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Guidelines Applied to Practice (GAP) American College of Cardiology, Puerto Rico Chapter GAP Acute Coronary Syndrome American College of Cardiology Puerto Rico Chapter San Juan Intercontinental; December 12: José R. Rivera del Río MD Casa del Médico, Mayaguez; December 13: Anibal Lugo MD Casa del Médico, Ponce; December 14: José Gómez Rivera MD GAP Management of Patient With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction ACC/AHA Guidelines AHA/ACC Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2006 Update Gregg C. Fonarow, MD and Sidney Smith Jr, MD on behalf of the Secondary Prevention Writing Group TABLE OF CONTENTS GAP I. Introduction Purpose Organization Overview of the ACS II. Initial evaluation and management Clinical Assessment Early Risk Stratification Immediate Management III. Hospital care IV. Coronary revascularization V. Hospital discharge VI. Special Groups Purpose GAP Major cause of ED visit and hospitalization – 1997: 5,315,000 ED visits for CP Increased morbidity: – Mortality in hospital: 2- 8% – Recurrent MI in first year: 20% – Recurrent AP in first year has a mortality of 43% Exposition to various physician other than cardiologists These guidelines were made for the medical personnel managing these conditions with the intention of decreasing the related morbidity ACC GAP in Michigan: Reliability Science and Mortality Benefit Kim A. Eagle, MD On behalf of the ACC GAP Steering Committee, the Michigan GAP Collaborators, and Partners 383 Cardiologists 33 Hospitals 30 Businesses 20 Health Plans 10 Health Systems 60 Nurse Project Leaders 45 Physician Champions GAP Key Elements Patient ACC Tool Kit • • • • • Patients Providers Hospitals Health Coalitions MPRO Standing Orders Critical Pathways Patient Information Patient Discharge Contract Hospital Data Key Care Priorities Nurse Doctor AMI GAP Collaborative Model (12 month time frame) Participants (19 teams) Prework Develop Grand Framework Rounds & Changes November 2001 Oversight Team P Jan-Mar 2002 A Phone Conference 12/6/01 LS 1 Workshop Planning A S LS 2 March Implementation P P D D A S D S LS 3 LS 4 April May Monitoring tool use Remeasurement LS 5 November Results & Debriefing Supports Email Visits Monthly Team Reports Phone calls Assessments 12/12/01 *© 2001 Institute for Healthcare Improvement, Modified by Cecelia Montoye, RN, MSN, CPHQ GAP IN MICHIGAN Comparison of the Medicare diagnosis code 410.xx from patient treated the year before the GAP implementation. Records were copied and forwarded to DynKePRO’ Centers for CMS Clinical Data Abstraction Center. Comparison pre GAP and post GAP were done Lesson V: QI Saves Lives! Medicare Patients with AMI before and after GAP JACC 2005 40 35 30 25 Before After 20 15 10 5 0 Hosp Mort 30d Mort RRR 24% P< 0.017 23% 0.001 1 yr Mort 13% 0.004 Eagle KA et al. JACC 2005;46:1242-48. Applying Classification of Recommendations and Level of Evidence Class I Class IIa Class IIb Class III Benefit >>> Risk Benefit >> Risk Additional studies with focused objectives needed Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Risk ≥ Benefit No additional studies needed Procedure or treatment SHOULD be performed or administered IT IS REASONABLE to perform procedure or administer treatment Procedure or treatment MAY BE CONSIDERED Level A Multiple (3-5) population risk strata evaluated (Multiple RCT’s) General consistency of direction and magnitude of effect Level B Procedure or treatment should NOT be performed or administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Limited (2-3) population risk strata evaluated (Limited RCT’s) Level C Very limited (1-2) population risk strata evaluated (General consensus) DEFINITION GAP UNSTABLE ANGINA (UA) One of the Acute Coronary Syndromes (ACS) Presents an AP lasting more than 20 minutes Without S-T elevation in the EKG Without cardiac enzymes