Update’Guidelines’for’Secondary’ Stroke’Preven7on’2014’hoidotquyvietnam.com/upload/images/Update guideline 2014.pdf · Update’Guidelines’for’Secondary’ Stroke’Preven7on’2014’

Update Guidelines for Secondary

Stroke Preven7on 2014

Nguyen Huy Thang, MD

Cerebrovascular Disease Department

The People ‘s 115 Hospital

Hospital-‐based surveillance of stroke over 12 months in People ‘s 115 Hospital 2010

Pham Lan Tran, Nguyen Huy Thang, Velandai Srikanth. Paper in prepara7on

Secondary PrevenEon in AtheroscleroEc Ischemic Stroke

Aspirin

Aspirin plus

Statin

ACE

Diabetes

Indicated Probably Indicated May consider Not Indicated

Recommended Targets for Secondary Stroke Preven7on

Blood pressure Ischemic stroke, TIA < 140/90 mm Hg DM, renal failure, hemorrhagic stroke < 130/80 mm Hg

Glycaemic control

HbA1C < 7.0% Preprandial plasma glucose 5.0-‐7.2 mmol/L (90-‐130 mg/dL) Peak postprandial plasma glucose < 10.0 mmol/L (180 mg/dL)

Lipids

LDL-‐Cholesterol -‐ Ischemic stroke, TIA < 100 mg/dL -‐ Recurrent ischemic strokes, < 70 mg/dL significant vascular stenosis/occlusion, concurrent IHD and/or PVD AHA Guidelines 2011

Outline

•  Hypertension

•  Diabetes

•  Hyperlipidemia

•  Minor stroke & TIA

•  Blood pressure reduc7on is recommended in

persons who have had an ischemic stroke or

TIA are beyond the first 24 hours with

neurological symptoms stable.

(Class I; Level of Evidence A)

Stroke. 2011;42:227-‐276.

•  Ini7a7on of BP therapy is indicated for previously untreated pa7ents with IS or TIA who, a^er the first several days, have an established BP ≥140 mm Hg systolic or ≥90 mm Hg diastolic

(Class I; Level of Evidence B). •  Ini7a7on of therapy for pa7ents with BP <140 mm Hg systolic and <90 mm Hg diastolic is of uncertain benefit (Class IIb; Level of Evidence C).

Clarifica7on of parameters for ini7a7ng BP therapy

AHA/ASA Guidelines for Stroke 2014

10 mmHg lower SBP 28% stroke risk 5 mm Hg lower DBP 33% stroke risk

BMJ. 1996; 313: 147 The trial included 2435 people from 33 centres

•  Bao gồm 6105 BN có 7ền sử ĐQ hay TIA, lựa chọn

ngẫu nhiên Perindopril 4mg (+ Indapamide) hoặc

Placebo.

•  40% BN có mức huyết áp < 140/ 90 mmHg

•  Tiêu chí kết quả chính: đột quỵ tử vong và không tử vong

PROGRESS -‐ Lancet 2001; 358: 1033–41

Blood Pressure Lowering

9 mmHg

4 mmHg

Progress. Lancet 2001; 358: 1033

Primary Endpoint Result

28%

Lancet 2003;358: 1033

Be{er Outcomes with ACE & Diure7c

•  SPS3 enrolled 3020 pa7ents with lacunar to 2 different target levels of SBP control, <150 versus <130 mmHg.

•  Mean 7me from qualifying event to randomiza7on was 62 days. At baseline, mean SBP was 145 mm Hg in the higher-‐target group and 144 mm Hg in the lower-‐target group.

NEJM 2012 367;9

Lacunar Infarct

Systolic BP <150 mmHg <130 mmHg

12 months 138 mm Hg 127 mm Hg Recurrent stroke 2.8 % 2.3 %

Ischemic stroke 2.4 % 2.0 %

HR 16 %

Hemorrhagic stroke 0.29 % 0.11 %

HR 63%

HR 21 %


•  Goals for target BP level or reducEon from pretreatment baseline are uncertain and should be individualized, but it is reasonable to achieve a systolic pressure <140 mm Hg and a diastolic pressure <90 mm Hg

(Class IIa; Level of Evidence B). •  For paEents with a recent lacunar stroke, it might be reasonable to target an SBP of <130 mm Hg

(Class IIb; Level of Evidence B).

•  The op7mal drug regimen to achieve the recommended level of reduc7ons is uncertain because direct comparisons between regimens are limited.

•  The available data indicate that diure7cs or the combina7on of diure7cs and an angiotensin-‐conver7ng enzyme inhibitor is useful.

