stroke symposium talk on secondary prevention

Secondary Stroke Prevention- 2016

Jonathan Artz, MD

September 8, 2016

Neurology Department Kaiser Permanente San Rafael

Objectives

1. Review major factors related to Secondary Stroke Prevention as emphasized in the recently updated guidelines for both Kaiser Permanente Northern California Stroke Care and the American Heart/Stroke Association.

2. Review key medical management features in Secondary Stroke Prevention through three clinical vignettes.

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TIA vs Stroke TIA: New Definition Is Proposed (2002) Definition:Brief episode of neurologic dysfunction caused by focal brain or retinal ischemia

•Clinical symptoms typically lasting less than 1 hour

•No evidence of cerebral infarction (using advanced neuroimaging techniques)

•Urgent brain imaging is recommended

•Albers GW et al. N Engl J Med. 2002;347(21):1713

Rationale : Traditional definition is out of date and no longer consistent with current

•concepts of brain ischemia

•• Most TIAs are short lived, and advanced imaging techniques may show

•cerebral ischemic injury

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TOAST Classification1. Large Artery Atherosclerosis

2. Small Vessel Arterial Occlusion/ Ischemia

3. Cardioembolism

4. Other Determined Cause (Venous,Air Embolism).

5. Cryptogenic (Undetermined)

Stroke Vol 24, No 1 January 19934

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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.

Endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons

(Stroke. 2014;45:00-00.)

http://stroke.ahajournals.org/content/early/2014/04/30/STR.0000000000000024

Definitions of Classes and Levels of Evidence:

AHA/ASA 2014 Stroke Prevention Guidelines

Class I Evidence or general agreement that procedure or treatment is useful and effective.

Class II Conflicting evidence or divergence of opinion of usefulness/efficacy

Class IIa Weight of evidence or opinion is in favor

Class IIb Usefulness/efficacy is less well established by evidence or opinion

Class III Evidence and/or general opinion that usefulness/effectiveness does not exist and may be harmful.

LOE A Derived from multiple RCTs

LOE B Derived from a single RCT or nonrandomized studies

LOE C Expert opinion or case series

AHA/ASA = American Heart Association/American Stroke Association

RCT = Randomized Clinical Trial

LOE = Level Of Evidence

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STROKE Recommendations for Evaluation, Treatment, and Secondary Prevention (Kaiser N-

CAL, March 2015) ENDORSED BY Chiefs of Emergency Medicine Chiefs of Medicine Chiefs of Hospital Medicine Chiefs of Neurology Chiefs of Radiology Chiefs of Cardiology Chiefs of Vascular Surgery Medical Director for Quality and Safety

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STROKE Recommendations for Evaluation, Treatment, and Secondary Prevention (Kaiser N-

CAL, March (2015) ACUTE CARE & SECONDARY PREVENTION TEAM MEMBERS

Jai Cho, MD Neurology, Santa Clara, Clinical Lead Alexander C. Flint, MD Neuroscience, Redwood City Jonathan Hartman, MD Neurological Surgery, Sacramento Jina Janavs, MD Neurology, Fremont/Hayward Jeff Klingman, MD Neurology, Walnut Creek Mai Nguyen-Huynh, MD Neurology, Walnut Creek

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TPMG Clinical Stroke Guidelines (March,2015)

KP Northern California has adopted the recommendations from the 2013 AHA/ASA Guidelines for the Early Management of Patients with Acute Ischemic Stroke and the 2014 AHA/ASA Guidelines for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack, unless otherwise noted.

References and additional AHA/ASA Guidelines supporting our recommendations can be found on the Stroke Portal and linked within the guideline on the KPNC Clinical Library at:

https://clm.kp.org/pkc/ncal/clib/guidelines/cpg/Stroke_portal/index.htm

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What is the Evidence ?

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Risk Factors and Stroke MechanismCase #1: 60 year old male awakens from sleep around 1 am following watching the Golden State Warriors and Cleveland Cavaliers NBA Championship (Game #3). He stands up and drops his beer can out of his hand and falls to the floor without injury attempting to go the bathroom. Balance was impaired and he continued to drag his left leg. There was no speech disturbance, confusion , vision impairment ,sensory disturbance, or headache.

Takes no medications.

Pre notification Stroke Alert called and he is brought in by ambulance to Kaiser SRF E.D. -Room 3.

Last known normal at end of game which was 11: 00 pm.

No TPA given as his left leg ataxia was not limiting his walking.

NIHSS- 1 ( left lower leg ataxia). ABCD2 score of 4. Initial BP (ER): 160/92. No A.fib on monitor. BMI- 40%.

