anti platlet and stroke

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Anti-platelet and Stroke

Surat Tanprawate, MD, MSc(Lond.), FRCP(T)Division of Neurology, Chiang Mai University

12.9.2011CMCC, Chaing Mai, Thailand

Wednesday, September 14, 2011



TOAST subtype of acuteischemic stroke

• 1) large-arteryatherosclerosis

• 2) cardioembolism

• 3) small-vesselocclusion

• 4) stroke of otherdetermined etiology

• 5) stroke of undetermined etiology

Stroke. 1993 Jan;24(1):35-41.




1989

Ticlopidine-TASS: NEJM- CATS: Lancet

Aspirin-CAST: Lancet

-IST: Lancet

19971996

Clopidogrel-CAPRIES

2000

ASA/ Dipyridamol-ESPS-2

2002

Antithrombotic

TrialistCollaboration:BMJ

2003 2006

Triflusal-TACIP study

ASA/Dipyridamol vsClopidogrel-PRoFESS study

ASA vs ASA/

Clopidogrel-MATCH study

Cilostazol-CSPS

2008 2011

ESO

stroke

guideline

ASA/

AHAstroke

guideline

ASA/Dipyridamol

vs ASA-ESPRIT study

1978

Aspirin-Canadian

CooperationStudyGroup: NEJM




Aspirin

Large scale trials &Meta-analysis

• Acute ischemic stroke: 300mg of ASA can reduce RR of

recurrent ischemic strokeby 24-28%

• Long tern prevention:30-1500 mg of ASA canreduce RR of subsequentvascular events (includingstroke) by 13-18%

IST trial. Lancet 1997;349:1569–1581

CAST Collaboration Group. Lancet 1997;349:1641–1649

Algra et al. J Neurol Neurosurg Psychiatry 1996;60:197–199




Hemorrhagic strokerisk

• 16 trials, 66542 patients

• 108 hemorrhagic strokes

• Risk 0.05% per year

GI bleeding

• Meta-analysis 24 RCTs with 66,000patients

• 0.45% annual bleeding rate

• OR 1.68 (95% CI 1.51-1.88)




Clopidogrel

CAPRIE(Clopidogrel versus Aspirin in

Patients at Risk of Ischemic Events)

“1996”

ASA/DipyridamoleESPS-2(European Stroke Prevention Study-2)




CAPRIE study

• N=19185

• History of ischemic stroke, MI, orperipheral vascular disease

• Clopidogrel 75mg vs aspirin 325mg



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CAPRIE Study: Efficacy*

† 2-year study, N = 19,185, endpoint incidence calculated per year.

‡ P < 0.05

Endpoint†

Stroke

Stroke, MI, or

vascular death

RRR

Stroke

Patients

8.0%

7.3%

MI

Patients

–1.0%

–3.7%

PAD

Patients

1.2%

23.8%‡

Total

6.1%

8.7%‡

CAPRIE Steering Committee. Lancet . 1996;348:1329.

* Clopidogrel (75 mg qd) vs ASA (325 mg qd).




ASA+dipyridamole

A D

Tested efficacy of ASA/ER-DP for secondary stroke preventionN=6602 (ASA 50 mg/d, Dipyridamole 400 mg/d)




ESPS 2: Effects on Stroke—Relative

Risk Reduction(Pairwise Comparisons)

ER-DP = Extended-Release Dipyridamole

ASA = Acetylsalicylic Acid

RRR = Relative Risk Reduction

ESPS 2 Group.J Neurol Sci.

1997; 151(suppl):S1-S77.

37.0%P < 0.001

16.3%P = 0.039 18.1%

P = 0.013 23.1%

P = 0.006

0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% 40.0%

RRR

ASA/ER-DP vs. Placebo

ER-DP vs. Placebo

ASA vs. Placebo ASA/ER-DP vs. ASA




ESPS 2: Adverse Events(Percent within each group)

ER-DP = Extended-Release Dipyridamole

ASA = Acetylsalicylic Acid

Treatment group Dyspepsia GI Bleeding Headache

ASA/ER-DP

Placebo

ASA

ER-DP

18.4

16.7

18.1

17.4

4.1

2.1

3.2

2.2

39.2

32.9

33.8

38.3

*Not statistically different from aspirin

*

19

Aggrenox®

(aspirin/extended-release dipyridamole) 25 mg/200 mg capsules product information, Boehringer Ingelheim Pharmaceuticals, Inc.




Clopidogrel

CAPRIE(Clopidogrel versus Aspirin in

Patients at Risk of Ischemic Events)

“1996”

ASA/DipyridamoleESPS-2(European Stroke Prevention Study-2)




Clopidogrel +

ASAvs Clopidogrel

2004

ASA 75 mg + Clopidogrel 75 mg

7599 patients with ischemic stroke

or TIA




16.7 15.7

0

5

10

15

20

%

C C+A

Stroke, MI, Vascular Death,

Rehospitalization

Primary Endpoint

RRR = 6.4% p=.244

1.3

2.6

0.6

1.9

0

0.5

1

1.5

2

2.5

3

%

Life-threatening Major

Hemorrhage Rates

C

C+A

A non-significantdifference in reducingmajor vascular events.

The risk of life-threatening or majorbleeding is increasedby the addition of

aspirin.




Trifusal vs Aspirin...

TACIP study Stroke 2003

N=2113TIA or non-disablingstroke




12.4% 13.1%

0

10

20

P= 0.65

130 138

ASPIRINN= 1.052

TriflusalN= 1.055

Incidence

days

Survival analysis

S u r v i v a l F u n c t i o n

1.0

0.9

0.8

0.7

0.6

Log-Rank; p = 0.5

0 100 200 300 400 500 600 700 800 900 1000 1100

ASPIRIN

TRIFLUSAL

CLINICAL TRIALS

Stroke 2003; 34: 840-848

TACIP Study

Results: PRIMARY ENDPOINTCombined incidence of non-fatal ischemic stroke, non-fatal AMI,

cardiovascular death

3 years




*Include: systemic and cerebral haemorrhage, fatal and non-fatal

Results: Patients with hemorrhagic adverse events

ANY MINOR

ANY MAJOR*

ANY MAJOR OR MINOR

Gastro-intestinal

Skin haematoma

Respiratory

Urinary

Cerebral

Ocular

22.1%

4.0%

25.2%

8.5%

7.8%

7.0%2.3%1.0%

1.0%

<0.001

0.004

<0.001

0.01

0.001

n.s.n.s.n.s.n.s.

15.2%

1.9%

16.7%

5.6%

4.5%

5,3%1,9%0.7%

0.6%

ASPIRINN= 1.052

TRIFLUSALN= 1.055

P value

CLINICAL TRIALS

Stroke 2003; 34: 840-848

TACIP Study




TACIP Study

Triflusal vs Aspirin

• This study showed a similar

efficacy of triflusal and aspirin inthe long term prevention of

vascular events after stroke.

• Triflusal was associated with a

significantly lower rate of

hemorrhagic complications.

Stroke 2003; 34: 840-848




Other clinical trials

• CSPS

• Cilostazol = ASA

• Less hemorrhagic risk

• PRoFESS study

• ASA/Dipyridamole vs Clopidogrel

• Similar rate of recurrent stroke between

two groups




Thank You

for

Your Kind

Attention

My Deep Gratitude to... Asso.Prof. Siwaporn Chankrachang

Dr. Kanokwan Watcharasaksin

Dr. Nantaporn Teeyapan

and my colleagues

anti platlet and stroke

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