(Class I; Level of Evidence A).


Outline

•  Hypertension

•  Diabetes


•  Minor stroke and TIA

•  Use of exis7ng guidelines from the ADA for glycemic control and cardiovascular risk factor management is recommended for pa7ents with an ischemic stroke or TIA who also have DM or pre-‐DM (Class I; Level of Evidence B).

•  Randomized clinical trial evidence among high-‐risk pa7ents with DM indicates that there

is no benefit in achieving an aggressive SBP of <120 versus <140 mm Hg

N Engl J Med. 2010;362:1575–1585


•  A^er a TIA or ischemic stroke, all pa7ents should probably be screened for DM with tes7ng of fas7ng plasma glucose, HbA1c, or an oral glucose tolerance test. In general, HbA1c may be more accurate than other screening tests in the immediate postevent period

(Class IIa; Level of Evidence C).


Outline

•  Hypertension

•  Diabetes



Potential Mechanisms of Benefit

LDL Reduction

Plaque stabilization: macrophages smooth muscle cells immunologic response lipid core oxidized LDL

Improved endothelial function Reduced hemorheologic stress Reduced platelet aggregation Reduced thrombotic and Enhanced fibrinolytic state

Statin

Blood pressure reduction Decrease incidence of MI and of left ventricular mural thrombus

35 to 80% of the benefit

Neuroprotection . Up-regulation NO . Improves CBF . Reduces infarct size

METEOR

•  METEOR used B-‐mode ultrasound to evaluate

whether (rosuvasta7n) treatment of

subclinical atherosclerosis can slow

progression and/or cause regression

Crouse JR III, et al. JAMA 2007 297:1344-1353

internal carotid artery common carotid artery

carotid bulb

carotid dilatation

external carotid artery carotid flow divider

Measuring IMT probe

blood flow

Caro7d IMT Measured Using B-‐mode Ultrasound

Example for an individual subject from METEOR

Detail showing IMT measurement Ultrasound Image of the Carotid Artery

METEOR -‐ Pa7ent Flow 5751 subjects screened for Lipids, CV risk and

CIMT; 984 Randomized

Rosuvastatin 40mg n=702

Placebo n=282

ITT n=624

Completed 2 year follow-up

n=530

ITT n=252

Completed 2 year follow up

n=208

No follow up CIMT

Discontinued later

N = 78 N = 30

N = 94 N = 44

Crouse JR, et al. JAMA 2007 297:1344-1353

METEOR primary endpoint:

Rate of change of maximum IMT at 12 caro7d sites

Left Right

Internal

Bulb

Common Time M

axim

um I

MT

For each segment

The maximum IMT at each of the 12 carotid sites is measured over

2 years. The rate of change is calculated.

Crouse JR et al. Cardiovasc Drugs Ther 2004; 18: 231–238

Time (years)

Cha

nge

in I

MT

of 1

2 ca

rotid

site

s (m

m)

-0.01

+0.01

0.00

+0.02

2 1

+0.03

Prog

ress

ion

Regr

essi

on

Rosuvastatin vs. zero slope

Placebo +0.0131 mm/yr

(n=252)

Rosuvastatin 40 mg -0.0014 mm/yr

(n=624)

P<0.001 (Rosuvastatin vs. placebo)

Placebo; Change in CIMT (95% CI)

Rosuvastatin 40 mg; Change in CIMT (95% CI)

Rate of change of maximum IMT at 12 caro7d sites Rosuvasta7n vs placebo

Crouse JR, et al. JAMA 2007 297:1344-1353

LDL-‐C Lowering and Stroke

1.2 1.2 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0

0 -‐10 -‐15 -‐20 -‐25 -‐30 -‐35 -‐40 -‐45 -‐50 -‐55

ALLIANCE

ALL-‐HAT LLT SEARCH

GISI

A TO Z MEGA

IDEAL LIPID

TNT

WOSCOPS ASPEN

PREOVE-‐IT

PROSPER

Post-‐CABG

AFCAPS-‐TexCAPS

HPS

ASCOT-‐LLA

CARE SSSS

SPARCL

CARDS GREACE MIRACL

JUPITER

Between group differences in LDL-‐C reducEon (% acEve minus control groups)

RelaEv

e risk of stroke in acEve vs. con

trol group

s All Trials Secondary PrevenEon

Per 10% LDL-‐C ReducEon RRR Primary PrevenEon = 13.5% (7.7-‐18.8%) RRR overall = 7.5% (2.3-‐12.5%)

n= 165, 792

Each 1 mmol (39 mg) LDL-‐C reducEon reduced the risk of stroke by 21% (95% CI 6.3 to 33.5%, p<0.001)

