Evidence-Based Secondary Stroke Prevention and Adherence to Guidelines

Transcription

1 Evidence-Based Secondary Stroke Prevention and Adherence to Guidelines Mitchell S.V. Elkind, MD, MS Associate Professor of Neurology Columbia University New York, NY

2 Presenter Disclosure Information Mitchell S. V. Elkind, MD, MS, FAAN FINANCIAL DISCLOSURES: Research Funding: NINDS (K23 NS42912, R01 NS48134, R01 NS50724, R , P50 NS49060); BMS-Sanofi Partnership; Diadexus, Inc. Speakers Bureaus: Boehringer-Ingelheim, Inc.; BMS-Sanofi Partnership Consultant: Boehringer-Ingelheim, Inc.; Merck; GlaxoSmithKline; Amylin Pharmaceuticals UNLABELED/UNAPPROVED USES DISCLOSURE: None.

3 Stroke Death Rates per 100,000 US Adults Ages 35+, Age-adjusted Average Annual Deaths per 100,000 CDC National Center for Chronic Disease Prevention and Health Promotion

4 Krispy Kreme Store Locations Krispy Kreme Stores No Krispy Kreme Stores Krispy Kreme Web Site

5 Secondary Stroke Prevention Risk factor control Carotid endarterectomy and stenting Anti-coagulation Anti-platelet therapy

6 Meta-analysis of Stroke Reduction With Treatment of Hypertension % decrease Treated (n =18,487) Control (n =18,407) % decrease 0 All strokes Fatal strokes Collins R, et al. Lancet. 1990;335:

7 Epidemiological Link Between Blood Pressure Level and Incidence of Primary Stroke Results from 7 prospective observational studies (843 strokes) Stroke and Usual Diastolic Blood Pressure (in 5 categories defined by baseline DBP) Relative Risk of Stroke Baseline DBP category Approximate mean usual DBP Relative risk of stroke by approximate mean usual DBP in over 400,000 individuals without a history of acute myocardial infarction or stroke; 10-year follow-up up. MacMahon S, Peto R, Cutler J, et al. Lancet. 1990;335:

8 PROGRESS Collaborative Group. Lancet 2001; 358:

9 Stroke by Baseline BP Combination Therapy Active Events Placebo Hazard Ratio (95% CI) SBP > ( ) SBP ( ) SBP < ( ) DBP > ( ) DBP ( ) DBP < ( ) Total ( ) PROGRESS Collaborative Group. Lancet 2001; 358:

10 Preventing second stroke Effect of different antihypertensive classes Meta-analysis of 7 randomized clinical trials Much of the inter-class differences due to blood pressure reduction Risk reduction (%) β-antagonists ACE inhibitors Diuretics Diuretics + ACE inhibitors Rashid et al. Stroke 2003;34:

11 Secondary Stroke Prevention ASA 2006 Recommendations Antihypertensive treatment should be considered for patients with ischemic stroke or TIA, even in absence of a history of hypertension. (Class IIa, Level B) Benefit associated with average reduction of ~10/5 mm Hg and normal BP levels < 120/80 (JNC-7) (Class IIa, Level B) Optimal drug regimen uncertain: individualize treatment based on concomitant disease; consider diuretics and diuretic/acei combinations (Class I, Level A). For diabetics: ACEIs and ARBs are more effective in reducing the progression of renal disease and are recommended as first-choice medications (Class I, Level A). Sacco RL et al. Stroke 2006;37:

12 BP Control in the US: NHANES Trends in awareness, treatment, and control of high BP in adults ages (% s) Awareness Treatment Control JNC 7: Chobanian AV et al. JAMA 2003;289:

13 Lifestyle Modification Weight reduction Adopt DASH eating plan Dietary sodium reduction Physical activity Moderation of alcohol consumption 5 20 mmhg/10 kg 8 14 mmhg 2 8 mmhg 4 9 mmhg 2 4 mmhg Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)

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15 Stroke Prevention by Aggressive Reduction in Cholesterol Levels

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18 SPARCL Limitations Inclusion of patients with ICH Single statin (atorvastatin) Single dose (80 mg) Treatment not targeted to levels of LDL or other measures Treatment initiated at least 1 month after stroke

19 NCEP Guidelines Update 2004 In high-risk persons, the recommended LDL-C goal is <100 mg/dl. LDL-C goal <70 mg/dl is a therapeutic option on basis of available clinical trial evidence, especially for patients at very high risk. If LDL-C is > 100 mg/dl, an LDL-lowering drug is indicated simultaneously with lifestyle changes. If baseline LDL-C is <100 mg/dl, institution of an LDL-lowering drug to achieve an LDL-C level <70 mg/dl is a therapeutic option. If a high-risk person has high triglycerides or low HDL-C, consider combining a fibrate or nicotinic acid with an LDL-lowering drug. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy achieve at least a 30% to 40% reduction in LDL-C levels. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. TLC has the potential to reduce cardiovascular risk through several mechanisms beyond LDL lowering. Grundy et al. NCEP guidelines. Circulation 2004.

20 MRC/BHF Heart Protection Study SIMVASTATIN: MAJOR VASCULAR EVENT by PRIOR DISEASE SIMVASTATIN PLACEBO Rate ratio & 95% CI (10269) (10267) STATIN better PLACEBO better Previous MI Other CHD (not MI) No prior CHD CVD PVD Diabetes ALL PATIENTS 999 (23.5%) 1250 (29.4%) 460 (18.9%) 591 (24.2%) 172 (18.7%) 212 (23.6%) 327 (24.7%) 420 (30.5%) 276 (13.8%) 367 (18.6%) 2033 (19.8%) 2585 (25.2%) 24% SE 3 reduction (2P< ) HPS Collaborative Group. Lancet 2002;360:7.

