Acute Stroke Management:Lytics and Blood Pressure

A Lunch and Learn TalkOn Behalf of the Colorado Stroke Alliance

6/13/08San Luis Valley Regional Medical Center

Don B Smith, MDStroke Program DirectorSwedish Medical Center

Colorado Neurological Institute

CNI COLORADONEUROLOGICALINSTITUTE

Outline

• General Comments on Stroke• TPA Thrombolysis • Mechanical Thrombolysis• Urgency and Systems of Care• Optional issues (as time permits):

– Blood pressure treatment in acute stroke– Stroke prevention in atrial fibrillation– Stroke prevention with statins– Antiplatelet agents and stroke prevention

• The impact of stroke– Third leading cause of death– Primary cause of long term disability– > 700,000 strokes / year in USA– 15% - 20% are fatal– Disability is the rule among survivors– > $ 50,000,000,000 / year

• In short, common, costly & tragic

General Comments on Stroke

0

10

20

30

40

50

60

19

91

19

92

19

93

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

Year

Str

oke

Art

icle

sInterest in Stroke

(Articles about Stroke in the New York Times)

Heiss et al, Stroke 1999

"Brain Attack"A Process Not an Event

TPA Thrombolysis

38%

50%

23%

16%

18%

17%

21%

17%

Placebo

r-tPA

No Disability Mod Disability Severe Disability Death

Adapted from NEJM: 1995, 333:1581-1588 (Barthel Index Scores)

Median NIHSS = 14; Mean Age ~67; P = 0.008; RRR ~30% , ARR ~12%, NNT~8

Patient Selection for tPA• Ischemic stroke with persistent, significant neurological deficit (NIHSS > 4)• Onset <3 hrs before beginning treatment• Exclusions:

– Head trauma or prior stroke in previous 3 months– Myocardial infarction in the previous 3 months– Gastrointestinal or urinary tract hemorrhage in previous 21 days– Major surgery in the previous 14 days– Arterial puncture at a non-compressible site in the previous 7 days– History of previous intracranial hemorrhage– Blood pressure persistently >185/>110– Active bleeding or acute trauma (fracture) on examination– Oral anticoagulant or if anticoagulant being taken, INR >1.7– Heparin in previous 48 hours, with elevated aPTT– Platelet count <100 000– Hemorrhage on CT– Visible large infarct on CT– Symptoms strongly suggesting subarachnoid hemorrhage

• Beware of mimics– Glucose concentration <50 mg/dL (2.7 mmol/L)– Seizure at onset– Migraine, Bell’s palsy, conversion disorder, peripheral vertigo

• Be sure patient/ family understand potential risks/ benefits

Guidelines for the Early Management of Adults With Ischemic Stroke. Stroke. 2007;38:1655-1711 (Corrections: Stroke 2007;38:e38)

IV tPA Orders: Simple Enough• 0.9 mg/kg (max 90 mg) over 60 min

– 10% of dose given as bolus dose over 1 min

• Neuro assessments– q 15min w/ infusion, q 30 min x 6 hr, q 1hr x 24 hr

• Check BP– q 15 min x 2 hr, q 30 min x 6 hr, q 1 hr x 24 hr

• Watch for signs of ICH– Severe HA, nausea, vomiting, acute HTN– Discontinue tPA infusion and obtain emergent CT

• Delay NG tubes, bladder catheters, IA pressure catheters

Guidelines for the Early Management of Adults With Ischemic Stroke. Stroke. 2007;38:1655-1711 (Corrections: Stroke 2007;38:e38)

t-PA Use for Ischemic Stroke*Colorado, 1999-2001

Year N t-PAIschemic StrokesTreated with t-PA

1999 7739 87 1.12%

2000 7835 89 1.14%

2001 8144 89 1.10%

*Primary Diagnosis = Ischemic Stroke: ICD9 433-438, 997.02

t-PA = ICD9 Proc Code 99.10

Hospital to pay stroke victim $19 mil. March 21, 2007BY JIM RITTER Staff Reporter

Evanston Northwestern Healthcare has agreed to pay $19.5 million to a hedge fund executive after allegedly botching his stroke treatment.

Following his 2005 stroke, Ted Baxter was unable to return as global controller for Citadel hedge funds. Baxter has difficulty speaking and understanding words.

"He loved what he did," said his attorney, David Barry of Corboy and Demetrio.

It's the largest malpractice settlement in Cook County in a case that did not go to trial.

