  • Phosphodiesterase inhibitor
  • prostacyclin-mediated
  • At least as effective as aspirin alone
  • Less well tolerated

38
Antiplatelet Therapy
  • Cilastazol
  • Phosphodiesterase inhibitor
  • Limit progression of intracranial stenosis

39
Intracranial Athersclerosis
  • 3 recent antiplatelet trials
  • Magnetic resonance angiography
  • Cilastazol aspirin vs. aspirin
  • Cilastazol vs. clopidogrel
  • Transcranial Doppler
  • Clopidogrel aspirin vs. aspirin
  • No clinical outcomes in any study

40
Intracranial Atherosclerosis
  • For Stroke / TIA caused by 50-99 stenosis of
    major intracranial artery
  • Aspirin 325 mg/day
  • Insufficient data to support
  • Clopidogrel alone
  • Aspirin dipyridamole
  • Cilastazole alone

41
Intracranial Athersclerosis
  • For recent Stroke / TIA due to 70-99 stenosis of
    major intracranial artery
  • Clopidogrel 75 mg daily for 90 days
  • For Stroke / TIA due to 50-99 stenosis of major
    intracranial artery
  • Keep SBP below 140 mmHg
  • High intensity statin

42
Noncardioembolic Stroke
  • Routine long-term use of aspirin clopidogrel is
    not recommended
  • May be used for 90 days when initiated within 24
    hours of minor ischemic stroke or TIA
  • For stroke while taking aspirin
  • No evidence for increasing aspirin dose
  • Consider alternate agent

43
  • Which of the following is NOT recommended for
    secondary stroke prevention in intracranial
    atherosclerosis?
  • Aspirin 325 mg daily
  • Add Clopidogrel 75 mg daily to Aspirin for 90
    days for recent stroke / TIA
  • Maintain SBP lt 140 mmHg
  • High Dose Statins
  • All of the above are recommended

44
Secondary Prevention in Women
45
Secondary Prevention in Women
  • Few recommendations specific to women
  • For hyperlipidemia, hypertension, diabetes, and
    other disease states
  • Follow specific recommendations in those
    guidelines
  • Pregnancy and Breastfeeding

46
Secondary Prevention in Women
  • Pregnancy
  • 4-26 per 100,000 deliveries
  • Increased risk for recurrence post-partum
  • Similar to primary risk during 9 months of
    pregnacy
  • Overall recurrence rate 1 in 143 (0.7)

47
Pregnancy Antithombotic Therapy
  • High Risk Conditions
  • Warfarin crosses placenta (first trimester)
  • In mechanical heart valves
  • UFH and LMWH have increased valve thrombosis and
    maternal thromboembolism than warfarin
  • Consider adding aspirin 75-100 mg daily
  • Pharmacokinetic changes in pregnant woman may
    affect LMWH dosing over time

48
Pregnancy Antithombotic Therapy
  • High Risk Conditions
  • LMWH every 12 hours with peak anti-Xa level 4
    hours after injection
  • Adjusted-dose UFH subcutaneously every 12 hours
    to keep midinterval aPTT gt2X control
  • Or goal anti-Xa heparin level 0.35 to 0.70 U/mL
  • UFH or LMWH until 13th week, followed by warfarin
    until close to deliver, then resume UFH or LMWH

49
Pregnancy Antithombotic Therapy
  • Lower Risk Conditions
  • Low dose aspirin is safe after first trimester
  • No increased bleeding
  • No increased risk of malformation
  • No adverse effects on early childhood development
  • Aspirin crosses placenta an may affect organ
    development in first trimester
  • Other antiplatelet agents not studied

50
Pregnancy Antithombotic Therapy
  • Lower Risk Conditions
  • Heparin does not cross placenta
  • Efficacy not defined for antiplatelet indications
  • Useful for cardioembolic stroke
  • No consensus on best alternative in first
    trimester

51
Pregnancy Antithombotic Therapy
  • Lower Risk Conditions
  • During first trimester
  • UFH or LMWH or no treatment may be considered
    depending on clinical situation
  • After first trimester
  • Low dose aspirin (50-150 mg / day) is reasonable

52
Secondary Prevention in Women
  • Breast Feeding
  • Warfarin does not pass into breast milk
  • Other vitamin K antagonist not known
  • Heparin undetectable in breast milk
  • LMWH detectable in low concentration
  • Poor oral bioavailability
  • High dose aspirin can lead to Reyes Syndrome

53
Breast Feeding
  • High Risk Conditions
  • Warfarin, UFH, or LMWH reasonable choices
  • Low Risk Conditions
  • Consider low-dose aspirin

54
  • Which of the following is true regarding LMWH in
    high-risk breastfeeding patients?
  • LMWH is not detectable in breast milk and may be
    administered
  • LMWH is detectable in breast milk and should not
    be administered
  • LMWH is detectable in breast milk but may be
    administered due to poor oral bioavailability
  • None of the above

55
Patient Complexities
56
Diabetes Mellitus
  • 11.3 US population has diabetes
  • 26.9 gt/ 65 year of age
  • Increased risk for first ischemic stroke
  • Up to 8 of first strokes
  • 60 increased risk of recurrent stroke
  • Insulin resistance associated with doubling risk
    of ischemic stroke

