2 ACC Prevention Antiplatelet and Anticoagulant

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  • The Evidence for Current Cardiovascular Disease Prevention Guidelines: Antiplatelet and Anticoagulation Therapy Evidence and GuidelinesAmerican College of Cardiology Best Practice Quality Initiative Subcommittee and Prevention Committee

  • Classification of Recommendations and Levels of Evidence*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.

    In 2003, the ACC/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this will increase readers comprehension of the guidelines and will allow queries at the individual recommendation level.

  • Icons Representing the Classification and Evidence Levels for Recommendations

  • Antiplatelet Therapy Evidence and GuidelinesEvidence for Current Cardiovascular Disease Prevention Guidelines

  • Collagen Thrombin TXA2ADPADP=Adenosine diphosphate, COX=Cyclooxygenase, TXA2=Thromboxane A2Clopidogrel bisulfateTXA2PhosphodiesteraseADPActivationCOXTiclopidine hydrochlorideAspirinGp 2b/3a InhibitorsDipyridamoleSource: Schafer AI. Antiplatelet Therapy. Am J Med 1996;101:199209Prasugrel hydrochlorideAntiplatelet Therapy:TargetsTicagrelor

  • Sources: 1Pearson TA, et al. Circulation, 2002;106:388-3912Mosca L, et al. Circulation, 2007;115:1481-1501 3 Smith SC Jr. et al. JACC 2011;58:2432-24464http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/19-979S018_Ticlid_prntlbl.pdf5http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020839s042lbl.pdf6http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022307s001lbl.pdf7http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM221383.pdfAntiplatelet Therapy:Common Oral Agents*81 mg is the low dose aspirin option in the United States

    Acetylsalicylic acid (ASA)Ticlopidine hydrochlorideClopidogrel bisulfatePrasugrelhydrochlorideTicagrelorTrade NameAspirin1-3Ticlid4Plavix5Effient6Brilinta7ClassSalicylateP2Y12 Receptor AntagonistP2Y12 Receptor AntagonistP2Y12 Receptor AntagonistP2Y12 Receptor AntagonistFormulationActive DrugActive DrugPro-DrugPro-DrugActive DrugMaintenance Dose75-325 mg daily*250 mg BID75 mg daily10 mg daily90 mg BIDReversibleNoNoNoNoYes

  • Membrane PhospholipidsArachadonic AcidProstaglandin H2COX-1Thromboxane A2 Platelet AggregationVasoconstrictionProstacyclin Platelet AggregationVasodilationAspirinAspirin:Mechanism of Action

  • Source: Steering Committee of the Physicians Health Study Research Group. NEJM 1989;321:129-135CI=Confidence interval, CV=CardiovascularAspirin Evidence: Primary PreventionPhysicians Health Study (PHS)22,071 male participants randomized to aspirin (325 mg every other day) followed for an average of 5 years

    Aspirin reduces the risk of myocardial Infarction among men

    End point

    Relative Risk (95% CI)

    P value

    CV Mortality

    0.96 (0.60-1.54)


    Myocardial infarction


    0.34 (0.15-0.75)



    0.59 (0.47-0.74)

  • Source: Ridker P et al. NEJM 2005;352:1293-130439,876 women randomized to aspirin (100 mg every other day) or placebo for an average of 10 years

    Aspirin does not reduce cardiovascular events among womenAspirin Evidence: Primary PreventionWomens Health Study (WHS)

  • BDT, 1988CombinedPPP, 2001HOT, 1998TPT, 1998PHS, 1989RR of MI in Men1. = 0.68 (0.54-0.86) P=0.0011. = 1.13 (0.96-1.33) P=0.15HOT, 1998CombinedWHS, 2005PPP, 20011. BetterPlacebo BetterRR = 0.99 (0.83-1.19) P=0.951. BetterPlacebo BetterRR = 0.81 (0.69-0.96) P=0.01RR of CVA in MenRR of MI in WomenRR of CVA in WomenSource: Ridker P et al. NEJM 2005;352:1293-1304CVA=Cerebrovascular accident, MI=Myocardial infarction, RR=Relative riskAspirin Evidence: Primary Prevention

  • Sex-specific meta-analysis of 51,342 women and 44,114 men randomized to aspirin (doses ranging between 100 mg every other day to 500 mg daily) vs. placebo for 3.7-10 years

    Aspirin reduces the risk of stroke in women and MI in menSource: Berger JS et al. JAMA.2006;295:306-313* p

  • 1,276 asymptomatic patients with DM and an ABI
  • 2,539 diabetic patients without known coronary artery disease randomized to aspirin (81-100 mg) or placebo for a median of 4.7 years

