Branko N Huisa M.D. Assistant Professor of Neurology UNM 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

Antihypertensive medication. Diabetic control. Tobacco cessation. Antiplatelets. Anticoagulants. Statins. Diet. Exercise. Education.

*Based on NHANES data. Hypertension is defined as blood pressure 140/90 mmHg or antihypertensive treatment. Fields et al. Hypertension. 2004:44;

Lancet 1990

BP reductions between groups with risks of major vascular outcomes and death Lancet 2003 SBP difference between randomized groups (mm Hg)

Lancet 2002; 360: 1903–13.

Reduce 10mmHg diastolic BP Reduce 20mmHg systolic BP Lancet 2002; 360: 1903–13.

No severe hypertension. NNT=118 (DBP 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 Dosage o Aspirin resistance Aspirin

mg mg mg <75 mg 3 13 Any aspirin Antiplatelet BetterAntiplatelet Worse Aspirin Dose No. of Trials OR (%) Odds Ratio *Vascular events included nonfatal MI, nonfatal stroke, and death from vascular causes. Treatment effect P< 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< ) * 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 Incidence5.83% (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% * Overall relative Risk Reduction Cumulative event rate (%) p=0.043 Clopidogrel (n=9,599) 1. CAPRIE Steering Committee. Lancet 1996; 348: 1329– 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: Diener et al. Lancet 2004;364: CHARISMAMATCH

ESPRIT Study Group. Lancet 2006;367: –325mg Aspirin and 200 Dipyridamole BID versus mg Aspirin Alone (ESPRIT) Dipyridamole n=2739 all with stroke or TIA Dipyridamole stopped 470 ASA alone stopped 184 1% event reduction per year

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:

PROFESS:

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

ACCORD NEJM 2008

Tight Glucose control Maybe Tight BP control YES! UKPDS. BMJ 1998

Lower LDL cholesterol. Modest increase of HDL cholesterol. Improve endothelial dysfunction. Increase NO. Neuroprotective effect. Antiinflammatory properties Antithrombotic effects Immunomodulation

NEJM 2006

Huisa et al 2010

Based on SPARCL: NNT=46 in 5 years High dose therapy with a reduction of LDL>50% (NNT15 in 5 years)

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 prevention Aspirin reduced stroke by 22% absolute 1.5 and 2.5% Hart RG, et al. Stroke 1999.

p=0.34 p<0.001 NEJM 2009

Schloten et al. Europace 2005

The ACTIVE Investigators. N Engl J Med 2009; /NEJMoa Patients who have AF but cannot take warfarin n=7, 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

Cumulative Hazard Rates for the Primary Efficacy and Safety Outcomes,According to Treatment Group N Engl J Med 2011

Mediterranean Low carbohydrate Low Fat EAT LESS LIVE LONGER!

N :322, BMI:31

Dietary Intervention to Reverse Carotid Atherosclerosis Shai et al. Circulation 2010

Morgestein et al. Ann Neurol 2009 RR(95% CI): 1.13 (1.02–1.25)

Adult human body requirements: < 5.8 g of salt mg (AHA 2010) Ideal for stroke prevention < 4 g of salt Average USA consumption 10.4 g of salt per mg (CDC 2006)

Projected Annual Reductions in Cardiovascular Events Given a Dietary Salt Reduction of 3 g per Day. NEJM2010

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.

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: Antithrombotics+high dose statins +Diet&exercise+Tight BP control

Percentage of respondents unable to name correctly 1 warning sign or risk factor. Pancioli, A. M. et al. JAMA 1998;279: Copyright restrictions may apply.

Stroke 2011