Head CT- old right sub-cortical lacunar infarct; Carotid US- 50-69% Left I.C.A. stenosis.

Hospital evaluation: a. No atrial fibrillation on telemetry x 24 hours

b. Brain MRI- no Diffusion Weighted Imaging changes; 2 old lacunar infarcts and mild microvascular disease.

c. Fasting LDL- 160; Fasting Blood Sugar- 112 (A1C% of 6.4)

d. BP in hospital- 140-164/ 84-9611

Cardiac vs Atherosclerotic Disease

Case #2 70 year old female with cardiac pacemaker (h/o 3rd degree heart block) and HTN noticed abrupt onset of expressive speech disturbance and “confusion” lasting 40 minutes around 3 pm today . No fall, headache,vision disturbance,vertigo,paresis or gait difficulty. Drove herself in to Kaiser SRF E.D. for evaluation.

Stroke alert not called as event happened 2 hours previously with well defined normalcy in patient’s and ED MD’s view.

Carotid US done in E.R.- mild atherosclerosis> less 50%- (L)-Internal Carotid ArteryHead CT- normal.

ER BP: 142/92. Heart rate : 112; NIHSS-0; ABCD(2)- 4

Takes 81 mg ASA daily, Lisinopril 20mg a day, Atorvastatin 40mg a day.

Admitted for Observation:

A.Brain MRI- not done (pacemaker)- did not feel study would change management.

B.BP- held Lisinopril > BP 140-150s systolic and HR in 80-90’s (atrial fib).

C. Fasting LDL- 80; FBS- 94, A1C%- 5.812

Cryptogenic StrokeCase #356 yo female with history of migraine with aura since adolescence, BMI% 32, non smoker and no history of HTN,dyslipidemia,diabetes nor any personal or family history of cerebrovascular ,autoimmune or hypercoaguable disorders. Only medications include imitrex or maxalt (infrequent use). Last migraine 1 month ago.

Awoke from sleep in morning at 6 am with left arm heaviness and numbness with difficulty walking. Last known well at 1 am when went to sleep. 911 > BIBA to SRF ED (3). Stroke alert called.

Initial NIHSS of 4 (1 for dysarthria,1 for left arm and leg drift, 1 for sensory extinction on left).

ED- BP (130/80), pulse of 80-regular, Head CT-negative, CTA (head/neck)- no Large Vessel Occlusion and no signs of vasculitis or atherosclerosis. Monitor: no afib.

Admission:

Relevant labs: LDL- 100, HDL- 42, FBS-94,A1C% of 5.8, cbc with diff- wnl

PT/INR,PTT- wnl, ANA- normal, hypercoagulable testing (pending)

2. Cardiac: TTE- PFO without atrial septal aneurysm. TEE- consistent with TTE

3. Brain MRI- right sided (acute) single cortical infarct; no white matter disease.

4. Pelvic CT- no DVT; Lower Extremity Dopplers: wnl.14

Hypertension- Initiation of BP therapy is indicated for previously untreated patients with ischemic stroke or TIA who, after the first several days, have an established BP ≥140 mm Hg systolic or ≥90 mm Hg diastolic . (Class I; Level of Evidence B). - Initiation of therapy for patients with BP <140 mm Hg systolic and <90 mm Hg diastolic is of uncertain benefit . (Class IIb; Level of Evidence C).

- For patients with a recent lacunar stroke, it might be reasonable to target a systolic BP of <130 mm Hg (Class IIb; Level of Evidence B).

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Dyslipidemia1. High Intensity Statin therapy with intensive lipid-lowering effects is

recommended to reduce risk of stroke and cardiovascular events among patients with ischemic stroke or TIA presumed to be of atherosclerotic origin regardless of recent LDL level.

A. Atorvastatin (Lipitor)- 40-80 mg a day. B. Rosuvastatin (Crestor)- 20-40 mg a day.

2. Patients with ischemic stroke or TIA and other comorbid ASCVD should be otherwise managed according to the ACC/AHA 2013 guidelines, which include lifestyle modifications and dietary recommendations (DASH Diet).

(Class I; Level of Evidence A).