elevation Expressed as: – a. New onset – b. At rest – c. Progressing effort angina – d. Post myocardial Infarction (MI) – e. After a revascularization process. DEFINITION GAP NSTEMI is expressed similar to UA but elevation of cardiac enzymes is present. Usually ends as NQMI. Less frequently as QwMI. STEMI has the same clinical picture as a NSTEMI but presents S-T elevations in the EKG. Usually ends as QwMI and less frequently as NQMI. Hamm Lancet 358:1533,2001 Presentation Ischemic Discomfort Working Dx Acute Coronary Syndrome Davies MJ Heart 83:361, 2000 ECG No ST Elevation NSTEMI Biochem. Marker Final Dx Unstable Angina ST Elevation 25% 10% Myocardial Infarction NQMI Qw MI PATHOGENESIS GAP Coronary artery narrowing caused by non occluding thrombus on a disrupted atherosclerotic plaque. Microembolization explains the release of the markers. (Most frequent) Dynamic obstruction (spasm, Prinzmetal) Severe narrowing Arterial inflammation Secondary UA (Increased demand) GAP The Matrix Skeleton of Unstable Coronary Artery Plaque Fissures in the fibrous cap TM Davies MJ. Circulation. 1996;94:2013-2020. © 1999 Professional Postgraduate Services® TABLE OF CONTENTS GAP I. Introduction Purpose Organization Overview of the ACS II. Initial evaluation and management Clinical Assessment Early Risk Stratification Immediate Management III. Hospital care IV. Coronary revascularization V. Hospital discharge VI. Special Groups Clinical Assessment GAP Class I – 1. Patients with possible ACS should not be evaluated by telephone but referred to a facility that allows evaluation by a physician and record an ECG. (C) – 2. Patients with suspected ACS with chest discomfort at rest over 20 minutes, hemodynamic instability or recent syncope or presyncope should be referred to an ED or a CPC. (C) Early Risk Stratification GAP Class I – 1. Patients with chest discomfort should undergo risk stratification focused on anginal Sx., physical findings, ECG findings and biomarkers of cardiac injury. (C) – 2. A 12 lead ECG should be done immediately (in 10 min.) in ACS patients. (C) – 3. Cardiac injury biomarkers should be done in patients with ACS. Preferred Troponins. Other options CK-MB. If in 6 hours no elevation need at least another sample in 6-12 hours frame. (C) Likelihood of CAD with increased Risk of Death or Non Fatal MI HIGH MODERATE LOW ONE PRESENT: NO “HIGH”; MUST HAVE: NO “HIGH”, “MOD.”; MUST HAVE: HX HX: MI, CAD, SD, age M >60, F > 70 Constant AP>20min; Accelerated IHD Sx last 48 hrs AP prolonged >20min, rest, resolved w/NTG Increased AP(Freq, severity, duration, or at lower threshold) PE PE (w/IHD), new MR, S3, new rales, hypotension, age > 75 y/o Age > 70 years GAP ECG MARKERS AP,rest,ST >.05 mm, T T inversions > .2 mv inversions > .2 mv Pathological Q wave LBBB, sustained VT Elevation of TnI, TnT or CK-MB No elevations Unchanged ECG or normal ECG No elevations Search for non-coronary CP causes GAP Class I Level C GAP PAINLESS MI Old age Females Diabetes Post coronary by pass surgery Up to 33% in the National Registry of MI {NRMI}-2 Study GAP Elderly: Atypical presentation Dyspnea 44% Chest pain 33-60% Sweating 14-23% Syncope 18% Confusion 8% GAP GAP Troponins for Evaluation and Management of ACS Advantages Risk Stratificaton Sens/Spec > CKMB Detect Recent MI Selection of Rx Detect Reperfusion Disadvantages Low sens. early (< 6h) Repeat at 8-12 h if neg. Limited ability to detect late minor reinfarction Recommendation Useful as single test to efficiently Dx NSTEMI Clinicians should familiarize themselves with Dx “cutoffs” in local lab and other non CAD causes of its elevation Increase in CK-MB GAP IHD Cardioversion Miopericarditis PCI Fast tachycardia Hypothyroidism Small GI RF Dystrophies Neuromuscular diseases Rhabdomyolisis Tongue Uterus Diaphragm Bladder Malignancy Increase in Troponins GAP IHD Cardioversion Pulmonary embolism Tachycardia Decompensated heart