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Aspirin for Primary Prevention of Cardiovascular Disease

General Information

  • aspirin use for primary prevention of cardiovascular disease
    • generally recommended based on underlying cardiovascular disease risk profile
    • antithrombotic effects of aspirin mediated via acetylation of cyclooxygenase in platelets
    • low-dose aspirin suppresses platelet aggregation without affecting endothelial cell functions
    • major risk of chronic aspirin therapy includes gastrointestinal and less frequently intracranial bleeding
    • dose-related adverse effects include renal toxicity, gastrointestinal toxicity, and hypertension
    • aspirin should not be used in patients with
      • aspirin intolerance
      • increased risk of hemorrhagic stroke or gastrointestinal bleeding
    • Reference - aph100861573pa9h100861573pcxh100861573pmdc24573704pClin Med Res 2014 Dec;12(3-4):147



Recommendation grading systems used

  • United States Preventive Services Task Force (USPSTF) grades of recommendation (after July 2012)
    • Grade A - USPSTF recommends the service with high certainty of substantial net benefit
    • Grade B - USPSTF recommends the service with high certainty of moderate net benefit or moderate certainty of moderate-to-substantial net benefit
    • Grade C - USPSTF recommends selectively offering or providing the service (based on professional judgment and patient preference) with at least moderate certainty of small net benefit
    • Grade D - USPSTF recommends against providing the service with moderate-to-high certainty of no net benefit or harms outweighing benefits
    • Grade I - insufficient evidence to assess balance of benefits and harms
    • Reference - USPSTF Grade Definitions
  • American Diabetes Association (ADA) evidence grading system for clinical practice recommendations
    • Grade A
      • clear evidence from well-conducted, generalizable, randomized controlled trials (RCTs) that are adequately powered, including evidence from well-conducted multicenter trial or meta-analysis that incorporated quality ratings in analysis
      • compelling nonexperimental evidence, specifically, "all or none" rule developed by Center for Evidence Based Medicine at Oxford
      • supportive evidence from well-conducted RCTs that are adequately powered, including evidence from well-conducted trial at ≥ 1 institution or meta-analysis that incorporated quality ratings in analysis
    • Grade B
      • supportive evidence from well-conducted cohort studies, including evidence from well-conducted prospective cohort study or registry or meta-analysis of cohort studies
      • supportive evidence from a well-conducted case-control study
    • Grade C
      • supportive evidence from poorly controlled or uncontrolled studies
        • evidence from randomized clinical trials with ≥ 1 major or ≥ 3 minor methodologic flaws that could invalidate results
        • evidence from observational studies with high potential for bias (such as case series with comparison to historical controls)
        • evidence from case series or case reports
      • conflicting evidence with weight of evidence supporting recommendation
    • Grade E - expert consensus or clinical experience
    • Reference - ADA 2018 position statement on standards of medical care in diabetes: introduction (29222369Diabetes Care 2018 Jan;41(Suppl 1):S1)
  • American College of Cardiology/American Heart Association (ACC/AHA) 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 College of Cardiology/American Heart Association (ACC/AHA) grading system for recommendations
    • classes of recommendations
      • Class I (Strong) - should be performed or administered; indicated/useful/effective/beneficial
      • Class IIa (Moderate) - reasonable to perform or administer; can be useful/effective/beneficial
      • Class IIb (Weak) - may be considered; usefulness/effectiveness is unknown/unclear/uncertain or not well established
      • Class III: No Benefit (Moderate) - should not be performed or administered; not indicated/useful/effective/beneficial
      • Class III: Harm (Strong) - should not be performed or administered; potentially harmful, causes harm, or associated with excess morbidity/mortality
    • levels of evidence
      • Level A - high-quality evidence from > 1 randomized controlled trial (RCT), meta-analyses of high-quality RCTs, or ≥ 1 RCTs corroborated by high-quality registry studies
      • Level B-R - moderate-quality evidence from ≥ 1 RCTs or meta-analysis of moderate-quality RCTs
      • Level B-NR - moderate-quality evidence from ≥ 1 well-designed, well-executed nonrandomized studies, observational studies, or registry studies, or meta-analysis of such studies
      • Level C-LD - randomized or nonrandomized observational or registry studies with limitations of design or execution, meta-analyses of such studies, or physiological or mechanistic studies in human subjects
