Guidelines for prevention of stroke Guidelines for prevention of stroke


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  • Guidelines for prevention of stroke Guidelines for prevention of stroke

    1. 1. Guidelines for Prevention of Stroke in Patients with Ischemic Stroke or Transient Ischemic Attack From the Stroke Council of the AHA Ralph L. Sacco, Chair; Robert Adams, Vice-Chair Greg Albers, Mark J. Alberts, Oscar Benavente, Karen Furie, Larry B. Goldstein, Philip Gorelick, Jonathan Halperin, Robert Harbaugh, S. Claiborne Johnston, Irene Katzan, Margaret Kelly-Hayes, Edgar J. Kenton, Michael Marks, Lee H. Schwamm, Thomas Tomsick Stroke 2006;37:577-617
    2. 2. Presentation Compiled by the AHA/ASA Professional Education Committee Susan C. Fagan, Chair Deborah Bergman Glenn D. Graham S. Claiborne Johnston Karen Johnston Edgar J. Kenton Dawn Kleindorfer Creed Pettigrew Kathryn Taubert, Staff Scientist Karen Modesitt, Staff
    3. 3. Introduction This slide set was adapted from the AHA/ASA Guidelines for Prevention of Stroke in Patients with Ischemic Stroke or Transient Ischemic Attack. From the American Heart Association/American Stroke Association Council on Stroke Co-Sponsored by the Council on Cardiovascular Radiology and Intervention Affirmed by the American Academy of Neurology The full-text guidelines are available on the Web site of the AHA ( )
    4. 4. Introduction Since the 1999 AHA Stroke Council guidelines for the secondary prevention of stroke, important evidence from clinical trials has emerged that further supports and broadens the options for aggressive risk reduction therapies. The secondary prevention patient population to be addressed includes those with prior stroke or transient ischemic attack, regardless of etiology.
    5. 5. Changes from 1999 Guidelines <ul><li>1999 guidelines* DID NOT include levels of evidence </li></ul><ul><li>BP targets have been lowered to 120/80 </li></ul><ul><li>For diabetes, HbA1c <7%, rather than glucose <126 mg/dL is now targeted. </li></ul><ul><li>LDL <70 mg/dL now recommended for very-high- risk persons with multiple risk factors </li></ul><ul><li>Physical activity recommendations have been increased. </li></ul>* Wolf PA et al. Stroke 1999;30:1991-94
    6. 6. Changes from 1999 Guidelines <ul><li>Antiplatelet agents now the sole antithrombotic recommended for noncardioembolic stroke </li></ul><ul><li>Aspirin no longer solely recommended as first line </li></ul><ul><li>Ticlopidine no longer recommended as an option </li></ul><ul><li>New guidelines much more comprehensive </li></ul>Wolf PA et al. Stroke 1999;30:1991-94
    7. 7. Secondary Prevention Definition Therapy to reduce recurrent stroke and other cardiovascular events and decrease cardiovascular mortality in patients with previous stroke or TIA. Although prevention of stroke is of primary interest, many grades of recommendations were chosen to reflect the existing evidence on the reduction of all cardiovascular outcomes.
    8. 8. Transient Ischemic Attacks <ul><li>Guidelines now recognize TIA as an important harbinger of stroke. </li></ul><ul><li>- >10% 90-day risk of stroke after TIA </li></ul><ul><li>Prevention recommendations for patients with ischemic stroke are now broadly applied to those with TIA. </li></ul><ul><li>- Recognizes common etiologies and urgent need for treatment </li></ul>
    9. 9. AHA Classes and Levels of Evidence <ul><li>Class I Agreement the treatment is useful and effective </li></ul><ul><li>Class II Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a treatment. </li></ul><ul><ul><li>- Class IIa Weight of evidence is in favor of the treatment. </li></ul></ul><ul><li>- Class IIb Usefulness/efficacy is less well established by evidence </li></ul><ul><li>Class III Evidence and/or general agreement that the treatment is not useful/effective and in some cases may be harmful. </li></ul><ul><li>Levels of Evidence </li></ul><ul><li>A : Data derived from multiple randomized trials. </li></ul><ul><li>B : Data derived from a single randomized trial or nonrandomized studies. </li></ul><ul><li>C : Consensus opinion of experts. </li></ul>
    10. 10. Components of Secondary Prevention Diuretics +/- ACE inhibitors Statins Antiplatelet agents / anticoagulants Blood pressure control Diabetes management Lipid management Smoking cessation Alcohol moderation Weight reduction / physical activity Carotid artery Interventions
    11. 11. Challenges of Dissemination The committee acknowledges that strategies for implementation of the guidelines need to be developed and disparities in health care delivery addressed.