Amarenco P, Labreuche J. Lancet Neurol. 2009; 8:453-‐63

4,731 Patients

SPARCL: Study Design

Placebo

540 Primary Endpoints

Atorvastatin 80 mg/day

Double-Blind Period

Source: The SPARCL Investigators. Cerebrovasc Dis. 2003;16:389–395

Primary End Point Time to the First Occurrence of a Fatal or Nonfatal Stroke

Patient Population

w  205 sites worldwide

w Previously documented stroke or TIA within 6 months

w No history of CHD

w  LDL-C levels ≥100 mg/dL and ≤190 mg/dL

0

20

40

60

80

100

120

140

Baseline Month 3 Year 1 Year 3 Year 5 Last

Timepoint

Mea

n (m

g/dL

)LDL-‐C During Follow-‐up

Mean on-treatment LDL-C: Placebo = 129 mg/dL Atorvastatin = 73 mg/dL

-53%

+1%

-7%

-38%

Baseline LDL-C: 133 mg/dL

Amarenco P, Bogousslavsky J, Callahan A III, et al. N Engl J Med. 2006;355:549-59

Primary Endpoint: Time to Fatal or Non-‐Fatal Stroke

Adjusted HR (95% CI)* = 0.84 (0.71, 0.99), p = 0.03

16% RR

Years Since Randomization

Fata

l or N

on-F

atal

Str

oke

(%)

0 1 2 3 4 5 6 0%

4%

8%

12%

16%

Placebo Atorvastatin

* Treatment effect from Cox proportional hazards models with pre-specified adjustment for geographical region, entry event, time since entry event, gender, and baseline age.

Amarenco P, Bogousslavsky J, Callahan A III, et al. N Engl J Med. 2006;355:549-59

•  Sta7n therapy with intensive lipid-‐lowering effects is recommended to reduce risk of stroke and cardiovascular events among pa7ents with ischemic stroke or TIA presumed to be of atherosclero7c origin and an LDL-‐C level ≥100 mg/dL with or without evidence for other clinical ASCVD

(Class I; Level of Evidence B) (Revised recommendaQon)


•  Sta7n therapy with intensive lipid-‐lowering effects is recommended to reduce risk of stroke and cardiovascular events among pa7ents with ischemic stroke or TIA presumed to be of atherosclero7c origin and an LDL-‐C level <100 mg/dL and no evidence for other clinical ASCVD

(Class I; Level of Evidence C) (New recommendaQon)


“ It is reasonable to target a reducEon of at least 50% in

LDL-‐C or a target LDL-‐C level of < 70 mg/dL to obtain

maximum benefit ”

(Class IIa; Level of Evidence B)

(New recommendaQon)

Outline

•  Hypertension

•  Diabetes



5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin(clopidogrel at an ini7al 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) or to placebo plus aspirin (75 mg per day for 90 days)

N Engl J Med 2013;369:11-19.

Primary Outcomes

N Engl J Med 2013;369:11-19.

The primary outcome of ischemic or hemorrhagic stroke was observed in 8.6% of par7cipants assigned to combina7on therapy compared with 11.7% assigned to aspirin monotherapy

(HR, 0.68; 95% CI, 0.57–0.81).

The combina7on of aspirin and clopidogrel

might be considered for ini7a7on within 24

hours of a minor ischemic stroke or TIA and for

con7nua7on for 90 days

(Class IIb; Level of Evidence B).

New recommenda7on

Small vessel disease

Large artery disease

Undetermined Causes

STROKE CLASSIFICATION Cardioembolism

15-‐25%

30-‐40%

10-‐20%

30-‐40%

RECURRENCE STROKE IS HIGHEST WITH LARGE VESSEL DISEASE

Stroke 2003; 31: 1062

Extracranial CaroEd Disease RecommendaEons

For paEents with a TIA or ischemic stroke within the

past 6 months and ipsilateral severe (70%–99%)

caroEd artery stenosis as documented by noninvasive

imaging, CEA is recommended if the perioperaEve

morbidity and mortality risk is esEmated to be <6%

(Class I; Level of Evidence A).

For paEents with recent TIA or ischemic stroke and ipsilateral moderate (50%–69%) caroEd stenosis as documented by DSA,CTA, or MRA. CEA is recommended depending on paEent-‐specific factors, such as age, sex, and comorbidiEes, if the perioperaEve morbidity and mortality risk is esEmated to be <6% (Class I; Level of Evidence B). When the degree of stenosis is <50%, CEA and CAS are not recommended (Class III; Level of Evidence A).