failure Ablation Pericarditis Sepsis Myocardial trauma or inflammation Cold agglutinins Aortic dissection Immediate Management GAP Class I (see annexed chart) – The Hx, PE, ECG and markers must be integrated to assign patient in categories. (C) – The patient with definitive or possible ACS must be evaluated and observed in a special unit and repeated ECG and markers after 6-12 hrs of Sx repeated. (B) – In suspected or present ACS with ECG and markers non DX, a stress test (exercise or pharmacological) should be performed in the ED or as outpatient basis shortly after DH. (C) Immediate Management GAP Class I (continued) – Patient with definitive ACS, positive ECG or markers, positive stress test or hemodynamic instability must be admitted to hospital for further management. (C) – Patients with possible ACS and negative markers unable to exercise should have a pharmacological stress test. (B) – Patients with S-T elevations and ACS must be evaluated for urgent reperfusion therapy. (A) Symptoms suggestive of ACS Rapid Triage Obtain Biomarkers Non Cardiac Diagnosis As Per Other Dx Assess 12 lead ECG Chronic Stable Angina Medical Rx Goal = 10 min Possible ACS Definite ACS ASA Antithrombin Beta Blocker ACS Protocol Symptoms Suggestive of ACS Possible ACS Definite ACS No ST elev. Non dx ECG Neg. card. markers Observe f/u studies Neg Neg Outpt f/u Stress ST-Tw changes Ongoing pain Positive card markers Hemodynamic abnl. ST elev. Evaluate for reperfusion Pos Pos Dx of ACS confirmed Admit to hospital Acute ischemia pathway TABLE OF CONTENTS GAP I. Introduction Purpose Organization Overview of the ACS II. Initial evaluation and management Clinical Assessment Early Risk Stratification Immediate Management III. Hospital care IV. Coronary revascularization V. Hospital discharge VI. Special Groups = Controversial issue General Anti-Ischemic Therapy GAP Class I – Bed rest and ECG monitoring. (C) – NTG, sublingual or spray, followed by IV Nitroglycerin for AP and relief of associated symptoms. (C) – Supplemental oxygen for cyanosis or respiratory distress; finger pulse oximetry or ABG to confirm adequate O2 saturation (>90%) and continue oxygen in hypoxemic presence. (C) General Anti-Ischemic Therapy GAP Class I (continued) – Morphine sulfate IV when AP can’t be controlled with NTG or pulmonary congestion present. (C) – Beta blocker therapy 2002 (IV first dose if ongoing chest pain and no contraindications) followed by oral administration. (B) Now (2004) its preferred oral MX (I) and IV left for the pt with tachycardia or HTN. (IIa) – In patients with ongoing AP and contraindications for BB, diltiazem or verapamil can be used in absence of contraindications or HF. (B) – ACEI when BP have not be controlled after NTG and BB and when patient in CHF or in ACS and DM. (B) General Anti-Ischemic Therapy GAP Class IIa – Oral long acting calcium antagonists for recurrent ischemia in the absence of contraindications and when BB and NTG fully used. (C) – An ACEI in all patients with ACS. (B) – Intra-aortic balloon counterpulsation for severe ischemia that is continuous or recurrent or for hemodynamic instability before or after coronary angiography. (C) GAP Antiplatelets and anticoagulant therapy Antiplatelets Therapy GAP Class I – Give chewable ASA ASAP (If not allergic). Initial dose of 162 - 325 mgr. Continue indefinitely. (IA) – Where no intervention is planned add clopidogrel to ASA immediately and continue it for one month (IA) at least or up to 9 months (IB). Aspirin Evidence: Dose and Efficacy Indirect Comparisons of Aspirin Doses on Vascular Events in High-Risk Patients Aspirin Dose No. of Trials (%) 500-1500 mg 34 19 160-325 mg 19 26 75-150 mg 12 32 <75 mg 3 13 Any aspirin 65 23 0 Odds Ratio for Vascular Events P<.0001 0.5 Antiplatelet Better Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86 1.0 1.5 2.0 Antiplatelet Worse GAP CLOPIDOGREL Efficacy of Clopidogrel or Ticlopidine in Reducing Coronary Events After Stenting 30-Day Major Adverse Cardiac Events Trial CLASSICS TOPPS Müller CCF Lenox Hill Mayo N. Memorial S. Illinois Wash. Hosp. Wessex Overall Odds Ratio & 95% CI N Clopid. (%) Ticl. (%) 1020 1016 700 2369 2565 2827 1.3 2.6 3.1 5.7 2.4 0.6 0.9 3.5 1.7 8.9 3.8 1.6 1378 875 844 -361 13,955 0.8 2.1 2.0 3.4 2.0 2.2 1.4 0.5 5.2 3.9 OR=.73, P=.003 0.1 Clopidogrel Better 1 Ticlopidine Better 10 CLASSICS, Clopidogrel Aspirin Stent Intervention Coopoerative Study. Bhatt DL, et al. J Am Coll Cardiol. 