    12. 12. Blood Pressure Control ASA 2006 Secondary Stroke Recs <ul><li>Antihypertensives are recommended beyond the hyperacute period (Class I, Evidence A). </li></ul><ul><ul><li>- Benefit for those with & w/o HTN (Class IIa, Evidence B) </li></ul></ul><ul><ul><li>- Target BP level and reduction are uncertain, but normal BP levels are <120/80 by JNC-7* (Class IIa, Evidence B). </li></ul></ul><ul><li>Lifestyle modifications have been associated with BP reductions and should be included (Class IIb, Evidence C). </li></ul><ul><li>Optimal drug regimen uncertain; data support diuretics and the combination of diuretics and an ACEI (Class I, Evidence A). </li></ul>*Chobanian AV et al. JAMA 2003;289:2560-71.
    13. 13. <ul><li>Stroke </li></ul><ul><li>Combination 150/1770 255/1774 43% (30 to 54) </li></ul><ul><li>Single Drug 157/1281 165/1280 5% (-19 to 23) </li></ul><ul><li>Total Stroke 307/3051 420/3054 28% (17 to 38) </li></ul>PROGRESS Trial Results Combination versus Monotherapy Events active placebo Favors active Favors placebo Risk Reduction (95%CI) 0.4 1.0 2.0 Hazard Ratio PROGRESS Collaborative Group. Lancet 2001;358:1033-41
    14. 14. PROGRESS Trial Results Hypertensive versus Normotensive Patients Events/patients Active Placebo Favors active Favors placebo Risk reduction (95%CI) <ul><li>Stroke </li></ul><ul><li>Hypertensive 163/1464 235/1452 </li></ul><ul><li>Non-hypertensive 144/1587 185/1602 </li></ul><ul><li>Total stroke 307/3051 420/3054 </li></ul><ul><li>Major vascular events </li></ul><ul><li>Hypertensive 240/1464 331/1452 </li></ul><ul><li>Non-hypertensive 218/1587 273/1602 </li></ul><ul><li>Total events 458/3051 604/3054 </li></ul>32% (17 to 44) 27% (8 to 42) 28% (17 to 38) 29% (16 to 40) 24% (9 to 37) 26% (16 to 34) 0.5 1.0 Hazard ratio PROGRESS Collaborative Group. Lancet 2001;358:1033-41 2.0
    15. 15. Diabetes ASA 2006 Secondary Stroke Recs <ul><li>More rigorous control of HTN and dyslipidemia should be considered in patients with DM. </li></ul><ul><ul><li>BP targets of 130/80 mm Hg (Class IIa, Evidence B). ACEIs and ARBs are recommended as first-choice medications for patients with DM (Class I, Evidence A). </li></ul></ul><ul><li>Glucose control is recommended to near normoglycemic levels to reduce microvascular complications (Class I, Evidence A) and possibly macrovascular complications (Class IIb, Evidence B). </li></ul><ul><li>Hemoglobin A1c goal <7% (Class IIa, Evidence B). </li></ul>
    16. 16. Cholesterol Control ASA 2006 Secondary Stroke Recs <ul><li>Those with elevated chol, CHD, or evidence of an atherosclerotic origin should be managed according to NCEP III* (Class I, Evidence A). </li></ul><ul><li>Statins are recommended with target LDL-C of <100 mg/dL and <70 mg/dL for the very high–risk (Class I, Evidence A). </li></ul><ul><li>Those with no pre-existing indications for statins (nl chol levels, no CHD, or no atherosclerosis), are reasonable to consider for statins to reduce the risk of vascular events (Class IIa, Evidence B). </li></ul>*JAMA. 2001;285:2486-97
    17. 17. Cholesterol Control ASA 2006 Secondary Stroke Recs Heart Protection Study Collaborative Group. Lancet 2002;360:7-22 Baseline feature SIMVASTATIN (10269) PLACEBO (10267) Rate ratio & 95% CI STATIN better PLACEBO better Prior coronary disease Yes No 1459 1841 (21.8%) (27.5%) 574 744 (16.1%) (20.8%) Prior cerebrovascular disease Yes 406 488 (24.7%) (29.8%) No 1627 2097 (18.9%) (24.3%) Prior diabetes Yes 601 748 (20.2%) (25.1%) No 1432 1837 (19.6%) (25.2%) ALL PATIENTS 2033 2585 (19.8%) (25.2%) 0.4 0.6 0.8 1.0 1.2 1.4 24% SE 3 reduction (2P<0.00001)
