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

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.

100% 80% 65% 78% 60% 48% 40% 20% 6% 16% 31% 0% 18-34 35-44 45-54 55-64 65-74 75+ *Based on NHANES 1999 2000 data. Hypertension is defined as blood pressure 140/90 mmhg or antihypertensive treatment. Fields et al. Hypertension. 2004:44;398-404.

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

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 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 Dose No. of Trials OR (%) 500-1500 mg 34 19 160-325 mg 19 26 75-150 mg 12 32 <75 mg 3 13 Any aspirin 65 23 0 0.5 1.0 1.5 2.0 Antiplatelet Better *Vascular events included nonfatal MI, nonfatal stroke, and death from vascular causes. Treatment effect P<.0001. Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86. Odds Ratio Antiplatelet Worse

Aspirin within 24hrs after CVA 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.

Clopidogrel 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

CAPRIE: Clopidogrel Cumulative Event Rate (Myocardial Infarction, Ischemic Stroke or Vascular Death) Cumulative event rate (%) 16 12 8 4 ASA (n=9,586) 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months of follow-up Clopidogrel (n=9,599) 8.7% * Overall relative Risk Reduction p=0.043 *Intention to treat analysis 1. CAPRIE Steering Committee. Lancet 1996; 348: 1329 1339. 2. Antiplatelet Trialists' Collaboration. BMJ 2002; 324: 71 86.

CAPRIE: Clopidogrel Results: Overall safety = asa. Sl. more effective in reducing end- points (cva/mi/vasc.d) all pt result driven by subset of PVD pts CAPRIE

CHARISMA MATCH Bhatt D et al. N Engl J Med 2006;354:1706-1717 Diener et al. Lancet 2004;364:331-337

Dipyridamole 30 325mg Aspirin and 200 Dipyridamole BID versus 30-325mg Aspirin Alone (ESPRIT) n=2739 all with stroke or TIA Dipyridamole stopped 470 ASA alone stopped 184 1% event reduction per year ESPRIT Study Group. Lancet 2006;367:1665-1673.

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:

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

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. Anti inflammatory properties Anti thrombotic 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% (NNT 15 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.

NEJM 2009 p=0.34 p<0.001

NEJM 2009

Schloten et al. Europace 2005

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 The ACTIVE Investigators. N Engl J Med 2009;10.1056/NEJMoa0901301

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

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

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

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

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

Antithrombotics+high dose statins +Diet&exercise+Tight BP control Hackam, D. G. et al. Stroke 2007;38:1881-1885

Percentage of respondents unable to name correctly 1 warning sign or risk factor. Pancioli, A. M. et al. JAMA 1998;279:1288-1292 Copyright restrictions may apply.

Stroke 2011 Stroke 2011