    Aspirin does not reduce the risk of adverse CV events in diabeticsSource: Ogawa H et al. JAMA 2008;300:2134-2141CI=Confidence interval, CV=Cardiovascular, HR=Hazard ratioAspirin Evidence: Primary PreventionJapanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) Study

  • 3,350 patients with an ABI
  • Non-fatal MI Vascular Mortality Major extracranial bleed Serious Vascular Events Antiplatelet BetterAntiplatelet WorseRate Ratios for Vascular Events0P
  • Meta-analysis of 95,456 low risk patients randomized to aspirin (100 mg every other day to 500 mg daily) vs. placebo for 3.7-10 years

    Aspirin reduces the risk of ischemic events, but with a higher rate of bleedingSource: Antithrombotic Trialists Collaboration. Lancet 2009;373:1849-1860Aspirin Evidence: Primary PreventionAntithrombotic Trialists (ATT) Collaboration

    Number of Events (Aspirin vs. Control)Rate ratio (95% CI) (Aspirin vs. Control)Major coronary event934 vs. 11150.82 (0.75-0.90) Non-fatal MI596 vs. 7560.77 (0.69-0.86) CHD mortality372 vs. 3930.95 (0.82-1.10)Stroke655 vs 6820.95 (0.85-1.06) Hemorrhagic116 vs. 891.32 (1.00-1.75) Ischemic317 vs. 3670.86 (0.74-1.00) Unknown cause222 vs. 2260.97 (0.80-1.18)Vascular death619 vs. 6370.97 (0.87-1.09)Any serious vascular event1671 vs. 1883 0.88 (0.82-0.94)Major extracranial bleed335 vs. 2191.54 (1.30-1.82)

  • Source: Antithrombotic Trialists Collaboration. BMJ 2002;324:7186Category % Odds ReductionAcute MIAcute CVA Prior MIPrior CVA/TIAOther high risk CVD (e.g. unstable angina, heart failure) PAD (e.g. intermittent claudication) High risk of embolism (e.g. Afib) Other (e.g. DM)All trials1. Control better Antiplatelet betterEffect of antiplatelet treatment* on vascular events***Aspirin was the predominant antiplatelet agent studied**Include MI, stroke, or deathAspirin Evidence: Secondary Prevention

    Aspirin reduces the risk of adverse cardiovascular events

  • 500-1500 mg 34 19 160-325 mg 19 26 75-150 mg 12 32
  • Aspirin Evidence: Dose and EfficacyClopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events (CURRENT)-OASIS 7 Trial25,087 patients with an ACS randomized in a 2 x 2 factorial trial to double dose clopidogrel (600 mg LD, 150 mg x 7 days, then 75 mg MD) vs. standard dose clopidogrel (300 mg LD and 75 mg MD) and high dose aspirin (300-325 mg) vs. low dose aspirin (75-100 mg)

    Source: CURRENT-OASIS 7 Investigators. NEJM 2010;363:930-942ACS=Acute coronary syndrome, MI=Myocardial infarction, LD=Loading dose, MD=Maintenance doseHR=0.97, P=0.61Higher dose aspirin does not provide benefit in ACS

  • Aspirin (81 mg daily or 100 mg every other day) in at risk women >65 years of ageAspirin in at risk women
  • Aspirin (75-162 mg daily) in [men]* at intermediate risk (10-year risk of CHD >10%)

    Aspirin Recommendations (Continued)Primary PreventionCHD=Coronary heart disease*Specific guideline recommendations for men do not exist, but these guidelines are based on previous general (not gender specific) primary prevention guidelinesSource: Pearson TA et al. Circulation 2002;106:388-391

  • Source: Pignone M et al. Circulation 2010;121:2694-2701ACCF=American College of Cardiology Foundation, ADA=American Diabetes Association, AHA=American Heart Association, CV=Cardiovascular, CVD=Cardiovascular disease, DM=Diabetes mellitus, GI=Gastrointestinal, NSAIDs=Non-steroidal anti-inflammatory drugsIncludes those with family history of premature CVD, hypertension, smoking, dyslipidemia, or albuminuriaLow-dose aspirin therapy (75-162 mg/day) is reasonable for adults with DM and no previous history of vascular disease who are at increased CVD risk (10-year risk >10%) and who are not at increased risk for bleeding (based on a history of previous GI bleeding or peptic ulcer disease or concurrent use of other medications that increase bleeding risk such as NSAIDs or warfarin). Those adults with DM at increased CVD risk include most men >50 years of age or women >60 years of age who have at least one additional major risk factor.**ADA Level CADA/AHA/ACCF Primary Prevention of CV DiseaseAntiplatelet Agent RecommendationsPrimary Prevention

  • ACCF=American College of Cardiology Foundation, ADA=American Di


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