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