2002;39:9-14. (Copyright 2002, with permission from American College of Cardiology Foundation) CURE: Primary End Point MI/Stroke/CV Death Cumulative Hazard Rate 0.14 Placebo + Aspirin 0.12 0.10 0.08 Clopidogrel + Aspirin 0.06 20% RRR P=.00009† (N=12,562) 0.04 0.02 0.00 0 3 6 9 Follow-up (mo) 12 CURE, Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events; MI, myocardial infarction; CV, cardiovascular; RRR, relative risk reduction. † Plavix® [package insert]; 2002. Adapted with permission (2002) from the Massachusetts Medical Society. Yusuf S, et al. N Engl J Med. 2001;345:494-502. CREDO: Benefits of Clopidogrel Plus Aspirin to 1 Year Following PCI CV Death, MI or Stroke Combined Endpoint Occurrence (%) 15 Placebo* Clopidogrel* 11.5% 27% RRR 10 8.5% P=.02 5 0 0 3 6 9 12 Months From Randomization * Plus ASA and other standard therapies . Steinhubl S, et al. JAMA. 2002;288:2411-2420. (Copyright 2002 American Medical Association. All rights reserved) GAP CLOPIDOGREL INITIAL DOSE Clopidogrel GAP If surgery is contemplated hold clopidogrel for 5-7 days. In patients in whom PCI is planned add clopidogrel and continue for at least for one month at least (IA) or 9 months if no risk of bleeding (IB) GAP Anticoagulant Therapy Anticoagulant Therapy GAP Anticoagulation with subcutaneous LMWH (Enoxaparin preferred, if no surgery within 24 hours: IIA) or unfractionated heparin (UFH) should be added to antiplatelets therapy with ASA and / or clopidogrel (IA) Unstable Angina Anti-coagulant Therapy GAP • Heparin – recommendation is based on documented efficacy in many trials of moderate size – meta-analyses (1,2) of six trials showed a 33% risk reduction in MI and death, but with a two fold increase in major bleeding – titrate PTT to 2x the upper limits of normal 1. Circulation 1994;89:81-88 2. JAMA 1996;276:811-815 DATA FROM ESSENCE • 54% of Heparin patients were still outside the therapeutic range 12 to < 24 hours after drug administration • At 24 to < 48 hrs 48.7% of these patients were still outside the therapeutic range D/MI/Urg Revasc (%) TIMI Risk Score For UA/NSTEMI 50 40 • • • • • • • Age > 65 y > 3 CAD Risk Factors Prior Stenosis > 50 % ST deviation > 2 Anginal events < 24 h ASA in last 7 days Elev Cardiac Markers UFH ENOX 40.9 30 20 10 28.8 26.2 4.7 3.5 13.214.1 19.9 14.9 3 4 20 8.3 8.6 0 0/1 2 5 6/7 Number of Risk Factors Antman et al JAMA 284 : 835, 2000 GAP GP IIb/IIIa BLOCKERS GP IIb/IIIa Blockers GAP A platelet GP IIb/IIIa antagonist should be administered, in addition to ASA and heparin, to patients in whom catheterization and PCI are planned. The GP IIb/IIIa antagonist may also be administered just prior to PCI (IA). GP IIb/IIIa Blockers GAP Use of eptifibatide or tirofiban should be considered, in addition to ASA, LMWH or UFH, in patients with; persistent ischemia, Troponins elevation, or any other high risk features in which invasive management is not planned (IIA). GP IIb/IIIa Inhibitor During Medical Management and After PCI: CAPTURE, PURSUIT, PRISM-PLUS Post PCI Medical Rx 10% N=12,296 P=.001 Control GP IIb/IIIa inhibitor Death or MI 8% N=2754 P=.001 8.0% 6% 4.9% 4.3% 4% 2.9% 2% 0% 0 +24 h +48 h +72 h +24 h +48 h PCI Boersma E, et al. Circulation. 