Ischemic Stroke Prevention Burden of Disease - Stroke A Primary Care Problem - 5+ million Americans have had a stroke - 800,000/year (600K first stroke) No conflict of interest - 20% mortality per event - 18% unable to return to work Jeff.kohlwes - 4% total custodial care @ucsf.edu $80 Billion U.S. annually AHA, Jan 27, 2015 Heart and Stroke Statistical Update Jeff Kohlwes MD, MPH Stroke and Women Stroke Definitions • 2x more than breast Ca 1. Stroke – Abrupt onset of a non- convulsive/non-metabolic focal • 3 rd leading cause of death neurological deficit lasting more than 24 (vs 5 th in men) hours • Worse outcomes 2. Transient Ischemic Attacks (TIA) – Focal – More long-term care non-convulsive/non-metabolic neurological changes lasting less than 24 hours – National Stroke Association (2015 guideline) Harrison ’ s Textbook of Medicine
Stroke and Women- Unique risk factors Etiologies of Strokes Meta-analysis 78 studies- >10 million subjects • Any Stroke: – Preterm delivery (1.62 RRI), Stillbirth (1.86 RRI), oophorectomy (1.42 RRI), Gestational HTN (1.52 RRI) • Ischemic Stroke: – Gestational HTN- 1.80 RRI • Hemorrhagic Stroke: – Menopause >55yo (2.24 RRI), Gestational HTN (5.10 RRI) • Migraine with aura, OCPs/HRT • Smoking increase in women Take Home Message: Up to 66% of all strokes are potentially – Poorthuis et al. Female Specific Risk Factors for Stroke JAMA Neurol. Nov. 14, 2016 preventable Percent Decline in Age-Adjusted Mortality Rates Case #1- What is the most important for Stroke by Sex and Race: United States, 1972-94 reason for the 60% reduction in strokes since the early 1970’s? 0 White men A- Reduced smoking rates in adults -10 White women Percent decline -20 B- Anticoagulation for atrial fibrillation Black men -30 Black women -40 C- Better lipid management -50 -60 D- Lying statistics -70 1970 1974 1978 1982 1986 1990 1994 E- Hypertension control Year The decline in age-adjusted mortality for stroke in the total population is 59.0%.
Hypertension is the biggest stroke Case #1- What is the most important risk factor reason for the 60% reduction in strokes since the early 1970’s? A- Reduced smoking rates in adults B- Anticoagulation for atrial fibrillation C- Better lipid management D- Lying statistics E- Hypertension control American Heart Association, 2002 Heart and Stroke Statistical Update , 2001; Galarza et al, Hypertension, 1997; Gorelick, Arch Neurol, 1995; Gorelick, Neuroepidemiology, 1997; He, J Hypertens , 1999. Systolic BP is directly correlated to risk of stroke SHEP Study- and HTN Control Hypertension - 44+% prevalence -Only 30% controlled Wolf-Maier et al- JAMA May 23 2003 Hypertension bottom line: 4700 patients >65 randomized to either diuretic or placebo - Aggressive control to JNC (and Bobby Baron) - mean SBP 170 - Total mortality over 4.5 years of study decreased 13% guidelines SHEP Cooperative Research Group, JAMA , 1991.
A 72 year old woman with controlled hypertension A 72 year old woman with controlled hypertension presents with 3 hours of mild dysarthria and left presents with 3 hours of mild dysarthria and left hand weakness that has resolved completely while hand weakness that has resolved completely while in the ER. She already takes 81mg of aspirin daily. in the ER. She already takes 81mg of aspirin daily. Her EKG in normal sinus and vascular imaging is Her EKG in normal sinus and vascular imaging is negative. How do you treat her? negative. How do you treat her? A- Increase dose of aspirin to 325mg daily A- Increase dose of aspirin to 325mg daily B- Change her to aspirin/dipyridamole 25/200 bid B- Change her to aspirin/dipyridamole 25/200 bid C- Add clopidogrel 75 mg daily C- Add clopidogrel 75 mg daily D- Change to warfarin adjusted INR from 2-3 D- Change to warfarin adjusted INR from 2-3 Match Trial Secondary Prevention: Plavix + Aspirin or European Stroke Prevention Trial 2 Plavix + Placebo • Factorial design (n=6202 for two years) • N=7599 followed for 18 months • Secondary prevention- stroke specific outcomes • Outcomes: CVA, MI, hospitalization or death – Placebo vs. ASA vs. DPA vs. DPA+ASA – Dual Rx. 596/3793 (15.7%) • Strokes ORs NNT/year – Clopidogrel 636/3802 (16.7%)- no asa alone arm…. – RRR 6.4% (-4.6-16.3) Asa 0.79 76 – Significant increase in bleeding on dual therapy DP 0.81 84 • Conclusions: Dual Rx no better than clopidogrel alone DP-ASA 0.59 36 – And probably no better than aspirin – VA Neuro- change antiplatelet agent -NO change in mortality rates » Lancet Vol. 364 July, 2004 Diener H, et al. ESPS 2: J Neurol Sci 1996;143:1-13