21 National Cholesterol Education Program Adult Treatment Panel III (ATP III) CHD Risk Equivalents Risk for major coronary events equal to that in established CHD (10-year risk > 20%) Goal LDL < 100 mg/dl (now <70 mg/dl) Risk equivalents: 1. Diabetes mellitus 2. Multiple risk factors that confer a 10-year risk for CHD >20% 3. Other clinical forms of atherosclerotic disease (including symptomatic carotid artery disease) BUT WHAT ABOUT STROKE?

22 Risk of MI/Vascular Death (%) Kaplan-Meier survival curves for MI or vascular death, stratified by age and history of coronary artery disease (CAD) Years Follow ing Stroke Age > 70/CAD Age < 70/CAD Age > 70/no CAD Age < 70/no CAD Even in low risk group Risk still ~2% annually N Age < 70/no CAD N Age > 70/no CAD N Age < 70/CAD N Age > 70/CAD Dhamoon MS et al. Stroke 2007.

23 Risk of vascular events after first stroke in NOMASS Outcome 5-year (95% CI) 10-year estimate MI ( ) MI or vascular death ( ) MI or recurrent stroke or ( ) vascular death Dhamoon MS et al. Stroke 2007.

24 CHD Risk Equivalents Risk for major coronary events equal to that in established CHD (10-year risk > 20%) CHD AND STROKE Risk Equivalents Risk for major coronary events and stroke equal to that in established CHD (10-year risk > 20%) Elkind MSV. NEJM 2006;355:2369.

25 Poor adherence to lipid guidelines among stroke patients (VISP) Ovbiagele, B. et al. Neurology 2006;66:

26 System methods improve adherence to guidelines 1. Standardized, protocol-driven order entry 2. Disease management programs 3. Quality improvement initiatives

27 Secondary Stroke Prevention Risk factor control Carotid endarterectomy and stenting Anti-coagulation Anti-platelet therapy

28 Antithrombotic Therapy in Secondary Prevention for Patients with Atrial Fibrillation European Atrial Fibrillation Trial (EAFT) Relative Risk Reduction 80% 66% 60% 40% Anticoagulation vs. Placebo (INR 3-4.5) ASA 300mg vs. Placebo 20% 15% 0% EAFT Study Group. Lancet 1993;342:

29 Stroke Prevention - Non-cardioembolic ASA 2006 Recommendations For patients with noncardioembolic ischemic stroke or TIA, antiplatelet agents are recommended rather than oral anticoagulation to reduce the risk of recurrent stroke and other cardiovascular events (Class I, Evidence A). Sacco RL et al. Stroke 2006.

30 Warfarin versus Antiplatelet Therapy No evidence that warfarin is superior to aspirin for non-cardioembolic stroke WARSS Warfarin Aspirin Recurrent Stroke Study WASID Warfarin Aspirin Symptomatic Intracranial Disease ESPRIT European/Australasian Prevention of Reversible Ischemia Trial

31 Stroke Prevention - Non-cardioembolic ASA 2006 Recommendations Acceptable options for initial therapy (Class IIa, Level of Evidence A). aspirin ( mg qd) the combination of aspirin and extendedrelease dipyridamole (25/200 mg bid) clopidogrel (75 mg qd) Sacco RL et al. Stroke 2006.

32 Secondary Stroke Prevention ASA 2006 Recommendations The addition of aspirin to clopidogrel increases the risk of hemorrhage and is not routinely recommended for stroke or TIA patients. [Class III, Level A] For patients allergic to aspirin, clopidogrel is recommended.. [Class IIa, Level B]

33 ACCP Risk Stratification and Therapeutic Guidelines for AF Risk Level Patient Features Rx Guideline % of cases in GHC Low Age<65 y & no other RF ASA 15% Intermediate Age & no other RF ASA OR warfarin INR 2-3 8% High Any RF: CVA/TIA, age>75, CHF, Htn, DM Warfarin INR % Glazer, N. L. et al. Arch Intern Med 2007;167:

34 Use of antithrombotic therapy, overall and by American College of Chest Physicians (ACCP) stroke risk 41% Glazer, N. L. et al. Arch Intern Med 2007;167: Copyright restrictions may apply.

35 Reasons for Non-Adherence Patient-centered Physician-centered Systems-based

36 Conclusions Large randomized clinical trials have been conducted for secondary stroke prevention Detailed evidence-based guidelines for secondary stroke prevention exist Despite this, 30-40% of patients still fail to receive appropriate therapy Stay away from the Krispy Kremes!

37 Thanks for your attention!

38 Multivariable effect of antithrombotic guideline deviance on 1-year outcome. Results are reported as OR with 95% CI compared with the reference group guideline adherence (OR, 1). Nieuwlaat R et al. Am Heart J Jun;153(6):

39 Use of antithrombotic therapy by atrial fibrillation (AF) classification Glazer, N. L. et al. Arch Intern Med 2007;167: Copyright restrictions may apply.

40 Use of antithrombotic therapy by atrial fibrillation classification and American College of Chest Physicians (ACCP) stroke risk Glazer, N. L. et al. Arch Intern Med 2007;167: Copyright restrictions may apply.

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42 Alternatives to Evidence Based Medicine Eminence Based Medicine Eloquence Based Medicine Elegance Based Medicine Vehemence Based Medicine Confidence Based Medicine Nervousness Based Medicine Excellence Based Medicine With apologies to Isaacs D & Fitzgerald D. Seven alternatives to evidence based medicine. BMJ 1999;319(7225):1618.