    18. 18. HPS: Conclusions for people with cerebrovascular disease <ul><li>Lowering LDL cholesterol by 1 mmol/L (40 mg/dL) reduces the 5-year risk of ischemic stroke by about one quarter, with no apparent adverse effect on cerebral hemorrhage. </li></ul><ul><li>Similar proportional reductions in stroke risk are seen with statin therapy irrespective of age, sex, lipid levels, blood pressure, or use of other medications (including aspirin). </li></ul><ul><li>Statin therapy clearly reduces the risk of major vascular events among people with pre-existing cerebrovascular disease, irrespective of the presence of coronary disease. </li></ul>Heart Protection Study Collaborative Group. Lancet 2002;360:7-22
    19. 19. Recommendations for Modifiable Behavioral Risk Factors <ul><li>Smoking : All ischemic stroke or TIA patients who smoked in the past should be encouraged not to smoke (Class I, Level C). </li></ul><ul><li>Alcohol : Patients with prior ischemic stroke or TIA who are heavy drinkers should eliminate or reduce their consumption of alcohol (Class I, Level A). </li></ul><ul><li>Obesity : Weight reduction may be considered for all overweight ischemic stroke or TIA patients to maintain the goal BMI (Class IIb, Level C). </li></ul><ul><li>Physical activity : Substantial evidence exists that physical activity exerts a beneficial effect on multiple cardiovascular risk factors including those for stroke (Class IIB, Level C). </li></ul>
    20. 20. Symptomatic Carotid Endarterectomy ASA 2006 Secondary Stroke Recs <ul><li>Ipsilateral severe (70% to 99%) carotid stenosis, CEA is recommended (Class I, Evidence A). </li></ul><ul><li>Ipsilateral moderate (50% to 69%) carotid stenosis, CEA is recommended depending on age, gender, comorbidities, and the severity of symptoms (Class I, Evidence A). </li></ul><ul><li>Stenosis <50% , there is no indication for CEA (Class III, Evidence A). </li></ul>
    21. 21. Urgent Endarterectomy Surgery within 2 weeks is suggested rather than delaying surgery (Class IIa, Evidence B). Rothwell PM. Lancet 2004;363(9413):915-24
    22. 22. Carotid Angioplasty and Stenting ASA 2006 Secondary Stroke Recs <ul><li>CAS may be considered (Class IIb, Evidence B). </li></ul><ul><li>- Stenosis (>70%) difficult to access surgically </li></ul><ul><li>- Medical conditions that greatly increase the risk for surgery, or </li></ul><ul><li>- When other circumstances exist such as radiation-induced stenosis or restenosis after CEA. </li></ul><ul><li>CAS is reasonable when performed by operators with morbidity and mortality rates of 4% to 6% (Class IIa, Evidence B). </li></ul>
    23. 23. Atrial Fibrillation ASA 2006 Recommendations <ul><li>For patients with ischemic stroke or TIA with persistent or paroxysmal (intermittent) AF , anticoagulation with adjusted-dose warfarin (target INR 2.5, range 2.0 to 3.0) is recommended (Class I, Evidence A). </li></ul><ul><li>For patients unable to take oral anticoagulants, aspirin 325 mg per day is recommended (Class I, Evidence A). </li></ul>
    24. 24. 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).