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High vs Medium Intensity Statins

High: (Lowers LDL-C by greater than 50%).1.Atorvastatin (40-80 mg) 2.Rosuvastatin (20-40 mg)

Medium: (Lower LDL-C by 30 to 50%).1.Atorvastatin (10-20 mg)2.Rosuvastatin ( 5-10 mg)3.Simvastatin ( 20-40mg)4.Pravastatin (40-80mg)5.Lovastatin (40 mg)6.Fluvastatin (40 mg PO BID)7.Pitavastatin (2-4 mg)Stone NJ et al, American Journal Cardiology ,2013

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Blood Sugar Control

After a TIA or ischemic stroke, all patients should probably be screened for DM with testing of fasting plasma glucose, HbA1c, or an oral glucose tolerance test. (Class IIa; Level of Evidence C).

There is no optimal A1C% that is a goal target specifically for stroke reduction.

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Obesity1. All patients with TIA or stroke should be screened for obesity with measurement of BMI.

(Class I; Level of Evidence C).

2. The usefulness of weight loss among patients with a recent TIA or ischemic stroke and obesity is uncertain (Class IIb; Level of Evidence C).

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Physical Activity For patients who are able and willing to initiate increased physical activity, referral to comprehensive, behaviorally oriented program is probably recommended

(Class IIa; Level of Evidence C).

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Nutrition1. Look for signs of under or over nutrition and refer as appropriate for nutrition counseling.


2 . Routine supplementation with a single vitamin or combination of vitamins is not recommended

(Class III; Level of Evidence A).

3. Reduce Sodium intake to less than 1.5 grams/day to lower blood pressure.


4. Follow a Mediterranean-type diet instead of a low-fat diet. The Mediterranean-type diet emphasizes vegetables, fruits, and whole grains and includes low-fat dairy products, poultry, fish, legumes, olive oil, and nuts. It limits intake of sweets and red meats.


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Sleep Apnea

Consider screening for Sleep Apnea for patients with an ischemic stroke or TIA on the basis of the very high prevalence of sleep apnea in this population.

(Class IIb; Level of Evidence B).

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Carotid Disease1. CAS (Carotid Artery Stenting) is indicated as an alternative to CEA (Carotid Endarterectomy) for symptomatic patients at average or low risk of complications associated with endovascular intervention when the diameter of the lumen of the internal carotid artery is reduced by >70% by noninvasive imaging or >50% by catheter-based imaging or noninvasive imaging with corroboration and the anticipated rate of periprocedural stroke or death is <6%.

(Class IIa; Level of Evidence B).

2. It is reasonable to consider patient age in choosing between CAS and CEA. For older patients (ie, older than ≈70 years), CEA may be associated with improved outcome compared with CAS, particularly when arterial anatomy is unfavorable for endovascular intervention. For younger patients, CAS is equivalent to CEA in terms of risk for peri procedural complication (ie, stroke, MI, or death) and long-term risk for ipsilateral stroke


3. CAS and CEA in the above settings should be performed by operators with established peri procedural stroke and mortality rates of <6% for symptomatic patients, similar to that observed in trials comparing CEA to medical therapy and more recent observational studies.

(Class I; Level of Evidence B).

4. Routine, long term follow-up imaging of the extracranial carotid circulation with carotid duplex ultrasonography is not recommended

(Class III; Level of Evidence B).

5. For patients with recurrent or progressive ischemic symptoms ipsilateral to a stenosis or occlusion of a distal (surgically inaccessible) carotid artery, or occlusion of a mid cervical carotid artery after institution of optimal medical therapy, the usefulness of EC/IC bypass is considered investigational .

(Class IIb; Level of Evidence C).

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Intracranial AtherosclerosisA. For severe stenosis (70%–99%)of a major intracranial artery, consider adding (Plavix) clopidogrel 75 mg/d to aspirin for 90 days might be reasonable.


B. For patients with a stroke or TIA attributable to 50% to 99% stenosis of a major intracranial artery, maintenance of systolic BP below 140 mm Hg and high-intensity statin therapy are recommended.

(Class I; Level of Evidence B)

C. For patients with a stroke or TIA attributable to moderate to severe stenosis (50%–99%) of a major intracranial artery, angioplasty or stenting is not recommended given the low rate of stroke on medical management and the inherent peri procedural risk of endovascular treatment

(Class III;Level of Evidence B).

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Atrial FibrillationA. Atrial Fibrillation for patients who have experienced an acute ischemic stroke or TIA with no other apparent cause, prolonged rhythm monitoring (≈30 days) for AF is reasonable within 6 months of the index event. (Class IIa; Level of Evidence C)

B.VKA therapy (Warfarin/Coumadin) (Class I; Level of Evidence A) Apixaban (Class I; Level of Evidence A) Dabigatran (Class I; Level of Evidence B) Rivaroxiban (Class IIa, Level of Evidence B) are all indicated for the prevention of recurrent stroke in patients with nonvalvular AF, whether paroxysmal or permanent.

