Branko N Huisa M.D. Assistant Professor of Neurology UNM Stroke Center.
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Stroke Prevention Update
Branko N Huisa M.D.Assistant Professor of NeurologyUNM Stroke Center
THE END!
CHANGABLE
• Blood pressure
• Diabetes Mellitus
• Hyperlipidemia
• Atrial fibrillation
• Nicotine
• Drug abuse
• Life style
NOT CHANGABLE• Age
• Sex
• Race
• History of TIA or stroke
• Family history of TIA/stroke
Prevention – risk factors
Stroke Prevention Treatments
Antihypertensive medication.Diabetic control.Tobacco cessation.Antiplatelets.Anticoagulants.Statins.Diet.Exercise.Education.
Prevalence of hypertension in USA*
6%
16%
31%
48%
65%
78%
0%
20%
40%
60%
80%
100%
18-34 35-44 45-54 55-64 65-74 75+*Based on NHANES 19992000 data. Hypertension is defined as blood pressure 140/90 mmHg or antihypertensive treatment.Fields et al. Hypertension. 2004:44;398-404.
Adults who had been told they have high BP. CDC 2007
People who were ever told they had a stroke. CDC 2008
Relative risks of stroke and CHD, estimated from combined results.
Lancet 1990
BP reduction
s between groups
with risks of
major vascular
outcomes and death
Lancet 2003SBP difference between randomized groups (mm Hg)
Stroke risk in 61 prospective trials, >12.7 million patient years
Lancet 2002; 360: 1903–13.
Stroke risk in 61 prospective trials, >12.7 million patient years
Reduce 10mmHg diastolic BPReduce 20mmHg systolic BP
Lancet 2002; 360: 1903–13.
Blood pressure and stroke NNT
No severe hypertension. NNT=118 (DBP 90-110 mm Hg).
Moderate hypertension. NNT =52 (DBP at or below 115 mm Hg)
Severe hypertension. NNT=29 (DBP above 115 mm Hg)
Secondary prevention: NNT=110 (for patients with initial BP <160/90
mmHg and reduction by 12/5 mm Hg) PROGRESS Lancet 2001
Aspirin Mechanism: (inhibits PG synthesis)
Inhibits PGH synthase pre- systemically.
Covalently acetylates Cyclo-oxygenase (irr.)
Inhibits platelet function by 1 hour. Lasts entire platelet lifetime (~10d) Efficacy is not in question. Controversy:
o Dosageo Aspirin resistance
Aspirin
0 0.5
1.0
1.5 2.0
500-1500 mg 34 19160-325 mg 19 2675-150 mg 12 32<75 mg 3 13
Any aspirin 65 23
Antiplatelet Better
Antiplatelet Worse
Aspirin Dose No. of Trials OR (%)
Odds Ratio
Efficacy of Aspirin at Various Doses in Reducing Vascular Events* in High-Risk Patients
*Vascular events included nonfatal MI, nonfatal stroke, and death from vascular causes.Treatment effect P<.0001.Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86.
CAST & IST:Metaanalysis ~40,000 pts.• ~99% of evidence from
randomized trials.• Reduction of 9/1000
overall risk of further cva/ death in hospital.
• Reduction of 7/1000 ischemic cva. (p<0.000001)
* Starting ASA early reduces risk of recurrent cva.
______________Chen. Stroke 2000;31:1240.
Aspirin within 24hrs after CVA
CAPRIE: (Clopidogrel vs ASA)• Clopidogrel(75mg)
ASA(325mg)• 19,185 pts. c h/o CVA/ MI/ PVD • Incidence 5.83% (ASA)
5.32%
(Clopidogrel)
* 8.7% (p=0.05) Relative RR.______________CAPRIE
Clopidogrel
Cumulative Event Rate (Myocardial Infarction, Ischemic Stroke or Vascular Death)
Months of follow-up
8.7%*
Overallrelative
RiskReduction
0
4
8
12
16
0 3 6 9 12 15 18 21 24 27 30 33 36
Cum
ulat
ive
even
t rat
e (%
)
p=0.043Clopidogrel(n=9,599)
1. CAPRIE Steering Committee. Lancet 1996; 348: 1329–1339. 2. Antiplatelet Trialists' Collaboration. BMJ 2002; 324: 71–86.
*Intention to treat analysis
ASA(n=9,586)
CAPRIE: Clopidogrel
______________CAPRIE
• Overall safety = asa.
• Sl. more effective in reducing end- points (cva/mi/vasc.d)
• “all pt” result driven by subset of PVD pts
Results:
CAPRIE: Clopidogrel
Bhatt D et al. N Engl J Med 2006;354:1706-1717
Diener et al. Lancet 2004;364:331-337
ASA and Clopidogrel vs. ASA
CHARISMA MATCH
ESPRIT Study Group. Lancet 2006;367:1665-1673.