CAS is indicated as an alterna7ve to CEA for

symptoma7c pa7ents at when the diameter of the

lumen of the ICA is reduced by >70% by noninvasive

imaging or >50% by DSA and the an7cipated rate of

periprocedural stroke or death is <6%

(Class IIa; Level of Evidence B).

(Revised recommendaQon)

•  It is reasonable to consider pa7ent age in choosing between CAS and CEA. For older pa7ents (ie,older than ≈70 years), CEA may be associated with improved outcome compared with CAS, par7cularly when arterial anatomy is unfavorable for endovascular interven7on. For younger pa7ents, CAS is equivalent to CEA in terms of risk for periprocedural complica7on (ie, stroke,MI, or death) and long-‐term risk for ipsilateral stroke

Class IIa; Level of Evidence B (New recommendaQon)


Op7mal medical therapy, which should include

anEplatelet therapy, staEn therapy, and risk factor

modificaEon, is recommended for all pa7ents with

caro7d artery stenosis and a TIA or stroke, as outlined

elsewhere in this guideline (Class I; Level of Evidence A).

•  Bao gồm 451/ 764 Bn đột quỵ/ TIA có hẹp 70-‐99% ĐM nội

sọ tại 50 trung tâm Đột quỵ tại Hoa Kỳ.

•  Lựa chọn ngẫu nhiên điều trị nội khoa & đặt stent kèm

theo điều trị nội khoa sau đó.

•  Kết quả chính: tỷ lệ ĐQ/ tử vong trong 30 ngày

SAMMPRIS Trial. NEJM 2011

•  Stroke & Vascular Death/ 30 days •  Medical Treatment Stent

5.8% 14.7% p 0.002

•  Ischemic Stroke in territory of qualifying artery > 30 days

•  13 (5.7%) 13 (5.8%) NS

AGGRESSIVE MEDICAL MANAGEMENT

WASID SAMMPRIS

Antiplatelet ASA 325mg ASA 325mg + Clopidogrel 75mg

(3 tháng)

Sta7n No Rosuvasta7n LDL < 70 mg%

Risk factors control

SBP < 140mmHg

< 130 mmHg with DM

For pa7ents with a stroke or TIA a{ributable to moderate stenosis (50%–69%) of a major intracranial artery, angioplasty or sten7ng is not recommended given the low rate of stroke on medical management and the inherent periprocedural risk of endovascular treatment (Class III; Level of Evidence B). For pa7ents with stroke or TIA a{ributable to severe stenosis (70%–99%) of a major intracranial artery, sten7ng with the Wingspan stent system is not recommended as an ini7al treatment, even for pa7ents who were taking an an7thrombo7c agent at the 7me of the stroke or TIA (Class III; Level of Evidence B).

New recommenda7on

For pa7ents with recent stroke or TIA (within 30 days) a{ributable to severe stenosis (70%–99%)of a major intracranial artery, the addi7on of clopidogrel 75 mg/d to aspirin for 90 days might be reasonable (Class IIb; Level of Evidence B). For pa7ents with stroke or TIA a{ributable to 50% to 99% stenosis of a major intracranial artery, the data are insufficient to make a recommenda7on regarding the usefulness of clopidogrel alone, the combina7on of aspirin and dipyridamole, or cilostazol alone (Class IIb; Level of Evidence C). For pa7ents with a stroke or TIA a{ributable to 50% to 99% stenosis of a major intracranial artery, maintenance of systolic BP below 140 mm Hg and high-‐intensity sta7n therapy are recommended (Class I; Level of Evidence B).

New recommenda7on

Best Therapy for Extracranial Stenose

Aspirin + Clopidogrel + High dose of Sta7n (First month) CEA or CAS when symptoma7c & significant stenose And then: Aspirin Clopidogrel Aspirin plus Dipyridamole Cilostazol

Control of systolic BP below 140 mmHg and DM

Best Therapy for Intracranial Stenose

Aspirin + Clopidogrel + High dose of Sta7n (First month) And then: Aspirin Clopidogrel Aspirin plus Dipyridamole Cilostazol

Control of systolic BP below 140 mmHg and DM

Documents

Update’Guidelines’for’Secondary’ Stroke’Preven7on’2014’hoidotquyvietnam.com/upload/images/Update guideline 2014.pdf · Update’Guidelines’for’Secondary’ Stroke’Preven7on’2014’