      • Level C-EO - consensus of expert opinion based on clinical experience
    • Reference - ACC/AHA guideline on primary prevention of cardiovascular disease (Circulation 2019 Mar 17. doi: 10.1161/CIR.0000000000000678 or J Am Coll Cardiol 2019 Mar 17. doi: 10.1016/j.jacc.2019.03.009
  • European Society of Cardiology (ESC) grading system for recommendations
    • classes of recommendations
      • Class I - evidence and/or general agreement that given treatment or procedure is beneficial, useful, and effective
      • Class II - conflicting evidence and/or divergence of opinion about usefulness/efficacy of given treatment or procedure
        • Class IIa - weight of evidence/opinion in favor of usefulness/efficacy
        • Class IIb - usefulness/efficacy less well established by evidence/opinion
      • Class III - evidence or general agreement that given treatment or procedure is not useful/effective, and in some cases may be harmful
    • levels of evidence
      • Level A - data derived from multiple randomized clinical trials or meta-analyses
      • Level B - data derived from single randomized clinical trial or large nonrandomized studies
      • Level C - consensus of opinion of experts and/or small studies, retrospective studies, registries
  • 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):53Sfull-text), commentary can be found in 23546508Chest 2013 Apr;143(4):1190
  • American Geriatrics Society (AGS) Beers Criteria grading system for recommendations
    • strength of recommendation
      • Strong - benefits clearly outweigh harms, adverse events, and risks, or harms, adverse events, and risks clearly outweigh benefits
      • Weak - benefits may not outweigh harms, adverse events, and risks
      • Insufficient - evidence inadequate to determine net harms, adverse events, and risks
    • quality of evidence
      • High - evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes, based on either
        • ≥ 2 consistent, higher-quality randomized controlled trials
        • multiple, consistent observational studies with no significant methodological flaws showing large effects
      • Moderate - evidence sufficient to determine risks of adverse outcomes
        • strength of evidence limited by any of
          • number, quality, size, or consistency of included studies
          • generalizability to routine practice
          • indirect nature of evidence on health outcomes
        • based on any of
          • ≥ 1 higher-quality trial with > 100 participants
          • ≥ 2 higher-quality trials with some inconsistency
          • ≥ 2 consistent, lower-quality trials
          • multiple, consistent observational studies with no significant methodological flaws showing at least moderate effects
      • Low - evidence insufficient to assess harms or risks in health outcomes due to any of
        • limited number or power of studies
        • large and unexplained inconsistency between higher-quality studies
        • important flaws in study design or conduct
        • gaps in chain of evidence
        • lack of information on important health outcomes
    • Reference - AGS 2015 updated Beers Criteria for potentially inappropriate medication use in older adults (26446832J Am Geriatr Soc 2015 Nov;63(11):2227), commentary can be found in 27100608J Am Geriatr Soc 2016 Apr;64(4):920

Synthesized Recommendation Grading System for DynaMed Content

  • The DynaMed Team 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 Methodology).
  • 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 users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed content, 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) 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 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 Team-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

  • DynaMed topics are created and maintained by the DynaMed Editorial Team and Process.
  • All editorial team members and reviewers have declared that they have no financial or other competing interests related to this topic, unless otherwise indicated.
  • DynaMed content includes Practice-Changing Updates, with support from our partners, McMaster University and F1000.

Special acknowledgements

  • 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 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 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. T114918, Aspirin for Primary Prevention of Cardiovascular Disease; [updated 2018 Nov 30, cited place cited date here]. Available from Registration and login required.

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EBSCO Information Services accepts no liability for advice or information given herein or errors/omissions in the text. It is merely intended as a general informational overview of the subject for the healthcare professional.


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