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Antiplatelet Therapy for Secondary Prevention of Stroke

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AssignmentLatePractice Changing | Updated 15 Jul 2019

reduction in risk of major ischemic events with clopidogrel plus aspirin compared to aspirin alone may be limited to first 21 days of treatment after stroke or TIA (Circulation 2019 Jun 26 early online)

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General Information

  • definitions
    • stroke - sudden loss of focal neurological function due to infarction or hemorrhage in the brain, retina, or spinal cord, with symptoms lasting > 24 hours (or death within 24 hours) or of any duration if imaging or autopsy shows focal infarction or hemorrhage relevant to the symptoms
    • transient ischemic attack (TIA) - similar to stroke but with symptoms lasting < 24 hours and with no imaging evidence of infarction
    • ischemic stroke - stroke due to embolism from heart, artery, or small vessel disease
    • hemorrhagic stroke - stroke due to bleeding, most commonly as a result of hypertension, cerebral amyloid angiopathy, anticoagulation, or vascular structural lesions
    • Reference - 27637676Lancet 2017 Feb 11;389(10069):641OpenInNew
  • patients who have had a stroke or TIA are at risk of recurrent stroke

References

General references used

  1. Lansberg MG, O'Donnell MJ, Khatri P, et al; American College of Chest Physicians. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, Ninth Edition: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e601S-36SOpenInNewfull-textOpenInNew
  2. Kernan WN, Ovbiagele B, Black HR, et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 Jul;45(7):2160-236OpenInNew, correction can be found in Stroke 2015 Feb;46(2):e54OpenInNew, commentary can be found in Stroke 2015 Apr;46(4):e85OpenInNew
  3. National Institute for Health and Clinical Excellence. Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events. Review of NICE technology appraisal guidance 90. NICE 2010 Dec:TA210OpenInNewPDFPictureAsPdf
  4. Wein T, Gladstone D, on behalf of Canadian Stroke Best Practices and Standards Working Group. Canadian Best Practice Recommendations, Sixth Edition, Chapter Three, Secondary Prevention of Stroke Recommendations. CSN 2017 OctOpenInNew
  5. Powers WJ, Rabinstein AA, Ackerson T, et al, American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110OpenInNew, corrections can be found in Stroke 2018 Mar;49(3):e138OpenInNew and Stroke 2018 Jun;49(6):e233OpenInNew