In a statement, Evanston Northwestern said: "We deeply regret the medical outcome that [Baxter] and his wife live with today. We feel strongly that the financial settlement ... appropriately reflects a fair and equitable amount."

Baxter, 41, came to Evanston Hospital's emergency room with stroke symptoms. A resident doctor misread an MRI exam that confirmed the stroke. Consequently, Baxter did not receive the clot-busting drug tPA, which can minimize debilitating effects when given within the first few hours, Barry said.

Throughout the night, Baxter's symptoms continued to get worse, and his wife repeatedly asked that he be examined again but was told to wait until morning. By the next day, Baxter was paralyzed on the right side.

He has learned to walk and use his arm again, thanks to therapy "and sheer force of will," Barry said.

(http://www.suntimes.com/news/metro/305846,CST-NWS-stroke21.article)

Patients Expect More

Mechanical Thrombolysis

Concentric Clot RetrieverEKOS UltrasoundEndicor X-ciserEPAR Laser, LaTIS LaserGooseneck MicrosnareNeuronet Endovascular SnarePossis AngiojetPenumbra Device

Intra-arterial Treatment:PROACT II

0

5

10

15

20

25

30

35

40

45

r-proUK control

% P

atie

nts

wit

h M

odif

ied

R

anki

n S

c or e

≤2

at 9

0 d

ays

P = 0.04ARR = 15%NNT = 6.7

40%

25%

Primary Outcome

Time is a Big Factor

Time

Cer

ebra

l Blo

od F

low

~ 30 cc/100gm/min = symptoms

IrreversibleInfarction

ReversibleIschemia

~ 60 cc/100gm/min = normal

Variations in Circle of Willis

Peripheral Anastamoses

Collateral Circulation Also MattersC

ereb

ral B

lood

Flo

w

Time

MTT CBV

CTA

CT Perfusion

Pt Selection by Advanced Imaging

Caveat Emptor:Devices, Drugs, and the FDA

Stroke 2005;35:400-403

• FDA requires proof of clinical efficacy for drugs, but not for devices.• Surrogate end point (recanalization): OK for devices, not for drugs.• FDA approval skirts the issue of “stroke therapy” by approving devices for “removal of clots,” not “for treatment of stroke.”

Devices and Wall Street

IMS III: Testing the IA Approach

t-PA Use for Ischemic Stroke*Colorado, 1999-2001

Year N t-PAIschemic StrokesTreated with t-PA

1999 7739 87 1.12%

2000 7835 89 1.14%

2001 8144 89 1.10%

*Primary Diagnosis = Ischemic Stroke: ICD9 433-438, 997.02

t-PA = ICD9 Proc Code 99.10

Urgency and Systems of Care

• How Could We Do Better?• Cardiology Experience

– Intravenous thrombolysis works for the heart– Intra-arterial treatment works better

• Trauma Experience– Care in designated centers is beneficial for patients for

whom a complex set of urgent actions must be coordinated among many individuals

Re-Engineering Stroke TreatmentElements of a Primary Stroke Center

• Acute Stroke Teams• Center Director• Educational Programs• Emergency Department• Emergency Medical Services• Laboratory Services• Neuroimaging• Neurosurgical Services• Organizational Support and Commitment• Outcome and Quality Improvement• Stroke Unit• Written Care Protocols

Recommendations for the Establishment of Primary Stroke CentersJAMA, June 21, 2000—Vol 283, 3102-3109

Comprehensive Stroke Centers, 2005

• Carotid US & TCD• CT Angiography• Database/Registry• Digital angiography• Echocardiography• Intravascular Rx

– IA lytics– Mechanical clot extraction– Angioplasty/Stenting– GDC coils

• ICU• MRI/MRA/DWI• Rehabilitation• Stroke Unit

Stroke. 2005;36:1597-1618

Stroke. 2005;36

After Primary and Comprehensive Stroke Centers: Stroke Networks

Patients

N N

CSC CSC

PSC

N N

PSC PSC

Recommendations for Comprehensive Stroke Centers. Stroke. 2005;36:1597-1618

Patients

Patients

Patients

Patients

Patients

Organization of Stroke Centers in a Hospital Network of Geographical Area

Adapted from Marler et al. Neurology 55:1649-1655, 2000

Time is Not On Our SideOdds of Favorable OC at 3 months, c/w Placebo

8

7

6

5

4

3

2

1

060 70 80 90 100 110 120 130 140 150 160 170 180

Minutes from Stroke Onset to Start of Treatment

Od

ds

Rat

io f

or

Fav

ora

ble

Ou

tco

me

at 3

Mo

nth

s

Neuronal loss during stroke is estimated to be

32,000 cells/second

Access to Urgent Stroke Care

Telemedicine

• Site-Independent• Internet-Based• HIPAA Compliant• Synchronized 2-Way A/V• DVD-Quality Video

