Disclosure. Acute Coronary Syndromes (ACS) Objectives. Pathophysiology. Risk Factors. Update on Treatment of Acute Coronary Syndromes 3/5/2015

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1 Disclosure Update on Treatment of Acute Coronary Syndromes Duchess Domingo, Pharm.D. PGY-1 Pharmacy Practice Resident Broward Health Medical Center I do not have a vested interest in or affiliation with any corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias my presentation 2 Objectives Upon completion of this activity, the participant should be able to: Describe the pathophysiology of Acute Coronary Syndromes (ACS) Classify the disease states that comprise ACS Identify risk factors associated with ACS Recognize brand and generic names of medications used in ACS Explain the mechanism of action, role in therapy, and precautions for all medications used to manage ACS Identify appropriate safety and efficacy monitoring parameters for medications used in ACS Acute Coronary Syndromes (ACS) Spectrum of conditions associated with acute myocardial ischemia and/or infarction Due to reduction in coronary blood flow Unstable Angina (UA) Non-STsegment elevation Myocardial Infarction (NSTEMI) ST-segmentelevation Myocardial Infarction (STEMI) 3 4 Pathophysiology Risk Factors Primary cause atherosclerosis Hallmark of ACS Myocardial Oxygen Supply Myocardial Oxygen Demand Age Gender M > F Family history of coronary artery disease Peripheral arterial disease Diabetes mellitus Tobacco use Renal insufficiency Hypertension Hyperlipidemia Sedentary lifestyle Obesity 5 Acute Coronary Syndrome. American Heart Association

2 Clinical Presentation Diagnosis Chest pain or discomfort Pressure, tightness, fullness Diaphoresis Dyspnea Nausea Abdominal pain Syncope Image: Electrocardiogram (ECG/EKG) Assess for cardiac ischemia or injury ST-depression Transient ST-elevation New T-wave inversion ST-elevation STEMI Anterior ST-depression UA/NSTEMI Cardiac enzymes Troponins, CK-MB, myoglobin May be elevated due to other causes Troponins: most sensitive and specific biomarkers Obtained at presentation, and 3-6 hours after symptom onset Acute Coronary Syndrome. American Heart Association Image: cg-and-ecgss-showing-stemi_and_nstemi.jpg 8 UPDATE: Diagnosis ACS Classification 2007:For patients who present within 6 hours of symptom onset, assessment of early marker (i.e. myoglobin) along with late marker (i.e. troponin) can be considered (Class IIb, Evidence: B) 2014:No benefit for CK-MB assay for diagnosis of MI; reserve use for estimation of infarct size (Class III, Evidence: A) 2007:Re-measure biomarkers in 6-8 hour intervals 2-3 times to measure infarct size (Class IIa, Evidence: B) 2014:Re-measure troponin once on day 3 or 4 in patients with MI as index of infarct size (Class IIb, Evidence: B) UA NSTEMI STEMI Symptoms ECG +/- + +(ST-elevation) Cardiac Enzymes Occlusion Partial Complete NSTE-ACS 9 10 NSTE-ACS 2014 Guidelines: What s New? Early Hospital Care First full revision of recommendations since 2007 Title: UA/NSTEMI NSTE-ACS Initial conservative management Ischemiaguided therapy Stratification of invasive strategy based on timing More emphasis on discharge Medical management recommendations Goals of treatment: immediate relief of ischemia, prevention of MI and death Standard medical therapies Oxygen Nitrates Analgesics β-blockers Calcium channel blockers Cholesterol management Spinler, SA NSTE-ACS clinical practice guidelines what s new?american Heart Association