1999;100:2045-2048. (with permission from Lippincott Williams & Wilkins, www.lww.com) Meta-analysis of IIb/IIIa Inhibition in PCI for 30-Day Mortality IIb/IIIa Inhibitor Better Placebo Better N Ctrl Trt EPIC EPILOG RAPPORT CAPTURE Impact I Impact II Restore Epistent Espirit ISAR 2 Admiral Cadillac 2099 2792 483 1265 150 4010 2141 2399 2064 401 300 2082 1.7 0.7 2.1 1.3 2.0 1.1 0.7 0.6 0.6 4.5 6.6 2.3 1.5 0.4 2.5 1.0 1.0 0.7 0.8 0.5 0.4 2.0 3.4 1.9 Combined 0.73 (0.55,0.96) 20186 1.3 0.9 P=.024 0.1 1 10 OR Kong DF, et al. Am J Cardiol. 2003;92:651-655. (Copyright 2003, with permission from Excerpta Medica, Inc.) GAP Unstable Angina Anti-platelet Therapy • Summary – the four “P trials” (PRISM, PRISM-PLUS, PARAGON, PURSUIT) – all show reduction of death rate between 1.3% and 3.4% - in addition to the benefit of aspirin – useful in the management of patients with unstable angina and MI without ST elevation GAP GP IIb/IIIa blockers recommended when; •Recurrent ischemia, despite meds •Elevated Troponins I or T •New ST-segment depression •New CHF symptoms •High-risk stress test findings •LV dysfunction (EF <40%) •Hemodynamic instability, sustained VT ACC/AHA Class I Recommendations for Antithrombotic Therapy* Possible ACS Likely/Definite ACS Aspirin Aspirin + SQ LMWH* or IV Heparin Clopidogrel Definite ACS With Invasive Strategy (Catheterization/PCI) or High Risk (IIa)* Aspirin + IV Heparin + IV Platelet GP IIb/IIIa Antagonist Clopidogrel * Class IIa: enoxaparin preferred over UFH unless CABG planned within 24 hours. ACC, American College of Cardiology; AHA, American Heart association; ACS, acute coronary syndrome; PCI, percutaneous coronary intervention; SQLMWH, subcutaneous low molecular-weight heparin; IV, intravenous. Braunwald E, et al. J Am Coll Cardiol. 2000;36:970-1062. Co adjuvant therapy GAP not recommended Insulin and glucose – DIGAMI and UKPDS: strict blood sugar control decreased the mortality and incidence of MI – GIPS: 30 days decreased mortality was seen in the Killip class I patients using the insulin-glucosepotassium infusion – Some consider the infusion in patients with IHDAMI and increased glucose levels – BUT! In CREATE-ECLA JAMA 2005, Jan: “There is no benefit to the addition of high dose glucose-insulin-potassium infusion in patients with ST segment elevation MI.” (20,201 patients) Co adjuvant therapy GAP not recommended Lidocaine prophylactically Magnesium IV HRT ACC/AHA Guideline Summary Risk Stratification post UA/NSTEMI I IIa IIb III C GXT for pts. w/o IHD/CHF symptoms /12- 24 hours @ C GXT at intermediate risk Asx after 2-3 days @ B Patients with low level capacity, limited motion, COPD or @, do a pharmacological GXT B Angiography if instability or Sx persists C ECHO or MUGA for LV function if not scheduled for angiography @: Decide the GXT mode depending in the ECG S-T changes, digoxin effect, LBBB, delta wave and PPM presence. Also depends on patient ability to perform the test and the local expertise. Braunwald E et al. J Am Coll Cardiol. 2002;40:1366-1474. TABLE OF CONTENTS GAP I. Introduction Purpose Organization Overview of the ACS II. Initial evaluation and management Clinical Assessment Early Risk Stratification Immediate Management III. Hospital care IV. Coronary revascularization V. Hospital discharge VI. Special Groups Invasive vs Conservative Strategy for UA/NSTEMI VANQWISH 2003 RITA-3 MATE VINO TIMI IIIB TRUCS Mortality p=0.001 N-F MI p=0.012 Re. hosp. p<0.0001 Conservative No. of Patients: 920 ISARCOOL TACTICSTIMI 18 FRISC II Invasive 1674 7018 UA, unstable angina, NSTEMI, non–ST-segment myocardial infarction; ISAR, Intracoronary Stenting and Antithrombic Regimen Trial; RITA, Randomized Intervention Treatment of Angina; VANQWISH, Veterans Affairs Non-QWave Infarction Strategies in Hospital study; MATE, Medicine vs Angioplasty for Thrombolytic Exclusions trial; TACTICS-TIMI18, Treat Angina with Aggrestat® and Determine Cost of Therpay with Invasive or Conservative Strategy; FRISC, Fragmin during InStability in Coronary artery disease. ACC/AHA Guideline Summary