Recommendation grading systems used

  • British Committee for Standards in Haematology (BCSH) guideline grading system
    • strength of recommendation
      • Grade 1
        • strong recommendations made when there is confidence that benefits do or do not outweigh harm and burden
        • can be applied uniformly to most patients
        • regard as "recommend"
      • Grade 2
        • weak recommendations made where benefits and risks and burdens are closely balanced or magnitude of benefits and risks is less certain
        • require judicious application to individual patients based on patient values and preferences
        • regard as "suggest"
    • quality of evidence
      • A - high
        • further research very unlikely to change confidence in estimate of effect
        • based on randomized trials without important limitations
      • B - moderate
        • further research may well have important impact on confidence in estimate of effect and may change estimate
        • based on randomized trials with important limitations or very strong evidence from observational studies
      • C - low
        • further research likely to have important impact on confidence in estimate of effect and likely to change estimate
        • based on observational studies
      • D - very low
        • any estimate of effect is very uncertain
        • based on any other evidence
    • Reference - BCSH Grading of Recommendations Assessment, Development and Evaluation (GRADE) systemPictureAsPdf
  • American College of Chest Physicians (ACCP) grades
    • Grade 1 - strong recommendation based on clear risk/benefit balance
    • Grade 2 - weak recommendation based on unclear or close risk/benefit balance
    • Grade A - high-quality evidence based on consistent evidence from randomized trials without important limitations or exceptionally strong evidence from observational studies
    • Grade B - moderate-quality evidence based on randomized trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise results) or very strong evidence from observational studies
    • Grade C - low- or very low-quality evidence based on evidence for ≥ 1 critical outcome from observational studies, case series, or randomized trials with serious flaws or indirect evidence
    • Reference - ACCP evidence-based clinical practice guideline on methodology for development of antithrombotic therapy and prevention of thrombosis (22315256Chest 2012 Feb;141(2 Suppl):53SOpenInNewfull-textOpenInNew), commentary can be found in 23546508Chest 2013 Apr;143(4):1190OpenInNew
  • Canadian Stroke Best Practice Recommendations (CSBPR) levels of evidence
    • Evidence Level A
      • meta-analysis of randomized controlled trials or consistent findings from ≥ 2 randomized trials
      • desirable effects clearly outweigh undesirable effects or vice versa
    • Evidence Level B
      • single randomized controlled trial or consistent findings from ≥ 2 well-designed nonrandomized and/or uncontrolled trials, and large observational studies
      • meta-analysis of nonrandomized and/or observational studies
      • desirable effects outweigh or are closely balanced with undesirable effects or vice versa
    • Evidence Level C
      • writing group consensus and/or supported by limited research evidence
      • desirable effects outweigh or are closely balanced with undesirable effects or vice versa
    • Clinical consideration - reasonable practical advice provided by consensus of the writing group on specific clinical issues that are common and/or controversial and lack research evidence to guide practice.
    • Reference - Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke (CSN 2017 OctOpenInNew)
  • American Heart Association/American Stroke Society (AHA/ASA) 2014 grading system for recommendations
    • classifications of recommendations
      • Class I - procedure or treatment should be performed or administered
      • Class IIa - reasonable to perform procedure or administer treatment, but additional studies with focused objectives needed
      • Class IIb - procedure or treatment may be considered; additional studies with broad objectives needed, additional registry data would be useful
      • Class III - procedure or treatment should not be performed or administered because it is not helpful or may be harmful
        • Class III ratings may be subclassified as Class III No Benefit or Class III Harm
    • levels of evidence
      • Level A - data derived from multiple randomized clinical trials or meta-analyses
      • Level B - data derived from single randomized trial or nonrandomized studies
      • Level C - only expert opinion, case studies, or standard of care
  • American Heart Association/American Stroke Society (AHA/ASA) 2018 grading system for recommendations
    • classifications of recommendations
      • Class I - procedure or treatment should be performed or administered
      • Class IIa - reasonable to perform procedure or administer treatment, but additional studies with focused objectives needed
      • Class IIb - procedure or treatment may be considered; additional studies with broad objectives needed, additional registry data would be useful
      • Class III - procedure or treatment should not be performed or administered because it is not helpful or may be harmful
        • Class III ratings may be subclassified as Class III No Benefit or Class III Harm
    • levels of evidence
      • Level A - high-quality evidence from > 1 randomized controlled trial or meta-analysis of high-quality randomized controlled trials
      • Level B-R - moderate-quality evidence from ≥ 1 randomized controlled trial or meta-analysis of moderate-quality randomized controlled trials
      • Level B-NR - moderate-quality evidence from ≥ 1 well-designed nonrandomized trial, observational studies, or registry studies, or meta-analysis of such studies
      • Level C-LD - randomized or nonrandomized studies with methodological limitations or meta-analyses of such studies
      • Level C-EO - consensus of expert opinion based on clinical experience

Synthesized Recommendation Grading System for DynaMed

  • DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based MethodologyOpenInNew).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed (DM), we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)OpenInNew to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed (DM) synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