3 UPDATE: Oxygen Early Hospital Care: Nitrates 2007:Supplemental oxygen should be given to patients with UA/NSTEMI with arterial saturation <90%, respiratory distress, or other high-risk features for hypoxemia (Class I, Evidence: B) 2007:It is reasonable to administer supplemental oxygen to all patients with UA/NSTEMI during first 6 hours after presentation (Class IIa, Evidence: C) Nitrates Relieve ischemic chest pain Vasodilator with peripheral and coronary vascular effects Increases O 2 supply, decreases O 2 demand 2014: Supplemental oxygen should be administered to patients with NSTE- ACS with arterial saturation <90%, respiratory distress, or other high-risk features of hypoxemia (Class I, Evidence: C) Anderson et al ACC/AHA UA/NSTEMI Guideline. Circulation Vol Early Hospital Care: Nitrates Early Hospital Care: Morphine Nitrates Sublingual nitroglycerin: mg every 5 mins for up to 3 doses, assess need for IV nitroglycerin IV nitroglycerin Persistent ischemia Heart failure Hypertension Adverse effects: headache, hypotension Contraindications: use of phosphodiesterase inhibitors within last 24 hrs (sildenafil, vardenafil), 48 hrs (tadalafil), 12 hrs (avanafil) Monitoring: blood pressure, heart rate Morphine Venodilation, reduces myocardial O 2 demand May be beneficial in patients with symptoms despite antianginal treatment 1-5 mg IV during nitroglycerin therapy; may be repeated every 5 to 30 minutes to relieve symptoms Adverse effects: constipation, nausea, vomiting, respiratory depression, hypotension Monitoring: pain control, vital signs, respiratory rate Early Hospital Care: Aspirin Early Hospital Care: β-blockers Aspirin Established 1 st line therapy in NSTE-ACS, reduces incidence of recurrent MI and death Irreversible COX-1 inhibition thromboxane A2 inhibition platelet inhibition Loading dose: mg PO (non-enteric coated) Maintenance dose: mg PO per day May substitute clopidogrelif unable to take aspirin β-blockers Reduces myocardial oxygen demand, improves oxygen supply Decrease HR, contractility, and BP Increases ventricular filling time, coronary artery perfusion Decrease myocardial ischemia, reinfarction, and frequency of complex ventricular dysrhythmias Increases long-term survival

4 Early Hospital Care: β-blockers Early Hospital Care: β-blockers β-blockers Oral therapy should be initiated within first 24 hours Concomitant NSTE-ACS, stabilized HF, reduced systolic function Metoprolol succinate (Toprol XL ) Bisoprolol (Zebeta ) Carvedilol (Coreg ) β-blockers Continue β-blockers in NSTE-ACS patients with concomitant stabilized heart failure and reduced systolic function Contraindications: signs of heart failure, cardiogenic shock, low output state, other contraindications to β-blockade Monitoring: heart rate, blood pressure Early Hospital Care: Calcium Channel Blockers Early Hospital Care: Cholesterol Management Calcium Channel Blockers (CCBs) Decreased heart rate and blood pressure alleviates ischemia Non-dihydropyridines recommended as initial therapy for patients with continuing or frequently recurring ischemia, and have contraindication to β-blockers Negative inotropic, chronotropic, dromotropic effects Diltiazem Verapamil Adverse effects: edema, headache, bradycardia, hypotension Monitoring: blood pressure, heart rate, constipation Cholesterol Management Statin therapy reduces rate of recurrent MI, coronary heart disease mortality, need for revascularization, and stroke pleiotropic effects High-intensity statin should be initiated or continued in all NSTE-ACS with no contraindications Atorvastatin (Lipitor ) 21 Davignon J. Atherosclerosis: evolving vascular biology and clinical implications. Circulation 2004;109: ACE Inhibitors UPDATE: ACE Inhibitors Reduce mortality in patients with recent MI, and LV dysfunction with or without pulmonary congestion Recommendations Initiate and continue indefinitely in all patients with LVEF <0.40, and in those with hypertension, diabetes, or stable CKD, unless contraindicated (Class I, Evidence: A) May substitute angiotensin receptor blocker (ARB) if intolerant to ACEIs 2007:An ACEI administered orally within the first 24 hours can be useful in patients without pulmonary congestion or LVEF <0.40 in the absence of hypotension, or known contraindications (Class IIa, Evidence: B) 2014:ACEI may be reasonable in all other patients with cardiac or other vascular disease (Class IIb, Evidence: B) 23 Anderson et al ACC/AHA UA/NSTEMI Guideline. Circulation Vol