Early Conservative and/or Invasive Strategies I IIa IIb III Early invasive strategy in high-risk patients with any of the following: • • • • • • • • A Recurrent ischemia, despite meds Elevated troponin I or T New ST-segment depression New CHF symptoms High-risk stress test findings LV dysfunction (EF <40%) Hemodynamic instability, sustained VT Prior CABG, PCI within 6 months Either strategy in low- to moderate-risk patients without contraindications to revascularization B C Early invasive strategy for pts with repeated ACS and without high-risk features or ongoing ischemia EF=ejection fraction. Braunwald E et al. J Am Coll Cardiol. 2002;40:1366-1474. ACC/AHA Guideline Summary CABG in patients post UA/NSTEMI I IIa IIb III A Significant LM disease A Three vessel disease and EF < 50% A Two vessel, LAD prox., w LVEF< 50 or ischemia in test C Repeat CABG for X’s SVG stenosis (Esp. LAD) B CABG w LIMA in MVD pts and RX DM Braunwald E et al. J Am Coll Cardiol. 2002;40:1366-1474. ACC/AHA Guideline Summary PCI in patients post UA/NSTEMI I IIa IIb III A Pts. w MVD w suitable CAD and NL EF / w/o DM A IV GP IIb/IIIa in PCI C Focal SVG or multiple stenosis not for CABG B 2-3 vessel CAD w LAD prox. / DM or dec. LVEF with anatomy accessible for PCI Braunwald E et al. J Am Coll Cardiol. 2002;40:1366-1474. ACC/AHA Guideline Summary PCI or CABG in patients post UA/NSTEMI I IIa IIb III B B B 1-2 vessel CAD w/o LAD prox. but w large ischemic territory at risk 1-2 vessel CAD w/o LAD prox. but w moderate ischemic territory at risk 1 vessel disease with significant proximal LAD Braunwald E et al. J Am Coll Cardiol. 2002;40:1366-1474. TABLE OF CONTENTS GAP I. Introduction Purpose Organization Overview of the ACS II. Initial evaluation and management Clinical Assessment Early Risk Stratification Immediate Management III. Hospital care IV. Coronary revascularization V. Hospital discharge VI. Special Groups AHA/ACC Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2006 Update Gregg C. Fonarow, MD and Sidney Smith Jr, MD on behalf of the Secondary Prevention Writing Group Cigarette Smoking Recommendations Goal: Complete Cessation and No Exposure to Environmental Tobacco Smoke •Ask about tobacco use status at every visit. •Advise every tobacco user to quit. •Assess the tobacco user’s willingness to quit. I IIa IIb III •Assist by counseling and developing a plan for quitting. •Arrange follow-up, referral to special programs, or pharmacotherapy (including nicotine replacement and bupropion. •Urge avoidance of exposure to environmental tobacco smoke at work and home. Blood Pressure Control Recommendations Goal: <140/90 mm Hg or <130/80 if diabetes or chronic kidney disease I IIa IIb III I IIa IIb III Blood pressure 120/80 mm Hg or greater: Initiate or maintain lifestyle modification: weight control, increased physical activity, alcohol moderation, sodium reduction, and increased consumption of fresh fruits vegetables and low fat dairy products Blood pressure 140/90 mm Hg or greater (or 130/80 or greater for chronic kidney disease or diabetes) As tolerated, add blood pressure medication, treating initially with beta blockers and/or ACE inhibitors with addition of other drugs such as thiazides as needed to achieve goal blood pressure Lipid Management Goal I IIa IIb III LDL-C should be less than 100 mg/dL I IIa IIb III Further reduction to LDL-C to < 70 mg/dL is reasonable If TG >200 mg/dL, non-HDL-C should be < 130 mg/dL* *Non-HDL-C = total cholesterol minus HDL-C Lipid Management Goals: NCEP Risk Category High risk: CHD or CHD risk equivalents (10-year risk >20%) and Very high risk: ACS or established CHD plus: multiple major risk factors (especially diabetes) or severe and poorly controlled risk factors Consider Drug Therapy LDL-C and non-HDLC Goal Initiate TLC <100 mg/dL if TG > 200 mg/dL, non-HDL-C should be < 130 mg/dL 100 mg/dL >100 mg/dL (<100 mg/dL: consider drug options) <70 