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Atrial Fibrillation

A. Can use daily ASA 81 to 325 mg/day) in addition to Warfarin or Novel Oral Anticoagulant for all patients after ischemic stroke or with clinically apparent CAD, particularly an acute coronary syndrome or stent placement


B. For patients unable to take oral anticoagulants, ASA (325 mg/day) alone is recommended.


C. For most patients with a stroke or TIA in the setting of AF initiate oral anticoagulation within 14 days of CVA/TIA.


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Atrial FibrillationA. In the presence of high risk for hemorrhagic conversion (ie, large

infarct, hemorrhagic transformation on initial imaging, uncontrolled hypertension, or hemorrhage tendency), itis reasonable to delay initiation of oral anticoagulation beyond 14 days.

(Class IIa; Level of Evidence B)

B. The usefulness of closure of the left atrial appendage with the

WATCHMAN device in patients with ischemic stroke or TIA and AF is uncertain.


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Valvular Heart Disease

A. Rheumatic mitral valve disease and AF, long term VKA therapy with an INR target of 2.5 (range, 2.0–3.0) is recommended.


B. Rheumatic mitral valve disease without AF, may consider warfarin rather than antiplatelet therapy.


C. For patients with rheumatic mitral valve disease who have an ischemic stroke or TIA while being treated with adequate VKA therapy, the addition of aspirin might be considered.

(Class IIb;Level of Evidence C).

D. Native Aortic or mitral valve disease without AF, antiplatelet therapy is recommended.


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Prosthetic Heart ValveA. For Mechanical Aortic Valve, VKA (Vitamin K antagonist) therapy is recommended with an INR target of 2.5 (range, 2.0–3.0)

(Class I;Level of Evidence B).

B. For Mechanical Mitral valve and a history of ischemic stroke or TIA before its insertion, VKA therapy is recommended with an INR target of 3.0 (range, 2.5–3.5)

(Class I;Level of Evidence C).

C. For patients with a mechanical mitral or aortic valve who have a history of ischemic stroke or TIA before its insertion and who are at low risk for bleeding, the addition of aspirin 75 to 100 mg/d to VKA therapy is recommended.

( Class I; Level of Evidence B).

D. Patients with bioprosthetic aortic or mitral valve, a history of ischemic stroke or TIA before its insertion, and no other indication for anticoagulation therapy beyond 3 to 6 months from the valve placement, long-term therapy with aspirin 75 to 100 mg/d is recommended in preference to long-term anticoagulation


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Antiplatelet TherapyA.For High Risk TIA (ABCD2 score 4 or greater) and any stroke, the combination of ASA (81-162 mg/day) and Clopidogrel (75 mg/day) might be considered for initiation within 24 hours of a minor ischemic stroke or TIA and for continuation of 90 days.

CHANCE STUDY (CHINA)

POINT TRIAL (ONGOING in USA).


A.For patients with a history of ischemic stroke or TIA, AF, and CAD, the usefulness of adding antiplatelet therapy to VKA therapy is uncertain for purposes of reducing the risk of ischemic cardiovascular and cerebrovascular events.


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Aortic Arch Atheroma(s)

A. For patients with an ischemic stroke or TIA and evidence of aortic arch atheroma, antiplatelet therapy is recommended. (Class I; Level of Evidence A).B. For patients with an ischemic stroke or TIA and evidence of aortic arch atheroma, statin therapy is recommended. (Class I; Level of Evidence B).

NO PRESENT EVIDENCE FOR USE OF ANTICOAGULANTS or SURGICAL ENDARECTOMY.

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Patent Foramen Ovale (PFO)

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A. For ischemic stroke or TIA and a PFO, antiplatelet therapy is recommended

(Class I; Level of Evidence B).

B. For patients with an ischemic stroke or TIA and both a PFO and a venous source of embolism, anticoagulation is indicated, depending on stroke characteristics.


C. When anticoagulation is contraindicated, an inferior vena cava filter is reasonable.


D. For cryptogenic ischemic stroke or TIA and a PFO without evidence for DVT, available data do not support a benefit for PFO closure.

(Class III; Level of Evidence A).

E. In the setting of PFO and DVT, PFO closure by a transcatheter device might be considered, depending on the risk of recurrent DVT.


Case #1- Management and Long Term Risk Reduction

A. Hypertension: start ACE Inhibitor, Calcium Channel Blocker or Diuretic with outpatient BP checks consistently and daily over coming weeks.