5 Rationale Rationale Danchin et al (2006) Conducted review of randomized controlled trials to assess if long-term ACEI use decreased major cardiovascular events and mortality in patients with CAD and without HF Results: ACEI significantly associated with reductions in all-cause mortality, cardiovascular death, MI and stroke compared with placebo (p<0.001) Sorbets et al (2014) Examined Reduction of Atherothrombosis for Continued Health (REACH) registry of patients with stable CAD without HF for relationship between cardiovascular outcomes and ACEI/ARB use 4 year follow-up risk of CV death, MI, stroke was similar with ACEI/ARB users vs non-users No benefit for ACEI taken with other standard pharmacotherapy in reducing cardiovascular events Danchin N, Cucherat M, Thuillez C, Durand E, Kadri Z, Steg PC. Angiotensin converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction. Arch Intern Med. 2006;166: Sorbets E, Labreuche J, Simon T, Delorme L, Danchin N, Amarenco P, et al. Renin-angiotensin system antagonists and clinical outcomes in stable coronary artery disease without heart failure. Eur Heart J. 2014;35: Other Pharmacotherapy Options Antiplatelet Therapy: P2Y 12 Inhibitors Antiplatelets Aspirin (ASA) P2Y 12 Inhibitors GPIIb/IIIa inhibitors Anticoagulants Unfractionated Heparin (UFH) Enoxaparin (Lovenox ) Fondaparinux (Arixtra ) Bivalirudin (Angiomax ) MOA: Blocks ADP P2Y 12 receptor on platelets Three approved agents Clopidogrel (Plavix ) Ticagrelor (Brilinta ) Prasugrel (Effient ) Recommendations A P2Y 12 inhibitor should be given in addition to aspirin for up to 12 months to all patients with NSTE-ACS without contraindications P2Y 12 Inhibitors: Clopidogrel (Plavix ) P2Y 12 Inhibitors: Ticagrelor (Brilinta ) Loading dose: mg PO Maintenance dose: 75 mg PO daily Adverse effects: bleeding, rash, purpura Contraindications: active bleeding Black Box Warning: diminished effectiveness in poor CYP2C19 metabolizers Monitoring: bleeding, Hgb, Hct Clopidogrelplus aspirin superior to aspirin alone in reducing CV death, and nonfatal MI or stroke Loading dose: 180 mg PO Maintenance dose: 90 mg PO BID Adverse effects: dyspnea (up to 15% of patients within first week of treatment), bradycardia Contraindications: active bleeding, history of intracranial hemorrhage, severe hepatic impairment Monitoring: bleeding, Hgb, Hct, signs/symptoms of dyspnea Must be given with ASA (<100 mg/day)

6 P2Y 12 Inhibitors: Prasugrel (Effient ) Only indicated in PCI Adverse effects: bleeding, hypertension, nausea, hyperlipidemia, headache Contraindications: active bleeding, prior TIA or stroke Black Box Warning: bleeding risk Not recommended in patients >75 years old except in high-risk situations Do not start in patients who will undergo CABG Use with caution in patients <60 kg and concomitant use of medications that increase bleeding risk Manage bleeding without discontinuing if possible Monitoring: Hgb, Hct, platelets 31 UPDATE: Antiplatelet Therapy 2012 Focused Update: For UA/NSTEMI patients in whom initial conservative strategy is selected, clopidogrel or ticagrelor should be added to aspirin and anticoagulant therapy as soon as possible after admission and administered for up to 12 months (Class I, Evidence: B) 2012 Focused Update: Patients for whom an initial invasive strategy is selected, antiplatelet therapy in addition to aspirin should be initiated with one of the following: Before PCI Clopidogrel (Class I, Evidence: B), ticagrelor (Class I, Evidence: B), an IV GPIIb/IIIa inhibitor (Class I, Evidence: B) At time of PCI Clopidogrel (Class I, Evidence: A), prasugrel (Class I, Evidence: B), ticagrelor (Class I, Evidence: B), IV GPIIb/IIIa inhibitor (Class I, Evidence: A) Jneid et al ACCF/AHA UA/NSTEMI Focused Update. Circulation Vol UPDATE: Antiplatelet Therapy 2014: It is reasonable to use ticagrelor in preference to clopidogrel for P2Y 12 treatment in patients with NSTE-ACS who undergo an early invasive or ischemia-guided strategy (Class IIa, Evidence: B) 2014: It is reasonable to choose ticagrelorover clopidogrelin patients treated with an early invasive strategy and/or coronary stenting (Class IIa, Evidence: B) 2014: It is reasonable to choose prasugrelover clopidogrelin patients who undergo PCI who are not at high risk of bleeding complications (Class IIa, Evidence: B) Rationale Ticagrelor vs. clopidogrel (PLATO) Multicenter, double-blind, randomized trial Ticagrelor group Lower composite outcomes of death from vascular causes, MI, or stroke Mortality benefit greater No difference in major, life-threatening, fatal or CABG-related bleeding; increase in non-cabg related bleeding with ticagrelor Benefit over clopidogrel limited to patients taking mg aspirin Ticagrelor Black Box Warning Bleeding risk Maintenance doses of aspirin >100 mg/day reduces efficacy of ticagrelor avoid 33 Wallentin L, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11): Rationale Rationale Aug Analysis of subgroup data from NSTE- ACS patients from PLATO (Lindholm et al) Evaluated efficacy and safety of ticagrelor vs. clopidogrel in NSTE-ACS subgroup of PLATO trial Benefits of ticagrelor consistent with main study findings Clopidogrel vs. Prasugrel (TRITON-TIMI 38) Multi-center, double-blind, controlled trial Prasugrel group Less CV mortality, non-fatal MI, non-fatal stroke More non-cabg related major bleeding, and CABGrelated major bleeding No difference in CV mortality Lindholm D, Varenhort C, Cannon CP, Harrington RA, Himmelmann A, Maya J, et al. Ticagrelor vs. clopidogrel in patients with non-st-segment elevation acute coronary syndrome with or without revascularization: results from the PLATO trial. Eur Heart J. 2014;35: Wiviott ST, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):

