Secondary Stroke Prevention Luke Bradbury, MD 10/4/14 Fall WAPA Conferfence

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1 Guidelines Secondary Stroke Prevention Luke Bradbury, MD 10/4/14 Fall WAPA Conferfence Stroke/TIA Nearly 700,000 ischemic strokes and 240,000 TIAs every year in the United States Currently, the risk for stroke recurrence is ~3-4% Hong, et al; Declining Stroke and Vascular Event Recurrence Rates in Secondary Prevention Trials Over the Past 50 Years and Consequences for Current Trial Design; Circulation.2011; 123: Hypertension > 70% of patients with recent strokes suffer from hypertension As blood pressure increases, risk of first stroke increases May start as low as systolic > 115 PROGRESS trial 2001 study in Asia, Australia, and Europe; 6105 subjects Compared perindopril ± indapamide vs placebo Treatment arm annual stroke risk reduced from 3.8% to 2.7% (over four years 14% to 10%) Relative Risk Reduction 28% 1

2 Guideline Recommendations Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack (PROGRESS); Lancet 2001; 358: Primary prevention in class I hypertension (>140/>90) Still to initiate treatment in all individuals (might change for individuals 60 with no other problems) Secondary prevention in class I hypertension Already end organ damage, so everyone is treated; but for patients with <140/<90, benefit is uncertain Target Large randomized trials do not show an obvious benefit for lower targets (systolic <120 vs <140) Official recommendations are for <140/<90 Hypertension: What do use? Diuretics and/or ACE-inhibitors generally used Diuretics alone with or without ACE-I with proven efficacy Calcium channel blockers, beta blockers, reninangiotensin converting enzyme inhibitors (ACE- I/ARB) used as monotherapy seem to be less effective, but these studies are generally not powered very well Cholesterol Cholesterol High-intensity statin therapy recommended for patients with stroke/tia of atherosclerotic origin with an LDL >100 Newer guidelines also recommend it for patients with LDL <100 (target?) 2

3 Cholesterol SPARCL Atorvastatin 80 mg daily vs placebo Reduced second stroke/tia; hazard ratio was 0.77 Myalgias 5.5% in treatment group 6.0% in placebo group High-Dose Atorvastatin after Stroke or Transient Ischemic Attack (SPARCL); NEJM 355;6 Diabetes 26.9% of adults 65 have diagnosed or occult DM In patients with known cerebrovascular disease 60-70% have either pre-dm or DM Patients with DM have a 60% increased risk for recurrent stroke Diabetes No large trials for DM management after stroke are available to help guide treatment So far no trial has clearly shown greater efficacy of one drug over another Metformin, pioglitazone, and linaglipitide may be good Insulin Resistance Interventoin After Stroke (IRIS) trial is ongoing and may help Diabetes Recommendations: HgA1c, fasting glucose, or oral glucose tolerance test is needed; HgA1c is preferred For patients with pre-dm or DM, the ADA guidelines or glycemic control are recommended Obesity Clearly increases the risk of a primary stroke BMI: starts to increase above 20 Central obesity is more of a risk than general obesity But for secondary strokes? Not clear; some recent studies suggest that obese patients with stroke have a lower risk for major vascular events than lean patients 3

4 Obesity Recommendations Screen patients; but despite the clear benefit on other risk factors (dyslipidemia, DM, hypertension, and inflammation) weight loss for secondary stroke prevention is uncertain Activity Moderate to vigorous aerobic activity is recommended 3-4/week; average 40 minutes each session With disabilities from the stroke, the regimen should be initiated under the supervision of a certified physical therapist Nutrition Nutrition Routine vitamin supplementation has not been shown to be effective Hyperhomocysteinemia with low B12 may benefit from B12 therapy Mediterranean-type diet may be helpful, even compared to low-fat diets Fish, fruits, vegetables, nuts, olive oil Obstructive Sleep Apnea All stroke/tia patients should be screened and a sleep study considered Outcomes may be better with CPAP, but studies are underway Cigarette Smoking Don t 4

5 Alcohol Heavy alcohol use increases risk for second stroke 2 drinks for men and 1 for women may be reasonable but if the patient does not drink they should not be counseled to start Carotid Artery Disease If <50%, no surgery or stenting is recommended 50-69% carotid endarterectomy is recommended depending on patient characteristics (favorable surgical risk) 70% should have CEA Carotid Stent vs CEA CREST 2502 patients enrolled CAS group had 1262 CEA group had 1240 Stenting versus Endarterectomy for Treatment of Carotid-Artery Stenosis; NEJM 2010 CREST Periprocedural strokes were less common in CEA group, MI was more common in CAS group Large review of CREST and other trials (7572 total patients) showed that periprocedural complications were more common with CAS (namely death and stroke) Carotid Stenosis When to operate With minor stroke and TIA < 2 weeks is recommended Many patients can have it on the same admission for their stroke/tia Stenting may be better in younger patients or patients with difficult anatomy, contralateral occlusion, or high risk for surgical complications 5

6 Intracranial Atherosclerosis Medical management (statin, antiplatelet, lifestyle modification) is preferred to stenting Aspirin 325 mg is preferred over warfarin Adding clopidogrel for 90 days might be reasonable Atrial Fibrillation Responsible for 10-12% of all ischemic strokes, much more in older populations Often paroxysmal with no clinical symptoms Monitoring for 30 days is now reasonable Outpatient monitoring Atrial fibrillation Anticoagulation is recommended with warfarin, dabigatran (Pradaxa), apixaban (Eliquis), rivaroxaban (Xarelto) Newer anticoagulants No diet interactions, fewer medication interactions, no need for monitoring, immediately therapeutic No ability to rapidly reverse (yet) Atrial Fibrillation For patients who cannot take anticoagulants Aspirin is recommended, and aspirin plus clopidogrel is reasonable though the bleeding risk is higher When to start anticoagulation Generally safe within 14 days but can be delayed beyond that if there is high risk hemorrhagic conversion 6

7 Antiplatelet therapy for lacunar strokes Not a lot of great data to go by, but in general: Aspirin monotherapy or aspirin-dipyridomole (Aggrenox) is recommended after TIA or stroke (anticoagulation is not recommended) Aspirin and clopidogrel Aspirin + clopidogrel can be considered if started within 24 hours of minor stroke/tia and continued for three months Clopidogrel monotherapy is reasonable for patients who cannot take aspirin Aspirin and clopidogrel should NOT be started days or years after minor stroke or TIA (bleeding risk outweighs benefit) Aspirin already on board Increasing the dose from 81 mg does not provide additional benefit Not enough evidence to clearly show that adding another agent is helpful Patent Foramen Ovale 15-25% of the population has a PFO Little data, but anticoagulation is probably no better than antiplatelet therapy Unless there is a venous source of the embolism No clear benefit from PFO closure at this point Questions? 7

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