Goal BP under 130/90.B. Statin: check baseline ALT and begin High Intensity Statin such as

Atorvastatin (40-80 mg a day)- other options (Rosuvastatin 20-40 mg a day).

Recheck Fasting Lipid Panel in 2-3 months> goal LDL under 80 and preferably 50% reduction of LDL level.

C. Nutrition: DASH Diet- low sodium (under 1.5 grams per day) with focus on Fruits/Vegetables as described in Mediterranean lifestyle concept.

D. Exercise: 30-45 minutes (moderate aerobic exercise)- jogging or equivalent to get Heart Rate to aerobic zone (220-age= # x 0.65%) 5 days per week or equivalent of 150 minutes of exercise a week.

E. 81 to 162 mg ASA OR 3 weeks of 75 mg Clopidrogrel and 81-162 mg ASA followed by Clopidrogrel monotherapy (75 mg a day).

F. Obstructive Sleep Apnea screen.G. Repeat FBS/A1C% in 2-3 months.

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CHANCE STUDYClopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic AttackN Engl J Med 2013; 369:11-19July 4, 2013Results: Stroke occurred in 8.2% of patients in the clopidogrel–aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel–aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group

Conclusions:Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage

Treatment: Clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days.

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http://www.nejm.org/toc/nejm/369/1/


A. Hypertension: Restart Lisinopril and may have to increase dose to 40 mg a

Day with outpatient daily monitoring over coming weeks. ( check potassium and creatinine levels).

Goal BP under 130/90 long term.

B. Statin: check baseline ALT and continue High Intensity Statin such as Atorvastatin increasing to 60 mg a day.

C. Recheck Fasting Lipid Panel in 2-3 months> goal LDL under 70 mg/dl and 50% reduction of LDL level.

C. Nutrition: DASH Diet- low sodium (under 1.5 grams per day) with focus on Fruits/Vegetables as described in Mediterranean lifestyle concept.

D. Exercise: 30-45 minutes (moderate aerobic exercise)- jogging or equivalent to get Heart Rate to aerobic zone (220-age= # x 0.65%) 5 days per week or equivalent of 150 minutes of exercise a week.

E. Start 325 mg ASA orally with Coumadin (INR goal 2.0 to 3.0) and stop ASA when INR is > 2.0 or Novel Oral Anticoagulant such as Pradaxa.

F. Follow up Carotid Ultrasound in 6-12 months (re examine Left I.C.A.)

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Anticoagulation After Cardioembolic Stroke: To Bridge

or Not to Bridge?• Hen Hallevi, MD,1 Karen C. Albright, DO, MPH,3 Sheryl

Martin-Schild, MD, PhD,1 Andrew D. Barreto, MD,1 Sean I. Savitz, MD,1 Miguel A. Escobar, MD,2 Nicole R. Gonzales, MD,1 Elizabeth A. Noser, MD,1 Kachi Illoh, MD,1 and James C. Grotta, M

Arch Neurol. 2008 Sep; 65(9): 1169–1173.

Conclusion: Anticoagulation of patients with cardio embolic stroke can be safely started with warfarin shortly after stroke. Heparin bridging and enoxaparin bridging increase the risk for serious bleeding

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A. Hypertension: Consider low dose ACE inhibitor , Diuretic or Calcium Channel blocker.

This recommendation is based upon observations in randomized trials, such as PROGRESS, that the relative risk reduction in stroke with antihypertensive therapy was similar at all levels of baseline systolic pressure (ranging from <120 to ≥160 mmHg).

Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial. AUArima H, Chalmers J, Woodward M, Anderson C, Rodgers A, Davis S, Macmahon S, Neal B, PROGRESS Collaborative GroupSO J Hypertens. 2006;24(6):1201.

Goal BP under 130/90 long term.

B. Statin: check baseline ALT and start High Intensity Statin such as Atorvastatin (40-80) mg a day.

-Recheck Fasting Lipid Panel in 2-3 months> goal LDL under 70 mg/dl and 50% reduction of LDL level.

C. Exercise: 30-45 minutes (moderate aerobic exercise)- jogging or equivalent to get Heart Rate to aerobic zone (220-age= # x 0.65%) 5 days per week or equivalent of 150 minutes of exercise a week.

D. Start 325 mg ASA orally with Coumadin (INR goal 2.0 to 3.0) and stop ASA when INR is > 2.0 or long term Novel Oral Anticoagulant such as Pradaxa.

E Long term monitoring session for atrial fibrillation detection.

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Thanks for Helping

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REDUCE STROKE RISK

stroke symposium talk on secondary prevention

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