7 Antiplatelet Therapy: GPIIb/IIIa Inhibitors Anticoagulant Therapy: UFH MOA: Blocks GPIIb/IIIa receptors on platelet surface prevents fibrinogen cross-linking of platelets Options Tirofiban (Aggrastat ) Eptifibatide (Integrilin ) Abciximab (ReoPro ) for patients undergoing PCI Recommendations Consider use in patients with NSTE-ACS receiving DAPT with intermediate/high risk as part of initial antiplatelet therapy MOA: Potentiates action of anti-thrombin III inactivates thrombin and coagulation factors and plasmin prevents conversion of fibrinogen to fibrin Loading dose: 60 IU/kg; max 4000 IU Initial infusion: 12 IU/kg/hr; max 1000 IU/hr Adverse effects: thrombocytopenia, bleeding Contraindications: hypersensitivity, severe thrombocytopenia, active bleeding Monitoring: bleeding, Hgb, Hct, aptt, platelets Continue for 48 hours or until PCI Anticoagulant Therapy: Enoxaparin (Lovenox ) Anticoagulant Therapy: Bivalirudin (Angiomax ) MOA: Same as UFH (Factor X to II ratio 3:1) Dose: 1 mg/kg SQ q12h Renal dose adjustment CrCl <30 ml/min: 1 mg/kg SQ daily Adverse effects: bleeding Monitoring: platelets, renal function, bleeding Should be continued for the duration of hospitalization or until PCI is performed MOA: Direct thrombin inhibitor Loading dose: 0.10 mg/kg IV Maintenance dose (for early invasive strategy): 0.25 mg/kg/hr IV Adverse effects: bleeding, hypotension, nausea, pain Contraindications: active major bleeding Monitoring: aptt Continue until diagnostic angiography or PCI Anticoagulant Therapy: Fondaparinux (Arixtra ) MOA: Selective factor Xa inhibitor Dose: 2.5 mg SQ daily Contraindications: CrCl<30 ml/min, <50 kg (prophylaxis), active bleeding Adverse effects: bleeding Monitoring: CBC, platelets, renal function, bleeding Continue for duration of hospitalization or until PCI is performed If PCI is performed during therapy, administer additional anticoagulant (UFH or bivalirudin) 41 NSTE-ACS Treatment Overview 42 7