– 750kbps Video, 44.1kbps Audio

• DICOM Server Integrated• Remotely Controlled

CO-DOC Telemedicine Sites

• Cortez• (Greeley)• Gunnison• Kremmling• North Suburban• Springfield• Trinidad• Vail• Yuma

Colorado

The Colorado Stroke Alliance

• November 2004– Colorado voters pass Amendment 35– Increase tobacco excise taxes– Tax revenues dedicated to health programs

• January 2005– Tax increases go into effect

• June 2006– Funds available for Colorado Stroke Registry

The Strategy:Use individual hospitals’ QI data in the service

of a statewide system of care

Registry Site

Outcome Sciences

Colorado Stroke Alliance

ASA/AHA

GWTG data

1. State-level aggregate data2. Pt-level data, de-identified for:

• Patient, and• Treating hospital

GWTG data

Local & benchmark reports

04/12/23 35

SoutheastColorado

Boulder

Memorial – CoSprngs

St MaryCorwin-Pueblo

Spanish PeaksWalsenburg

Yuma

Keefe Mem

DHMC

UH

Swedish

St A’North

St A’Central Aurora

Littleton

Lutheran

Mt San RafaelTrinidad

NorthCoMedCntr

Parkview-Pueblo

Penrose-CoSprngs

St. Mary Grand Junct

Melissa Memorial.

Haxtun

Prowers – Lamar

MemorialCraig

MemorialCraig

NSMC

Conejos County hosp.

San Luis Valley

Rangely DistHosp

St VincentLeadville

Poudre ValleyFt. Collins

Community Grand Junct

Wray

Summit

CSA site

Patients in Colorado Stroke RegistryAverage through October, 2007 = 173.7 additions/month

0

2000

4000

6000

8000

20

06

_0

6

20

06

_0

8

20

06

_1

0

20

06

_1

2

20

07

_0

2

20

07

_0

4

20

07

_0

6

20

07

_0

8

20

07

_1

0

20

07

_1

2

20

08

_0

2

20

08

_0

4

20

08

_0

6

20

08

_0

8

20

08

_1

0

20

08

_1

2

Year_Month

Cu

mu

lati

ve #

Pat

ien

ts

Actual Exp Fit Linear Fit

Date of Analysis 11/12/07

TPA for Ischemic StrokeTemporal Trends (N = 1787)

0

20

40

60

80

100

120

140

160

20

06

_0

6

20

06

_0

7

20

06

_0

8

20

06

_0

9

20

06

_1

0

20

06

_1

1

20

06

_1

2

20

07

_0

1

20

07

_0

2

20

07

_0

3

20

07

_0

4

20

07

_0

5

20

07

_0

6

20

07

_0

7

20

07

_0

8

20

07

_0

9

20

07

_1

0

20

07

_1

1

20

07

_1

2

0%

2%

4%

6%

8%

10%

12%

14%

16%

#IschemicStrokes %GivenTPA at YourHosp

Overall = 7.5%

Symptomatic ICHWith IV TPA for Ischemic Stroke

Temporal Trends (N = 134)

0

2

4

6

8

10

12

14

20

06

_0

7

20

06

_0

8

20

06

_0

9

20

06

_1

0

20

06

_1

1

20

06

_1

2

20

07

_0

1

20

07

_0

2

20

07

_0

3

20

07

_0

4

20

07

_0

5

20

07

_0

6

20

07

_0

7

20

07

_0

8

20

07

_0

9

20

07

_1

0

20

07

_1

1

20

07

_1

2

0%

10%

20%

30%

40%

50%

60%

#PtGivenTPAatYourHosp %with Sx ICH

Overall = 6.7%

0%

20%

40%

60%

80%

100%

1 2 3 4 5 6 7 8 9 10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

Onset To Arrival (Hours)

% o

f G

rou

p

EMS (1049) WalkIn (593)

Compared with Walk-Ins, ~20% more EMS patients arrive w/in 3 hours

Date of Analysis 12/12/07

Onset to Arrive(For Pts Arriving Within 24 Hours)