    25. 25. Warfarin-Aspirin for Recurrent Stroke Study (WARSS) 0 90 180 270 360 450 540 630 720 Days After Randomization 0 10 20 30 Probability of Event (%) Warfarin Aspirin 1.13 Hazard Ratio P= 0.25 The primary outcome occurred in 17.8% of patients in the warfarin group and 16.0% in the ASA group. Mohr JP et al. N Engl J Med 2001;345:1444-51 900 932 951 974 984 1004 1032 1057 1103 Aspirin 885 924 939 956 972 998 1013 1047 1103 Warfarin No. at Risk
    26. 26. Stroke Prevention: Non-cardioembolic ASA 2006 Recommendations <ul><li>Acceptable options for initial therapy </li></ul><ul><ul><li>(Class IIa, Evidence A). </li></ul></ul><ul><li>- aspirin (50-325 mg qd) </li></ul><ul><li>- the combination of aspirin and extended- release dipyridamole (25/200 mg bid) </li></ul><ul><li>- clopidogrel (75 mg qd) </li></ul>
    27. 27. Antiplatelet Therapy ASA 2006 Recommendations <ul><li>Compared to aspirin alone, both the combination of aspirin and extended-release dipyridamole and clopidogrel are safe. </li></ul><ul><li>The combination of aspirin and extended-release dipyridamole is suggested instead of aspirin alone (Class IIa, Level A). </li></ul><ul><li>Clopidogrel is suggested instead of aspirin alone based on direct comparison trials </li></ul><ul><li>(Class IIb, Level B). </li></ul>
    28. 28. ESPS 2: Effects on Stroke—Relative Risk Reduction (Pair-wise Comparisons) 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% 40.0% 37.0% P < 0.001 16.3% P = 0.039 18.1% P = 0.013 23.1% P = 0.006 ER-DP = Extended-Release Dipyridamole ASA = Acetylsalicylic Acid RRR = Relative Risk Reduction RRR ASA/ER-DP vs. Placebo ER-DP vs. Placebo ASA vs. Placebo ASA/ER-DP vs. ASA ESPS 2 Group. J Neurol Sci 1997;151(suppl):S1-S77
    29. 29. Efficacy of Clopidogrel vs Aspirin in MI, Ischemic Stroke, or Vascular Death (n=19,185) CAPRIE Study Months of Follow-up Cumulative Event Rate (%) 0 4 8 12 16 Clopidogrel Aspirin Overall Relative Risk Reduction 8.7%* 3 6 9 12 15 18 21 24 27 30 33 36 Aspirin 5.83% 5.32% Clopidogrel Event Rate per Year *ITT analysis. CAPRIE Steering Committee. Lancet 1996;348:1329-39
    30. 30. Secondary Stroke Prevention ASA 2006 Recommendations <ul><li>Insufficient data are available to make evidence-based recommendations regarding choices between antiplatelet options other than aspirin. Selection of an antiplatelet agent should be individualized based on patient risk factor profiles, tolerance, and other clinical characteristics. </li></ul>
    31. 31. Secondary Stroke Prevention ASA 2006 Recommendations <ul><li>The addition of aspirin to clopidogrel increases the risk of hemorrhage and is not routinely recommended for stroke or TIA patients (Class III, Evidence A). </li></ul><ul><li>For patients allergic to aspirin, clopidogrel is recommended (Class IIa, Evidence B). </li></ul>
    32. 32. MATCH Trial Primary End Point: MI, IS, Vascular Death, or Rehospitalization for an Acute Ischemic Event Overall Relative Risk Reduction 6.4%* P = 0.244 *ITT Analysis Cumulative Event Rate Clopidogrel + ASA Clopidogrel + Placebo 0.00 0.04 0.08 0.12 0.16 0.20 0 3 6 9 12 15 18 N=7,599 Months of Follow Up Diener H-C et al. Lancet 2004;364:331-7
    33. 33. MATCH: Safety Outcomes <ul><li>Excess life-threatening bleeding events with combination versus clopidogrel monotherapy: </li></ul><ul><li>96 (2.6%) vs. 49 (1.3%); p<0.0001 </li></ul><ul><li>Excess minor bleeds with combination therapy versus clopidogrel alone: </li></ul><ul><li>120 (3.2%) vs. 39 (1.0%); p<0.0001 </li></ul>Diener H-C et al. Lancet 2004;364:331-7
    34. 34. Secondary Stroke Prevention ASA 2006 Recommendations <ul><li>For patients who have an ischemic cerebrovascular event while taking aspirin , there is no reliable evidence that increasing the dose of aspirin provides additional benefit. Although alternative antiplatelet agents are often considered for these patients, no single agent or combination has been specifically evaluated in patients who have had an event while receiving aspirin. </li></ul>
