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National Clinical Guidelines: An Update in Coronary Artery DiseaseJune 19, 2011

Joseph P. Bryant, Pharm.D., BCPSLCDR, U.S. Public Health ServiceIndian Health Service 1ObjectivesReview Updated Guidelines for the Management of Coronary Artery Disease (CAD)ACC/AHA STEMI and NSTEMI GuidelinesReview Key Drug Interactions Impacting CADProton Pump Inhibitors (PPIs) & ClopidogrelReview important FDA guidance Impacting CADDrug Safety Communication Simvastatin 80mg

2Background Information3Importance of Managing Heart DiseaseCardiovascular (CV) disease is the leading cause of hospitalizations in the U.S. at ~ 6.2 million discharges per yearIs a major contributor to morbidity, morality & healthcare costEach year there are more than 1.3 million myocardial infarctions (MIs)An estimated 2200 Americans die from CV diseases per dayIn 2010, the cost of Heart Disease in the U.S. was ~ $316.4 billion44STEMI vs. NSTEMIClassification:STEMI ST segment elevation MIST segmented elevated on ECGNSTEMI Non-ST segment elevation MIST segment not elevated, but rather may see ST segment depression, T-wave inversion or no change on ECGSTEMIAre at the greatest risk of death and reinfarctionInitiate reperfusion therapy as soon as possibleNSTEMIInitiate therapy based upon risk stratification

55Risk Stratification in NSTEMIThrombosis in Myocardial Infarction (TIMI) Risk ScoreBased upon clinical presentation & medical history

Medical Presentation:ST-segment depression (0.5mm or greater)Two or more episodes of chest discomfort with past 24 hoursPositive biochemical markers (troponin I or T)

6Risk Stratification in NSTEMIPatient History:Age 65 years or olderThree or more of the following risk factors for CAD:HypercholesterolemiaHypertensionDiabetes MellitusSmokingFamily history of premature CHDKnown CAD (50% or greater stenosis of a coronary artery)Use of aspirin with the past 7 days

7Risk Stratification in NSTEMIScore Assessment:1 point is assigned for each of the 4 medical history & clinical presentation factorsTotal number of points are calculated together which assigns the patients risk for the composite end point of death, MI or urgent need for revascularization within 14 daysHigh risk: 5-7 pointsMedium risk: 3-4 pointsLow risk: 0-2 points

88Levels of RecommendationsClass I: Evidence and/or general agreement that procedure or treatment is useful & effectiveClass II: Evidence is conflicting and/or there is divergence of opinion regarding the usefulness or efficacy of the procedure or treatment Class IIa: Recommendations and the weight of evidence or opinion is in favor of the procedure or treatmentClass IIb: Recommendations and the weight of evidence are less established be evidence or opinionClass III: Recommendation that the treatment or procedure should not be completed Either not useful or may be harmful9ObjectivesReview Updated Guidelines for the Management of Coronary Artery Disease (CAD)ACC/AHA STEMI and NSTEMI GuidelinesReview Key Drug Interactions Impacting CADProton Pump Inhibitors (PPIs) & ClopidogrelReview important FDA guidance Impacting CADDrug Safety Communication Simvastatin 80mg

10STEMI Treatment Algorithm1111NSTEMI Treatment Algorithm1212NSTEMI Treatment Algorithm1313Therapeutic Treatment Options14Platelet ActivationPlatelets adhere to the vascular injuryADP is released from the plateletADP binds to P2Y12 receptors helping activate plateletsActivated platelets expose glycoprotein IIb/IIIaExposed GPIIb/IIIa crosslink with fibrin to form platelet aggregatesAggregates embolize and cause obstructions leading to myocardial ischemia and infarction.

15Clotting Cascade

1616Aspirin TherapyMOA: Thromboxane A2 InhibitorRecommendation: Class I STEMI or NSTEMIContraindications:Hypersensitivity, active bleed or severe risk for bleedingDosing & Duration of Therapy:Day 1 (regardless of therapy): 160-325mgNon-PCI: 75-162mg on day 2 and continue definitelyPCI: Based upon type of stentBare metal: 162-325mg for 30 days; then 75-162mg daily Sirolimus-eluting: 162-325mg for 3 months; then 75-162mg dailyPaclitaxel-eluting: 16 -325mg for 6 months; then 75-162mg dailyContinue therapy indefinitely

17Thienopyridine AntiplateletsMOA:Irreversibly bind to P2Y12 class of ADP receptors, which prevents GPIIb/IIIa receptor complex and thus reducing platelet aggregationEffect is for the life of the platelet ~ 7-10 daysFDA Approved Products:Ticlopidine (Ticlid)Clopidogrel (Plavix)Prasugrel (Effient)

1818Clopidogrel (Plavix)Contraindications:Hypersensitivity, active bleeding or severe bleeding riskWarnings:Diminished antiplatelet effect due to impaired CYP2C19 functionGeneral risk of bleedingPatients with recent TIA or strokeThrombotic thrombocytopenic purpuraConsider potential PPI interactionRecommendations: Class ISTEMI & NSTEMI (with or without PCI) with aspirinPatients with aspirin hypersensitivityDiscontinue 5 days before elective CABG surgery

1919Clopidogrel (Plavix)Dosing:STEMI Patients receiving fibrinolytic or no reperfusion300mg on Day 1; followed by 75mg dailyPatients receiving PCI:300-600mg on Day 1; followed by 75mg dailyNSTEMI: PCI or Non-PCI:300-600mg on Day 1, followed by 75mg dailyDuration of Therapy:Continue for minimum of 12 months (Class I) and up to 15 months if necessary (Class IIb)Continue indefinitely in patients with aspirin allergy

20Prasugrel (Effient)Contraindications:Hypersensitivity, active bleeding, prior stroke/TIAWarnings:General risk of bleedingAge >75*CABG or other surgical procedureBody weight 60kg: 60mg day 1, then 10mg dailyPatients