N = 1642

Likelihood of IV TPA for Ischemic Stroke Patients, by Arrival Mode

3.2%16.0%0%

20%

40%

60%

80%

100%

EMS (745) Priv (441)

IV TPA No TPA

P <0.001 Chi Square

-200

0

200

400

600

800

1000

1200

20

06

_0

6(1

4)

20

06

_0

7(8

7)

20

06

_0

8(9

4)

20

06

_0

9(8

2)

20

06

_1

0(8

7)

20

06

_1

1(1

02

)

20

06

_1

2(9

8)

20

07

_0

1(1

25

)

20

07

_0

2(1

21

)

20

07

_0

3(1

63

)

20

07

_0

4(1

37

)

20

07

_0

5(1

47

)

20

07

_0

6(1

26

)

20

07

_0

7(1

26

)

20

07

_0

8(1

42

)

20

07

_0

9(1

10

)

20

07

_1

0(5

1)

20

07

_1

1(2

)O

-A (

min

ute

s)

+SD -SD Avg

P = 0.1923 ANOVA

Onset To Arrival in Colorado* (N = 1803)

*For pts arriving within 24 hours of symptom onset. (O-A unknown or >24 hours in 36% of pts.)

Outcome: The Benchmark

50%

38%

16%

23%

17%

18%

17%

21%

r-tPA

Placebo

No Disability Mod Disability Severe Disability Death

NINDS Study (Barthel Index at 3 Months)

Adapted from NEJM: 1995, 333:1581-1588

No Disability, TPA>Placebo (P = 0.008)

Improve: 33% Rel. 12% Abs. NNT: 8

Limitations of Local Experience(Numbers and Power)

• NINDS TPA Study said:– No disability p/ stroke, w/o TPA = 38%– No disability p/ stroke, w TPA = 50%

• To have an 80% chance of confirming this result with 95% confidence (P <0.05), one would need at least 266 subjects in each group (532 patients, in all).

Ordered Outcomes

No Disability

Mod Disability

Severe Disability

Death

Barthel at 3 Months

Home

Rehab

SNF, LTAC

Death, Hospice

Discharge Status (Surrogate)

1

3

2

4

Rank

Ordered Outcomes

Good

(No Disability)

Not Good

(Disability or Death)

Barthel at 3 Months

Good

(Home)

Not Good

(Not Home)

Discharge Status (Surrogate)

1

2

Rank

Comparing Outcomes For Ischemic strokes with NIHSS >4

CSR Data (DC Destination)

35%

24%

65%

76%

IV_TPA (153)

No_tPA ( 332)

Good (DC-Home) Not _DC_Home

NNT = 8NNT = 9

NINDS (Barthel Index)

50%

38%

50%

62%

r-tPA

Placebo

Good (No Disability) Not Good

For CSR Data: P = 0.01 Chi Square

Quality Stroke Care: Not Just TPA• Thrombolytic Administered• Antithrombotic Rx by Day 2• Deep Vein Thrombosis Prophylaxis • Dysphagia Screening• Discharged on Lipid Lowering Rx• Discharged on Antithrombotics• Anticoagulation Therapy for Atrial

Fibrillation• Smoking Cessation Counseling• Assessed for Rehabilitation• Stroke Education

Consensus GWTG, JCAHO, CMS Joint Performance Measures 2008

Evaluating the LDL Quality Indicator

0

20

40

60

80

100

120

140

2006_06 (17)

2006_07 (117)

2006_08 (104)

2006_09 (97)

2006_10 (101)

2006_11 (116)

2006_12 (127)

2007_01 (160)

2007_02 (156)

2007_03 (213)

2007_04 (163)

2007_05 (188)

2007_06 (154)

2007_07 (172)

2007_08 (172)

2007_09 (130)

2007_10 (72)

Year_Month (#Complete Records with IS or TIA)

# M

eeti

ng

Cri

teri

a

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

% M

eeti

ng

Cri

teri

a o

r M

eeti

ng

QI

#MeetingCriteria %Meeting Criteria %Meeting Criteria & Meeting QI Linear (%Meeting Criteria & Meeting QI)

Date of Analysis 12/28/07

Overall: N = 2259 IS or TIA; 1267 (56%) met criteria; 990 (78% of these) were treated

Linear regression for % meeting QI: P-value = 0.03

• Blood pressure treatment in acute stroke• Stroke prevention in atrial fibrillation• Stroke prevention with statins• Antiplatelet agents and stroke prevention

Optional issues