Severity of Subsequent Stroke ASA/DP vs. Clopidogrel • ESPS II data shows: RCT, 20K patients, 2.5 years Clopidogrel 75 vs. ASA/DP 25/200 HR= 1.01 for recurrent stroke 9% ASA/DP vs. 8.8% Clopidogrel • Antiplatelet agents reduce rate, lengthen time NEJM 359;12. Sept 18, 2008 – But NOT severity of subsequent stroke » Neurology, Vol 53(4). Sept 11, 1999 Your previous patient’s 51 year old neighbor is very afraid of having a stroke after watching a friend recently become Bottom Line: Antiplatelet Agents debilitated by one. She heard that aspirin prevents strokes in women. Her 10 year CV Framingham risk score is 8%. How • Aspirin first line therapy do you advise her? Stroke/TIA on asa then: https://www.cvdriskchecksecure.com/framinghamriskscore.aspx • Change to DP+ASA or Clopidogrel for A- Start aspirin 325 mg daily ASA breakthrough (no dual therapy) B- Start aspirin 81mg daily • No advantage to coumadin Mohr, NEJM, 2001; 345 C- Start aspirin 81mg every other day D- Risk outweighs benefits E- Shared decision making
Your previous patient’s 51 year old neighbor is very afraid of Aspirin and Primary Prevention having a stroke after watching a friend recently become debilitated by one. She heard that aspirin prevents strokes in women. Her 10 year CV Framingham risk score is 8%. How Non-fatal MI do you advise her? - RR, 0.78 - Began at 5 years https://www.cvdriskchecksecure.com/framinghamriskscore.aspx - No dosing diff. A- Start aspirin 325 mg daily B- Start aspirin 81mg daily Non-fatal C- Start aspirin 81mg every other day CVA D- Risk outweighs benefits (can be argued) - RR, 0.95 [CI, 0.85 to E- Shared decision making 1.06] Reviews |21 June 2016 Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic » 19% RRR in women for stroke- single study Evidence Review for the U.S. Preventive » Ridker et al. WHS N Engl J Med.2005;352:1293-304. Services Task Force. Annals of IM. ASA for Primary CV Prevention- Stroke Primary Prevention-ASA Bottom Line Aspirin vs no aspirin • The USPSTF believes the answer is “yes” for adults 50 to Outcomes at Number of RRI (95% 59 years of age who have a ≥ 10% 10-year CV risk, are not Weighted event rates NNH (CI) 4 to 10 y trials ( n ) CI) at increased risk for bleeding, have a life expectancy of ≥ Aspirin No aspirin 10 years, and are willing to take low-dose aspirin for ≥ 10 years Major 59% (32 to 461 (300 to gastrointestin 7 (94 307) 0.59% 0.37% 90) 849) al bleeding • For other adults (most patients), the USPSTF recommends Hemorrhagic 33% (3 to 1599 (744 to 9 (113 266) 0.25% 0.19% individual decision-making. stroke 71) 17 579) Whitlock EP, Burda BU, Williams SB, Guirguis-Blake JM, Evans CV. Bleeding risks with aspirin use for primary prevention in adults: a systematic review for the U.S. Preventive Services Task Force . Ann Intern Med. 2016; 164:236-45.
Case 3- Which of the following statements about Case 3- Which of the following statements about stroke prevention in atrial fibrillation is false? stroke prevention in atrial fibrillation is false? A- Strokes due to afib are more common with A- Strokes due to afib are more common with increasing age. increasing age. B- Coumadin reduces mortality in atrial fibrillation B- Coumadin reduces mortality in atrial fibrillation C- Aspirin reduces stroke in atrial fibrillation C- Aspirin reduces stroke in atrial fibrillation D- Cardioversion prevents stroke in atrial D- Cardioversion prevents stroke in atrial fibrillation fibrillation E- Hypertension control remains the most E- Hypertension control remains the most important preventable stroke risk factor important preventable stroke risk factor Rate vs Rhythm Control on Stroke Atrial fibrillation follow-up investigation of rhythm management- AFFIRM Randomized 4060 patients to cardioversion vs rate control All received coumadin - Common disorder, increases with age - Stroke risk increases: - Rate control=rhythm control - 17X for valvular afib - -paroxysmal afib=chronic afib - 5 times for nonvalvular - -high rates of stroke after d/c of coumadin - How to RX? Circulation 201: 103:162-182
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