Special acknowledgements

  • Andrew N. Russman, DO (Cerebrovascular Center Neurological Institute, and Orthopedic Surgery Orthopedic and Rheumatologic Institute, Cleveland Clinic; Ohio, United States)
  • Dr. Russman declares a relevant financial relationship with Boston Scientific (Consultant).
  • Esther Jolanda van Zuuren, MD (Head of Allergy, Dermatology, and Venereology, Leiden University Medical Centre; Netherlands)
  • Dr. van Zuuren declares no relevant financial conflicts of interest.
  • Alexander Rae-Grant, MD, FRCPC, FAAN (Deputy Editor, Neurology DynaMed Plus; Neurologist, Cleveland Clinic; Ohio, United States)
  • Dr. Rae-Grant declares no relevant financial conflicts of interest.
  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of DynaMed Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T163233, Antiplatelet Therapy for Secondary Prevention of Stroke; [updated 2018 Nov 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T163233. Registration and login required.
  • KeyboardArrowRight

    Overview and Recommendations

    • Background

    • Evaluation

    • Management

  • Related Summaries

  • General Information

  • KeyboardArrowRight

    Recommendations from Professional Organizations

    • American Heart Association/American Stroke Association (AHA/ASA) 2014 and 2018 guidelines for patients with stroke or transient ischemic attack

    • Canadian Stroke Best Practice Recommendations (CSBPR) 2017 recommendations

    • American College of Chest Physicians (ACCP) 2012 guidelines

    • National Institute for Health and Clinical Excellence (NICE) recommendations

  • KeyboardArrowRight

    Aspirin Monotherapy

    • Recommendations from professional organizations

    • Evidence

  • KeyboardArrowRight

    Clopidogrel Monotherapy

    • Mechanism of action and adverse events

    • Recommendations from professional organizations

    • Evidence

  • KeyboardArrowRight

    Clopidogrel Plus Aspirin

    • Recommendations from professional organizations

    • Evidence

  • KeyboardArrowRight

    Dipyridamole Plus Aspirin

    • Recommendations from professional organizations for use of dipyridamole for secondary prevention of stroke

    • Evidence

  • KeyboardArrowRight

    Other Antiplatelet Regimens

    • KeyboardArrowRight

      Cilostazol monotherapy

      • Recommendations from professional organizations

      • Evidence

    • Triple therapy

    • P2Y12 inhibitors other than clopidogrel

    • Other antiplatelet agents

  • KeyboardArrowRight

    Specific Clinical Situations

    • Cardioembolic ischemic stroke

    • Aortic arch atheroma

    • Intracranial atherosclerosis

    • Intracerebral hemorrhage

    • Periprocedural considerations

    • Ischemic stroke while on antiplatelet therapy

    • Antiplatelet resistance

    • Drug interactions

    • Other clinical situations

  • KeyboardArrowRight

    Quality Improvement

    • Physician Quality Reporting System Quality Measures

  • KeyboardArrowRight

    Guidelines and Resources

    • KeyboardArrowRight

      Guidelines

      • United States guidelines

      • United Kingdom guidelines

      • Canadian guidelines

      • European guidelines

      • Asian guidelines

      • Mexican guidelines

    • Review articles

  • Patient Information

  • KeyboardArrowRight

    References

    • General references used

    • Recommendation grading systems used

    • Synthesized Recommendation Grading System for DynaMed

    • DynaMed Editorial Process

    • Special acknowledgements

    • How to cite

Topic Editor
Andrew N. Russman DO
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Affiliations

Cerebrovascular Center Neurological Institute, and Orthopedic Surgery Orthopedic and Rheumatologic Institute, Cleveland Clinic; Ohio, United States

Conflicts of Interest

Dr. Russman declares a relevant financial relationship with Boston Scientific (Consultant).

Recommendations Editor
Esther Jolanda van Zuuren MD
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Affiliations

Head of Allergy, Dermatology, and Venereology, Leiden University Medical Centre; Netherlands

Conflicts of Interest

Dr. van Zuuren declares no relevant financial conflicts of interest.

Deputy Editor
Alexander Rae-Grant MD, FRCPC, FAAN
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Affiliations

Deputy Editor Neurology, DynaMed Plus; Massachusetts, United States; Neurologist, Cleveland Clinic; Ohio, United States

Conflicts of Interest

Dr. Rae-Grant declares no relevant financial conflicts of interest.

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