8 General Principles of Treatment Invasive strategy Triages patients to invasive diagnostic evaluation Ischemic-guided strategy Invasive evaluation if: Fail medical therapy Objective evidence of ischemia Clinical indicators of very high prognostic risk (i.e. high TIMI or GRACE scores) Patients with refractory ischemic symptoms or hemodynamic instability urgent coronary angiography and revascularization Both strategies initially utilize dual anti-platelet therapy (DAPT) and anti-coagulation therapy Amsterdam et al AHA/ACC NSTE-ACS Guideline. JACC Vol 64, No NSTE-ACS Treatment UPDATE: Ischemia-Guided Therapy NSTE-ACS Previously known as initial conservative management in 2007 guidelines Ischemia-guided therapy more clearly conveys physiologic rationale of the approach Emphasis on medical therapy Ischemia- Guided Strategy Early Invasive Strategy 45 Spinler, SA NSTE-ACS clinical practice guidelines what s new?. American Heart Association 46 Ischemia-Guided Strategy Seeks to avoid routine early use of invasive procedures Initiation of medical management then risk stratification Recommended for initially stabilized patients without serious comorbidities and at elevated risk for clinical events Advantages Some patients will stabilize during medical therapy Can potentially avoid costly and unnecessary invasive procedures 47 NSTE-ACS Treatment Ischemia-Guided Initiate DAPT and Anticoagulant Therapy Therapy Effective PCI with stenting Therapy Ineffective CABG Late Hospital/Posthospital Care 48 8

9 NSTE-ACS Treatment Ischemia- Guided Strategy NSTE-ACS Early Invasive Strategy 49 Early Invasive Strategy Seeks to rapidly risk stratify patients by assessing coronary anatomy Diagnostic angiography with possible revascularization Recommended for patients with refractory angina or hemodynamic or electrical instability 2014: Stratified by timing Immediate (within 2 hours) Early (within 24 hours) Delayed (within hours) Advantages Rapid and definitive evaluation Earlier revascularization in appropriate patients May facilitate earlier discharge 50 Invasive Strategy Early Invasive Strategy Strategy Immediate Invasive (within 2 hours) Early Invasive (within 24 hours) Delayed Invasive (within hours) Indications Refractory angina Signs/symptoms of HF or new or worsening mitral regurgitation Hemodynamic instability Recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapy Sustained VT or VF GRACE score >140, change in troponin New ST depression Diabetes or renal insufficiency Reduced LV dysfunction (EF <0.40) Early post-infarction angina PCI within 6 months Prior CABG GRACE risk score ; TIMI 2 51 Not recommended in: Extensive comorbidities Acute chest pain and low likelihood of ACS who are troponin negative 52 NSTE-ACS Treatment Early Invasive Initiate DAPT and Anticoagulant Therapy Consider GPI in addition to ASA and P2Y12 inhibitor in high-risk patients Medical therapy chosen based on cath findings Therapy effective Therapy ineffective Antiplatelet Therapy in PCI and CABG Aspirin Can reduce operative morbidity and mortality If already on ASA, should take 81 mg to 325 mg non-enteric coated before PCI or CABG If not on ASA, should be given 325 mg non-enteric coated ASA before PCI Continue indefinitely after PCI PCI with stenting CABG Late Hospital/Post-hospital care

10 Antiplatelet Therapy in PCI and CABG Antiplatelet Therapy in PCI and CABG P2Y 12 inhibitors Loading dose given before PCI with stenting Clopidogrel 600 mg Prasugrel 60 mg Ticagrelor 180 mg Should be given for at least 12 months in patients receiving stent Clopidogrel 75 mg daily Prasugrel 10 mg daily Ticagrelor 90 mg BID Discontinue clopidogreland ticagrelor at least 5 days before elective CABG and at least 24 hours before urgent CABG Discontinue prasugrel for at least 7 days before elective CABG GPIIb/IIIa Inhibitors Reduces incidence of composite ischemic events in patients undergoing PCI Consider in patients with NSTE-ACS and high-risk features not adequately pre-treated with clopidogrel or ticagrelor, or in patients treated with UFH and pretreated with clopidogrel Discontinue eptifibatide or tirofiban at least 2-4 hours and abciximab at least 12 hours before CABG Anticoagulation Therapy in PCI Anticoagulation Therapy in PCI Reduces risk of intracoronary and catheter thrombus formation Discontinue after PCI if no compelling reason to continue therapy UFH Bivalirudin Can use as monotherapy over UFH and GP IIb/IIIa inhibitor combination if high-risk for bleeding Enoxaparin Administer additional 0.3 mg/kg IV at time of PCI to patients who receive <2 doses or if last dose was 8-12 hours before PCI Anticoagulation Therapy in PCI Fondaparinux Increased risk of catheter thrombosis avoid as monotherapy in PCI patients If PCI is performed during fondaparinux therapy, give additional 85 IU/kg of UFH immediately before PCI UPDATE: Post-Discharge Care

