ANTIPLATELET THERAPY FOR STROKE PREVENTION LESSONS LEARNED FROM SPS3 Oscar R. Benavente, MD, FRCPC Professor & Research Director of Cerebrovascular Health and Stroke Division of Neurology Vancouver Stroke Program - UBC Vancouver. December 1, 2012 14 TH WESTERN STROKE CONFERENCE
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Antiplatelet Therapy for Stroke Prevention Lessons Learned from SPS3
14 th Western Stroke Conference. Antiplatelet Therapy for Stroke Prevention Lessons Learned from SPS3. Oscar R. Benavente, MD, FRCPC Professor & Research Director of Cerebrovascular Health and Stroke Division of Neurology Vancouver Stroke Program - UBC. Vancouver. December 1, 2012. - PowerPoint PPT Presentation
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ANTIPLATELET THERAPY FOR STROKE PREVENTION LESSONS LEARNED
FROM SPS3
Oscar R. Benavente, MD, FRCPCProfessor & Research Director of Cerebrovascular Health and Stroke
Division of Neurology
Vancouver Stroke Program - UBC
Vancouver. December 1, 2012
14TH WESTERN STROKE CONFERENCE
2
Stroke Facts Stroke Facts
15 million stroke / year
6 million deaths 5 million disable
Projected 8 million deaths by 2030
More than 60% deaths in <70 yrs of age
Reduction of 4%/yr = 6 million fewer deaths in the
next 10 yrs
stroke
MI or CHD
stroke, MI or VD
RISK OF RECURRENT STROKE, AND OTHER VASCULAR EVENTS AFTER
TIA AND STROKE
Pendlebury et al. Cerebrovascular Dis 2009
5
Atherothrombosis Is a Polyvascular Disorder: Overlap Between PAD, CAD, and
CVD
Atherothrombosis Is a Polyvascular Disorder: Overlap Between PAD, CAD, and
CVD
Bhatt DL et al. JAMA. 2006;295:180-189.
Patients with one manifestation often have coexistent disease in other vascular beds
PAD
4.7%
1.2%
4.7%
1.6%
CVD
CAD
N=7013
44.6%
16.6%
8.4%
Number of Patients
6602 ESPS-2 1
6431a CAPRIE 2
2435 UK-TIA 3
2500 ESPS-1 4
3069 TASS 5
1072 CATS 6
Stroke Patients With CAD (%)b
0 10 20 30 40
Prevalence of Coronary Artery Disease
in Stroke Patients
a CAPRIE data represent only the
stroke subset of patients.b CAD history includes MI, angina, unstable angina, ischemic heart disease.
Aspirin reduces vascular events (including stroke) about equally in patients with vascular disease, including:- Young and old- Men and women- Hypertensives and non-hypertensives- Diabetics and non-diabetics
CHARISMA: Primary Efficacy Results (MI/Stroke/CV Death)* by
Inclusion Criteria
0.6 0.8 1.41.2Clopidogrel betterPlacebo better
1.60.4
*First occurrence of MI (fatal or nonfatal), stroke (fatal or nonfatal), or CV death.Bhatt DL. Presented at: American College of Cardiology Annual Scientific Session; March 11-14, 2006, Atlanta, GA.Bhatt DL et al. N Engl J Med. 2006;354:1706-1717.
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10
8
6
4
2
0
Months since randomization
Pri
ma
ry o
utc
om
e e
ve
nt
rate
(%
)
RRR: 17.1 [95% Cl: 4.4%, 28.1%]
p=0.01
8.8%
7.3%
N=9,478
Placebo + ASA
Clopidogrel + ASA
0 6 12 18 24 30
Bhatt et al. JACC vol 49, No 19, 2007Cardiovascular Death, MI or Stroke
Prior Myocardial Infarction, Stroke or Peripheral Artery Disease
“CAPRIE-like cohort” Analysis from CHARISMA
14 events are prevented treating 1000 pts for 27 months at a cost of 14 events are prevented treating 1000 pts for 27 months at a cost of 2 severe bleeds2 severe bleeds
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Prior MI
Prior IS
Prior PAD
Entire Cohort
0.5 1 2
Placebo Clopidogrel HR (95% & Cl) p-Value
8.3% 6.6% 0.774 (0.613, 0.978)0.031
10.7% 8.4% 0.780 (0.624, 0.976)0.029
8.7% 7.6% 0.869 (0.671, 1.125)0.285
8.8% 7.3% 0.829 (0.719, 0.956)0.010
Bhatt et al. JACC vol 49, No 19, 2007
3846
2838
3245
Prior Myocardial Infarction, Stroke or Peripheral Artery Disease
“CAPRIE-like cohort” Analysis from CHARISMA
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Rates of Vascular Death, MI or Stroke at Different Time Intervals from Event to
CHARISMA Trial: effect of clopidogrel + ASA early after TIA/Stroke
International Journal of Stroke, Feb 2011, 3
PROFESS Stroke Recurrence
Note: Slides reproduced accurately based on data orally presented. Not validated with a published source. This data curve have been redrawn.R Sacco. Presented at ESCo 2008.
PROFESS Characterization of First Recurrent Stroke
Note: Slides reproduced accurately based on data orally presented. Not validated with a published source.R Sacco. Presented at ESCo 2008.
Terutroban vs aspirin in patients with stroke/TIA: PERFORM trial
19,000 patients in 802 centers in 46 countriesMean follow up 2.3 yrs
Primary endpoint: composite stroke, mi, vascular death
Terurobran: 11%
Aspirin: 11%
Bousser, MG. Lancet 2011;337:2013-22
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Anticoagulant vs. Aspirin after Non-cardioembolic Brain Ischemia
The Major Randomized Trials
n achieved
INR
aspirin dosage
findings
SPIRIT (1997)
1316
3.3 30mg AC not safe;3.7%/yr ICH
WARSS (2001)
2206
1.9 325mg About equal
WASID (2005)
569 2.4 1300mg ended 05
ESPRIT (2007)
1064 2.6 30-325mg
ended 06
Stroke subtype and response to antithrombotic agents
SPS3 is sponsored by National Institutes of HealthSPS3 is sponsored by National Institutes of HealthNINDS: 2 U01 NS38529-04A1NINDS: 2 U01 NS38529-04A1
n= 283
n= 1677
n= 165
n= 171
n= 186
n= 127
n= 45
n= 366
81 clinical sites8 countriesRandomization: March 2003 - April 2011
SPS3
SPS3 Design I• Randomized multicenter international trial.• Investigator initiated study.• Lacunar strokes within 180 days, verified by MRI.• No cortical stroke, cardioembolic disease / carotid stenosis.• Randomized to 2 interventions in a factorial design: