Secondary Stroke Prevention Acute stroke conference, Sunnybrook Estates January 20, 2011 Rick Swartz HBSc, MD, PhD, FRCPC Assistant Professor, Department of Medicine, Divisions of Neurology and Obstetrical Medicine, Director, University of Toronto Stroke Program Sunnybrook Health Sciences Centre, University of Toronto R.H.Swartz, University of Toronto.
Disclosures Salary support: Heart and Stroke Foundation Centre for Stroke Recovery CIHR/CSN Focus on Stroke Advisory Boards: None. Speaker s Honararia: GTA stroke conference, Ontario Stroke Day. Bristol-Myers Squibb Canada Trials: None. No stock in pharmaceutical companies rick.swartz@sunnybrook.ca R.H.Swartz, University of Toronto.
Objectives To review basic epidemiology of stroke and rationale for stroke prevention efforts To review secondary prevention strategies and outline an approach to the art & science of secondary prevention R.H.Swartz, University of Toronto.
Stroke is a brain attack sudden loss of specific brain functions from damage to one part of the brain secondary to: an interruption of that region s blood supply (ischemic ~ 85%) OR bleeding into that area of brain (hemorrhagic ~15%) R.H.Swartz, University of Toronto
http://www.strokecenter.org/ R.H.Swartz, University of Toronto
Basic epidemiology of stroke 1 stroke every 10 minutes in Canada #1 leading cause of adult disability in Canada 2 nd leading cause of death worldwide Overall, ~20% fatal; 60-75% some disability ~50,000 Canadians annually have strokes resulting in death or serious disability. http://www.canadianstrokenetwork.ca/ World Stroke Day Proclamation, Stroke 2008;39 R.H.Swartz, University of Toronto
Outcome of Stroke Adapted from Hacke 1998, Asplund, 1997 About 50% are either dead or disabled Prognosis of hemorrhage is worse Adapted from Stegmayr B, et al. Stroke 1997;28:1367-1374
Stroke outcome in round numbers For every 10 stroke patients 2 will die 2 will recover 6 will be left with disability ICES data, 2001 Dr. David Gladstone, 2004
Basic epidemiology of stroke ~300,000 Canadian survivors live at risk for: another stroke (20% in 2 years) post-stroke dementia & post-stroke depression. < 50% survivors return to work lost income. 50% caregivers develop emotional illness within 1 year (care for the caregivers). Estimated direct and indirect costs of stroke are ~$4 BILLION annually in Canada. http://www.canadianstrokenetwork.ca/ R.H.Swartz, University of Toronto
So Strokes are common (and silent strokes = 3x symptomatic!) Strokes kill and disable people. Fortunately, some of this burden is also preventable Stroke is common, serious and treatable we can make a difference R.H.Swartz, University of Toronto
A brief interlude for motivation We will cure more people by aggressively managing risk factors than we will EVER cure with tpa. R.H.Swartz, University of Toronto
http://www.strokebestpractices.ca/
Primary Prevention of Stroke Primary prevention means treating us modifying risk factors before symptoms or illnesses occur (individuals & populations) We treat far more people for primary prevention, and the event you re trying to prevent is rarer. Thus, treatments have to be VERY safe and effective in populations. R.H.Swartz, University of Toronto
Primary Prevention of Stroke (& heart disease) Blood pressure lowering Atrial fibrillation (CHADS 2 ) Smoking cessation Diabetes treatment Cholesterol treatment Weight loss / abdominal obesity / exercise Low-risk drinking guidelines http://www.preventstroke.ca Stroke. 2006;37:577-617 R.H.Swartz, University of Toronto
Secondary Stroke Prevention Treatment of those with prior stroke or TIA, regardless of etiology 1) Why treat? 2) When to treat? 3) Who to treat? 4) What to treat? R.H.Swartz, University of Toronto
Secondary Prevention 1) Why treat? In people with TIAs discharged from ER: 12% are readmitted to hospital within 30 days 9 12% recurrent stroke or death within 30 days! 9% for TIA with speech deficit 12% for TIA with motor deficit Also need to treat FAST Gladstone et al. CMAJ 2004 R.H.Swartz, University of Toronto
Secondary Prevention 2) when? Stroke After TIA Canadian Data (slide courtesy Dr. F. Silver) 9.5 % 14.5 % 21.8 %
When treat? Early Risk of Stroke After TIA Gladstone et al. CMAJ 2004 Half of the strokes occurred in the first 2 days (slide courtesy Dr. D. Gladstone)
2) When to treat? 23% of patients with ischemic stroke have had a TIA before their stroke 17% occur the day of the stroke, 9% the previous day, 43% had a TIA during the 7 days prior to the stroke. pooled analysis from population and RCT s (OXVASC, OCSP, UK-TIA and ECST). Rothwell & Warlow, Neurology, 2005;64:817-20. R.H.Swartz, University of Toronto
2) When to treat? EXPRESS Study Rothwell et al. Lancet 2007 Phase 1 vs. 2 90-day stroke risk from 10% to 2% Medications started right away Carotid endarterectomy expedited R.H.Swartz, University of Toronto
2) When to treat? Urgent assessments prevent stroke FASTER Kennedy et al. Lancet Neurology 2007 Fast Assessment of Stroke and TIA to prevent Early Recurrence ASA +/- clopidogrel +/- simvastatin in 24 hours Stroke risk: 10.8% vs. 7.1% in favour of ASA/clopidogrel combination (n.s.) SOS-TIA Lavallee et al. Lancet Neurol 2007 24 hours TIA unit had lower event rates than expected from ABCD 2 score (1.24% vs. 5.96%)
Secondary Prevention 3)Who to treat? Risk Stratification with ABCD2 vs. Motor or speech TIA s Age 1 point if >60 years Blood pressure 1 point if sbp >140 or dbp >90 Clinical features 2 points for unilateral weakness; 1 point speech deficit without weakness Duration 2 points if >60 min; 1 point if >10-59 min Diabetes 1 point 2-day stroke risk: 1% (0-3 points), 4% (4-5 points), 8% (6-7 points) 90-day stroke risk up to 25% Johnston, Rothwell, et al. Lancet 2007; 369:283-92
Who to treat? The problem with ABCD s It isn t always as simple as the ABC s For example: 61 y.o. woman with mild HTN and diet controlled DM, who had >2 hours of dizziness 58 y.o. man without diabetes or hypertension but had a 15 minute episode of right face, arm and leg weakness, with speaking gibberish and not understanding speech. Gladstone et al. CMAJ 2004 R.H.Swartz, University of Toronto
3) Who to treat? Defining high risk. ABCD2 + MRI (DWI / intracranial vessel occlusions) Coutts et al., Int J. Stroke 2008; AnnNeurol 2005 R.H.Swartz, University of Toronto
The future of TIA Triaging? 1. 2. 3.
Secondary Prevention 4) What to treat? 1) Look at the intracranial vessels: atherosclerosis, moya-moya, inflammatory diseases 2) Look at the neck: Carotid stenosis, dissections 3) Look at the heart: Atrial fibrillation (+/- valve etc.) 4) Look at the blood: Platelet, APLA etc. 5) Look at the patient: risk factor modification (hypertension, high cholesterol, diabetes, smoking, drinking, diet/exercise, social situation) R.H.Swartz, University of Toronto
Percentage 3-Month Stroke Risk According to Etiological Subtype Lovett et al. Neurology 2004: meta-analysis, n=1709 20 19 15 10 9 12 5 3 0 small vessel unknown cardiac large vessel TOAST Classification (slide courtesy Dr. D. Gladstone)
What to treat: A) Symptomatic Carotid Stenosis Severe stenosis (70-99%) surgery highly beneficial (NNT=3*) Moderate stenosis (50-69%) surgery beneficial (NNT=7*) Mild stenosis (<50%) No surgery (slide courtesy Dr. D. Gladstone)
Timing of Carotid Surgery Rothwell et al. Lancet 2004 NNT to prevent one stroke at 5 years: NNT = 5 if surgery within 2 weeks NNT = 125 if surgery delayed >3 months! (slide courtesy Dr. D. Gladstone)
Management of Surgical Carotid Disease 2008 Canadian Best Practice Recommendations TIA or non-disabling stroke and ipsilateral 70% 99% ICA stenosis should be offered carotid endarterectomy within 2 weeks unless contraindicated Appropriate antiplatelet therapy depends on timing: Surgery in 24 hours: consider ASA Surgery in 1-2 weeks: consider combination ASA + clopidogrel Ensure optimal management of vascular risk factors * CMAJ 2008;179(12 Suppl):S1-S25.
What to treat? B) Atrial Fibrillation Atrial fibrillation (CHADS 2 ): Atrial fibrillation increases stroke risk 3-5x Higher risks: CHF, HTN, Age, DM, prior stroke/tia (2) CHADS Score Risk Stroke Rate / yr Recommendation 0 low <2 % ASA 75-325mg/d 1 low-mod <2 % warfarin INR 2-3 OR ASA 2 mod 4 % warfarin INR 2-3 3 high 5.9 % warfarin INR 2-3 4 v. high 8 18 % warfarin INR 2-3 Gage et al, JAMA 2001;285(22):2864-2870 R.H.Swartz, University of Toronto
Stroke Prevention R.H.Swartz, University of Toronto
Prevalence (%) Strokes Attributable to Atrial Fibrillation 30 20 AF prevalence Strokes attributable to AF 10 50 59 60 69 70 79 80 89 Age (years) Wolf, Stroke 1991;22:983-8 (slide courtesy Dr. F. Silver)
Warfarin: RRR in Stroke 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% SPINAF CAFA BAATAF SPAF I AFASK All Patients Hart RG Ann Intern Med 131:492-501, 1999
Gladstone et al, Stroke 2009
4) What to treat? C) Vascular risks Blood pressure: Common. >2/3 of adults >65 The most important modifiable risk factor (2-5 x) Ischemic, bleeding, silent strokes Contributes to: Large-vessel atherosclerotic disease Small-vessel (lacunar) disease LV dysfunction and Afib Untreated HTN increases stroke risk 3-4 times. Treatment can reduce stroke risk and fatalities ~40%. Most patients require 2 or more agents CHEP guidelines <140/90 (or if diabetes <130/80) Stroke. 2006;37:577-617 http://www.preventstroke.ca R.H.Swartz, University of Toronto http://www.americanheart.org/presenter.jhtml?identifier=4704
4) What to treat? C) Vascular risks Diabetes: ~2x increased risk of stroke. Highly correlated w/ HTN, high cholesterol, weight and sedentary lifestyles. Target HbA1c <0.07. Treatment reduces microvascular complications > macrovascular. Cholesterol: 2x increased risk of stroke. Risk for CAD (which independently also increases stroke risk). SPARCL (NNT = 50) http://www.americanheart.org/presenter.jhtml?identifier=4704 http://www.preventstroke.ca Stroke. 2006;37:577-617 R.H.Swartz, University of Toronto
4) What to treat? C) Vascular risks Smoking: 2 6 x risk (2x with second hand smoke only); normalizes >5 yrs, independent of age one-time advice from physician results in 2% of smokers quitting for >1 yr Weight loss, exercise, abdominal obesity: 2-6x increased stroke risk with obesity. Treatments: lowcalorie, low-fat, low-sodium diet, 20-30 minutes of moderate exercise most days http://www.preventstroke.ca R.H.Swartz, University of Toronto
4) What to treat? C) Vascular risks Anti-platelets (Aspirin (ASA), Clopidogrel (Plavix), ASA/ER-dipyridimol (Aggrenox)): Low-dose ASA 1 o prevention in people at risk increases GI bleed & hemorrhagic stroke risk. 75 160 mg daily as effective as higher doses. Stroke. 2006;37:577-617 http://www.americanheart.org/presenter.jhtml?identifier=4704 R.H.Swartz, University of Toronto
4) What to treat? C) Vascular risks Deciding between anti-platelets?! CAPRIE (ASA vs. Plavix), CURE (Plavix/ASA vs placebo/asa post-acs), ESPS2 and ESPRIT (ASA plus ER dipyridamole vs. ASA) MATCH (Plavix vs. ASA/plavix): bleeding higher w/ combined ASA/Plavix (risk increases with long-term use) PROFESS: no decisions between Plavix and Aggrenox Stroke. 2006;37:577-617 http://www.americanheart.org/presenter.jhtml?identifier=4704 R.H.Swartz, University of Toronto
Smoking cessation: Stroke Prevention 2 6 x increased risk (2x with second hand smoke); normalizes 5 yrs after quitting, independent of age one-time advice from physician results in 2% of smokers quitting for >1 yr Weight loss, exercise, abdominal obesity: 2-6x increased stroke risk with obesity. Treatments: lowcalorie, low-fat, low-sodium diet, 20-30 minutes of moderate exercise most days http://www.preventstroke.ca R.H.Swartz, University of Toronto
Stroke Prevention We will cure more people by aggressively managing risk factors than we will EVER cure with tpa. R.H.Swartz, University of Toronto
Secondary Prevention: What to treat? 1) Look at the intracranial vessels: atherosclerosis, moya-moya, inflammatory diseases 2) Look at the neck: Carotid stenosis, dissections 3) Look at the heart: Atrial fibrillation (+/- valve etc.) 4) Look at the blood: Platelet, APLA etc. 5) Look at the patient: risk factor modification (hypertension, high cholesterol, diabetes, smoking, drinking, diet/exercise, social situation) R.H.Swartz, University of Toronto
Summary: Stroke Prevention Strokes are common and serious We can identify high risk patients We have effective stroke prevention therapies But current management is often suboptimal Primary prevention: do the things we should do anyway Secondary prevention: Look at the brain vessels, neck, heart, blood and patient Treat TIA s early and aggressively Expedite surgery for symptomatic carotid artery disease Anticoagulate patients with atrial fibrillation Anti-platelets and other risk reduction for everyone else!