11 Post-Discharge Care Medical Regimen and Use of Medications at Discharge Goals for continued medical therapy:potential prognostic benefits, control of ischemic symptoms, treatment of major risk factors Selection of regimen should be individualized ABCDE A aspirin, antianginals, ACE inhibitors B beta-blockers, blood pressure C cholesterol, cigarettes D diet, diabetes mellitus E education, exercise Continue medications to control ischemia after discharge in patients who: Do not undergo coronary revascularization, Incomplete or unsuccessful revascularization Recurrent symptoms All patients should be given sublingual or spray nitroglycerin Inform patients about symptoms of worsening myocardial ischemia and MI and how to seek emergency care If angina worsens or changes, patients should contact their clinicians immediately Patients should be educated about modification of CV risk factors Post-Discharge Care Post-Discharge Care Antiplatelet Therapy ASA continued indefinitely P2Y 12 inhibitors continued up to 12 months in all patients without contraindications treated with ischemia-guided strategy Stents at least 12 months (if risk > benefits, can discontinue therapy) Consider DAPT >12 months in patients undergoing stent implantation (Class IIb, Evidence: C) Anticoagulant Therapy Duration of triple antithrombotic therapy (vitamin K antagonist, aspirin, P2Y 12 inhibitor) should be minimized to limit risk of bleeding Targeting lower INR may be reasonable in patients with NSTE-ACS managed with aspirin and a P2Y 12 inhibitor Post-Discharge Care Post-Discharge Care Proton Pump Inhibitors Decrease risk of GI bleeding in patients on DAPT with history of GI bleed or at increased risk for bleeding Should be given to NSTE-ACS patients with history of GI bleed who require triple antithrombotic therapy (vitamin K antagonist, ASA, P2Y 12 inhibitor) (Class I, Evidence: C) Reasonable use in patients without known history of GI bleed who require triple antithrombotic therapy (Class IIa, Evidence: C) Can potentially diminish efficacy of clopidogrel avoid concomitant use Risk Reduction Strategies Lifestyle changes Risk factor education Medical therapy Revascularization Patient Education Recommendations Cholesterol management Tobacco cessation Blood pressure management Lifestyle management

12 Post-Discharge Care Vaccinations Pneumococcal pneumonia 65 years of age All high risk patients with cardiovascular disease Influenza All patients with cardiovascular disease 67 Amsterdam et al AHA/ACC NSTE-ACS Guideline. JACC Vol 64, No Assessment Questions References All acute coronary syndromes present with positive cardiac enzymes FALSE ACE-Inhibitors should be started and continued indefinitely in all patients with LVEF <0.40 and in those with hypertension, diabetes, or stable chronic kidney disease unless contraindicated TRUE For all patients with ACS, P2Y12 inhibitors should be continued for 6 months FALSE Amsterdam EA, Wenger NK, Brindis RG et al AHA/ACC Guideline for the management of patients with non-st-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;DOI: /j.acc Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 Guidelines for the management of patients with unstable angina/non-stelevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2007;116:e148-e304 Jneid H, Anderson J, Wright RS, et al ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-st-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2012;126: Acute Coronary Syndrome. American Heart Association. Available at Accessed Dec Spinler, SA NSTE-ACS clinical practice guidelines what s new?. American Heart Association. Available at New_UCM_466977_Article.jsp. Accessed on Feb Available at: Accessed Jan Davignon J. Atherosclerosis: evolving vascular biology and clinical implications. Circulation 2004;109:39-43 Danchin N, Cucherat M, Thuillez C, Durand E, Kadri Z, Steg PC. Angiotensin converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction. Arch Intern Med. 2006;166: For patients receiving concurrent ticagrelor and aspirin therapy, aspirin doses should be limited to less than 100 mg daily TRUE 69 Sorbets E, Labreuche J, Simon T, Delorme L, Danchin N, Amarenco P, et al. Renin-angiotensin system antagonists and clinical outcomes in stable coronary artery disease without heart failure. Eur Heart J. 2014;35: Wallentin L, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11): Lindholm D, Varenhort C, Cannon CP, Harrington RA, Himmelmann A, Maya J, et al. Ticagrelor vs. clopidogrel in patients with non-stsegment elevation acute coronary syndrome with or without revascularization: results from the PLATO trial. Eur Heart J. 2014;35: Wiviott ST, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):