    35. 35. Stroke and Pregnancy ASA 2006 Secondary Stroke Recs <ul><li>High-risk thromboembolic conditions consider: </li></ul><ul><li>- adjusted-dose UFH throughout pregnancy, </li></ul><ul><li>- adjusted-dose LMWH with Factor Xa monitoring </li></ul><ul><li>- UFH or LMWH until week 13, followed by warfarin until mid-3rd trimester, then UFH or LMWH in last trimester (Class IIb, Evidence C). </li></ul><ul><li>Lower risk conditions </li></ul><ul><li>- UFH or LMWH in the first trimester followed by - low-dose aspirin for the remainder of the pregnancy (Class IIb, Evidence C). </li></ul>
    36. 36. Adjusted Relative Risk of Stroke According to a Woman’s Status With Respect to Pregnancy* * Relative risks have been adjusted for age and race; † The 6-week period after pregnancy was defined as the 6 weeks after a spontaneous or induced abortion, stillbirth, or live birth; ‡ Subarachnoid hemorrhages (SAHs) have been excluded. During pregnancy or 6 weeks 1.6 (1.0-2.7) 5.6 (3.0-10.5) 2.4 (1.6-3.6) After pregnancy During pregnancy 0.7 (0.3-1.6) 2.5 (1.0-6.4) 1.1 (0.6-2.0) During 6 weeks after pregnancy 5.4 (2.9-10.0) 18.2 (8.7-38.1) 7.9 (5.0-12.7) After delivery 8.7 (4.6-16.7) 28.3 (13.0-61.4) 12.7 (7.8-20.7) After abortion 1.1 (0.2-7.9) 4.5 (0.6-33.1) 1.8 (0.4-7.2) RR of RR of RR of Cerebral Intracerebral Either Type Infarction Hemorrhage of Stroke ‡ Risk Period † (95% CI) (95% CI) (95% CI) Kittner SJ et al. (1996), N Engl J Med 335(11):768-774
    37. 37. Postmenopausal Hormones ASA 2006 Secondary Stroke Recs For women with ischemic stroke or TIA, postmenopausal hormone therapy (with estrogen with or without a progestin) is not recommended (Class III, Evidence A).
    38. 38. Women’s Health Initiative <ul><li>16,608 postmenopausal women, 50-79 years, with an intact uterus at baseline were recruited by 40 U.S. clinical centers for the period 1993-1998. </li></ul><ul><li>Received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). </li></ul><ul><li>After a mean of 5.2 years of follow-up, the trial was stopped because of high rates of invasive breast cancer and the global index statistic supported risks exceeding benefits. </li></ul>Rossouw et al. JAMA 2002;288(3):321-33
    39. 39. Estimates of Cumulative Hazards for Strokes in Women’s Health Initiative Study Time (Years) Cumulative Hazard 0.030 0.025 0.020 0 1 2 3 4 5 6 7 0.015 0.010 0.005 0 Estrogen + Progestin Placebo Rossouw et al. JAMA 2002;288(3):321-33
    40. 40. Other Circumstances ASA 2006 Secondary Stroke Recs <ul><li>Dissections </li></ul><ul><li>PFO and hyperhomocysteinemia </li></ul><ul><li>Hypercoagulable states </li></ul><ul><li>Sickle cell disease </li></ul><ul><li>Cerebral venous thrombosis </li></ul><ul><li>Anticoagulation after cerebral hemorrhage </li></ul>
    41. 41. Level A Recommendations <ul><li>Antihypertensive treatment </li></ul><ul><li>Glucose control to reduce microvascular complications of diabetes </li></ul><ul><li>Statins to reduce LDL to <100 or <70 for high-risk patients (sympt CHD or athero) </li></ul><ul><li>CEA for sympt 50-99% </li></ul><ul><li>NO CEA for <50% sympt stenosis </li></ul><ul><li>Warfarin at INR 2.5 for Afib. (ASA if unable) </li></ul><ul><li>Antiplatelet for noncardioembolic </li></ul><ul><li>NO combination clopidogrel and ASA </li></ul>
    42. 42. Summary <ul><li>These guidelines provide comprehensive and timely evidence-based recommendations. </li></ul><ul><li>There is an intent to fully update the guidelines every 3 years, with updates encouraged when pivotal studies are published. </li></ul>