30–325mg Aspirin and 200 Dipyridamole BID versus 30-
325mg Aspirin Alone (ESPRIT)
Dipyridamole
n=2739 all with stroke or TIADipyridamole stopped 470ASA alone stopped 1841% event reduction per year
ESPRIT:Conceptual Design Limitations
• ESPRIT is an un-blinded trial• Patients and physicians were aware of
applied medication with potential bias• 400 mg daily dipyridamole with different
formulations • extended (modified) release • immediate release
• Aspirin dose from 30 to 325 mg
De Schryver et al. Cerebrovasc Dis. 2000;10:147-50.
PROFESS:
Antiplatelets conclusion:Which one is better:
“There is no evidence to conclude superiority of one antiplatelet therapy over other.”
“Antiplatelet therapy should be used for secondary stroke prevention. NNT ≈ 100”
AHA Guidelines Stroke 2011
Effects of Intensive Glucose Lowering in Type 2 Diabetes
ACCORD NEJM 2008
ACCORD NEJM 2008
Diabetes and stroke prevention Tight Glucose
controlMaybe
Tight BP control YES!
UKPDS. BMJ 1998
The magic pill: STATINS
Effect of Statins
Lower LDL cholesterol.Modest increase of HDL cholesterol. Improve endothelial dysfunction. Increase NO.Neuroprotective effect.Anti‐inflammatory propertiesAnti‐thrombotic effects Immunomodulation
Atovastatin for secondary stroke prevention: SPARCL
NEJM 2006
Huisa et al 2010
Atorvastatin for the Secondary Stroke Prevention: SPARCL
Atorvastatin and NNT
Based on SPARCL: NNT=46 in 5 years
High dose therapy with a reduction of LDL>50% (NNT≈15 in 5 years)
Atrial Fibrillation and Stroke
Atrial fibrillation and Stroke (Meta Analysis
16 trials on stroke prevention in AF (n=9874)
Warfarin reduced stroke by 62% absolute reduction 2.7% for primary and
8.4% for secondary preventionAspirin reduced stroke by 22%
absolute 1.5 and 2.5%
Hart RG, et al. Stroke 1999.
Coumadin and NNT
RE-LY
p=0.34
p<0.001
NEJM 2009
RE-LY
NEJM 2009
Stroke prevention after A-fib
Risk factors in addition to afib
Schloten et al. Europace 2005
The ACTIVE Investigators. N Engl J Med 2009;10.1056/NEJMoa0901301
Patients who have AF but cannot take warfarin
n=7,554
3.6 years
All received ASA
Major vascular events: clopidogrel 6.8% / year, placebo 7.6% / year)
Stroke: clopidogrel 2.4% per year, placebo 3.3% per year
Major bleeding: clopidogrel 2.0% per year, placebo 1.3% per year
AVERROES
Cumulative Hazard Rates for the Primary Efficacy and SafetyOutcomes,According to Treatment Group
N Engl J Med 2011
DIET AND STROKE
DIET
MediterraneanLow carbohydrateLow Fat
EAT LESS LIVE LONGER!
DIRECT Study NEJM 2008
N :322, BMI:31
DIRECT Study NEJM 2008
Dietary Intervention to Reverse Carotid Atherosclerosis
Shai et al. Circulation 2010
Fast Food Neighborhood and Stroke Risk
Morgestein et al. Ann Neurol 2009
RR(95% CI): 1.13 (1.02–1.25)
Diet and Salt
Adult human body requirements:< 5.8 g of salt mg (AHA 2010)
Ideal for stroke prevention< 4 g of salt
Average USA consumption10.4 g of salt per mg(CDC 2006)
Projected Annual Reductions in Cardiovascular Events Given a Dietary Salt Reduction of 3 g per Day. NEJM2010
Projected Estimates of Comparative Effect of Various Population Interventions on Annual Reductions in Cardiovascular Events
NEJM2010
How to reduce dietary sodium Eat more fresh foods, especially fruits and
vegetables Purchase processed foods with low salt
claims on labels, or brands with the lowest % of daily sodium intake on the food label.
Avoid heavily salted foods (pickled foods, olives, salted crackers or snacks, process meats, etc).
Rinse canned foods with water before eating
Use less salt in home cooking and no added salt at the table.
Good things on your diet that might reduce your risk…
How to prevent stroke
Antihypertensive medication.
Diet.Statins.Antiplatelets. Exercise and body weight. Tobacco cessation. Diabetic control.
Anticoagulants for A-fib
Hackam, D. G. et al. Stroke 2007;38:1881-1885
Antithrombotics+high dose statins+Diet&exercise+Tight BP control
Patient Education
Percentage of respondents unable to name correctly 1 warning sign or
risk factor.
Pancioli, A. M. et al. JAMA 1998;279:1288-1292
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Stroke 2011
Stroke 2011
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