57
Diabetes Mellitus
  • All TIA / stroke patients should be screened for
    diabetes
  • Fasting glucose, HbA1C, oral glucose tolerance
    test
  • No specific information for management in TIA /
    stroke patients
  • Standard ADA guidelines

58
Body Mass and Health
  • Obesity and over-nutrition affect cardiovascular
    risk factors
  • No specific recommendations for modification
  • Dietary referral for under-nutrition
  • Physical activity
  • Refer patients to compehensive,
    behaviorally-oriented program

59
Occult Atrial Fibrillation
  • 10 of patient with acute ischemic stroke or TIA
    have newly-detected A-fib
  • Additional 11 may be found to have a-fib if
    tested with a 30 day monitor at discharge
  • Interrogation of pacemaker indentified 28
    incidence A-fib during one year

60
Additional Complexities
  • Sleep Apnea
  • Sleep study may be considered if indicated
  • CPAP has demostrated improved outcomes
  • Homocysteinemia
  • Routine screening not indicated
  • Lowering with folate, B6, and B12 no shown to
    decrease stroke

61
Regulatory
62
Quality Measures
  • Joint Commission / National Patient Quality
    Measures
  • In November 2003, the Joint Commission began work
    with AHA/ASA to create Certification for Primary
    Stroke Centers
  • Continued revisions into current eight
    standardized measures for stroke.

63
Quality Measures
STK-1 Venous Thromboembolism (VTE) Prophylaxis
STK-2 Discharged on Antithrombotic Therapy
STK-3 Anticoagulation Therapy for Atrial Fibrillation/Flutter
STK-4 Thrombolytic Therapy
STK-5 Antithrombotic Therapy by the End of Hospital Day 2
STK-6 Discharged on Statin Medication
STK-8 Stroke Education
STK-10 Assessed for Rehabilitation
64
Quality Measures STK-2
  • Discharged on Antithrombotic Therapy
  • Reduce mortality, morbidity and recurrence
  • Regular use unless contraindicated
  • Cardioembolic source

65
Quality Measures STK-3
  • Anticoagulation Therapy for Atrial
    Fibrillation/Flutter
  • Discharge home on anticoagulation
  • No specification of agent

66
Quality Measures STK-6
  • Discharged on a statin
  • Still based on the ATP III guidelines and LDL
    goals

67
Wrap-up
  • 3-4 of stroke patients will have recurrent
    stroke
  • 2014 Guidelines for Secondary Prevention of
    Stroke
  • Updated every few years
  • Consistent with other guidelines
  • Eg. Hypertension, hyperlipidemia, diabetes, etc.

68
Wrap-up
  • Stroke can be caused by atherosclerosis within
    the cerebrovascular vessels or be embolization
    from other vessels or the heart
  • Antiplatelet agents, statins, antihypertensives
    useful to reduce plaque formation and rupture

69
Wrap-up
  • Anticoagulants indicated to reduce embolization,
    including atrial fibrillation/flutter and
    mechanical heart valve
  • Selection of agents based on patient factors,
    including pregnancy and lactation
  • Screening for risk factors may guide treatment to
    reduce recurrence

70
References
  • Mayo Clin Proc. 200984(1)43-51
  • http//www.cdc.gov/stroke/facts.htm accessed
    2015_02_27
  • http//www.webmd.com/stroke/ischemic-stroke
    accessed 2015_02_27
  • Kernan WN, et.al. Stroke. 20144500-00
  • http//www.cdc.gov/bloodpressure/facts.htm
    accessed 2015_02_27
  • N Engl J Med 20103621575-85
  • Am J Cardiol 200799suppl44i55i
  • Jauch EC, et al. Stroke. 201344870947
  • http//www.cdc.gov/cholesterol/facts.htm accessed
    2015_02_27
  • Libby P.,Pathogenesis of Athersclerosis. In
    Harrisons Principles of Internal Medicaine. 15th
    Edition.2001
  • http//php.med.unsw.edu.au/medwiki/images/c/c4/Gen
    eral_atherosclerosis.png accessed 2015_03_11

71
References
  • Lancet Neurol 2009 8 45363
  • N Engl J Med 2006355549-59
  • Stroke. 2008392396-2399
  • Chest. 2008133(suppl)546S592S
  • http//www.qualitymeasures.ahrq.gov/content.aspx?i
    d32739 accessed 2015_03_14
  • N Engl J Med. 200936111391151
  • N Engl J Med 2011365883-91
  • N Engl J Med 2011365981-92
  • Joint Commission Stroke Performance Measurement
    Implementation Guide, 2nd Edition
  • http//www.jointcommission.org/assets/1/6/Stroke.p
    df accessed 2015_03_24

72
Secondary Stroke Prevention
  • Kris Howard, PharmD, BCPS
  • kris.howard_at_parkview.com
  • Clinical Pharmacy Specialist in Cardiology
  • Parkview Regional Medical Center
  • Wednesday, April 15, 2015
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