mg/dL, non-HDL-C < 100 mg/dL All patients >100 mg/dL (<100 mg/dL: consider drug options) ATP=Adult Treatment Panel, CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol, TLC=Therapeutic lifestyle changes Grundy, S. et al. Circulation 2004;110:227-39. Lipid Management Recommendations Assess fasting lipid profile in all patients, and within 24 hours of hospitalization for those with an acute event. For patients hospitalized, initiate lipid-lowering medication as recommended below prior to discharge according to the following schedule: I IIa IIb III If baseline LDL-C > 100 mg/dL, initiate LDL-lowering drug therapy I IIa IIb III I IIa IIb III If on-treatment LDL-C > 100 mg/dL, intensify LDLlowering drug therapy (may require LDL lowering drug combination) If baseline is LDL-C 70 to 100 mg/dL, it is reasonable to treat to LDL < 70 mg/dL When LDL lowering medications are used, obtain at least a 30-40% reduction in LDL-C levels. Lipid Management Recommendations I IIa IIb III If TG are 200-499 mg/dL, non-HDL-C should be < 130 mg/dL I IIa IIb III Further reduction of non-HDL to < 100 mg/dL is reasonable I IIa IIb III Therapeutic options to reduce non-HDL-C: More intense LDL-C lowering therapy I (B) or Niacin (after LDL-C lowering therapy) IIa (B) or Fibrate (after LDL-C lowering therapy) IIa (B) If TG are > 500 mg/dL, therapeutic options to prevent pancreatitis are fibrate or niacin before LDL lowering therapy; and treat LDL-C to goal after TG-lowering therapy. Achieve non-HDL-C < 130 mg/dL, if possible HMG-CoA Reductase Inhibitor: Secondary Prevention Relationship between LDL Levels and Event Rates in Secondary Prevention Trials of Patients with Stable CHD Statin 30 4S Placebo Event (%) 25 4S 20 LIPID 15 LIPID CARE 10 HPS 5 0 CARE HPS TNT (atorvastatin 10 mg/d) TNT (atorvastatin 80 mg/d) 0 70 90 110 130 150 LDL-C (mg/dL) 170 190 210 LDL-C=Low density lipoprotein cholesterol; TNT=Treating to New Targets; HPS=Heart Protection Study; CARE=Cholesterol and Recurrent Events Trial; LIPID=Long-term Intervention with Pravastatin in Ischaemic Disease; 4S=Scandinavian Simvastatin Survival Study. LaRosa JC et al. NEJM. 2005;352:1425-1435 HMG-CoA Reductase Inhibitor: Secondary Prevention Heart Protection Study (HPS) 20,536 patients with CAD, other occlusive arterial disease, or DM randomized to simvastatin (40 mg) or placebo for 5.5 years Event Rate Ratio (95% CI) Baseline LDL-C (mg/dL) Statin (n = 10,269) Placebo (n = 10,267) <100 282 (16.4%) 358 (21.0%) 100–129 668 (18.9%) 871 (24.7%) 130 1083 (21.6%) 1356 (26.9%) All patients 2033 (19.8%) 2585 (25.2%) Statin Better Statin Worse 0.76 (0.72–0.81) P<0.0001 0.4 CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus, HPS Collaborative Group. Lancet 2002;360:7-22 0.6 0.8 1.0 1.2 1.4 Physical Activity Recommendations I IIa IIb III Goal: 30 minutes 7 days/week, minimum 5 days/week Assess risk with a physical activity history and/or an exercise test, to guide prescription I IIa IIb III Encourage 30 to 60 minutes of moderate intensity aerobic activity such as brisk walking, on most, preferably all, days of the week, supplemented by an increase in daily lifestyle activities I IIa IIb III Advise medically supervised programs for high-risk patients (e.g. recent acute coronary syndrome or revascularization, HF) Weight Management Recommendations I IIa IIb III Goal: BMI 18.5 to 24.9 kg/m2 Waist Circumference: Men: < 40 inches Women: < 35 inches Assess BMI and/or waist circumference on each visit and consistently encourage weight maintenance/ reduction through an appropriate balance of physical activity, caloric intake, and formal behavioral programs when indicated. I IIa IIb III I IIa IIb III If waist circumference (measured at the iliac crest) >35 inches in women and >40 inches in men initiate lifestyle changes and consider treatment strategies for metabolic syndrome as indicated. The initial goal of weight loss therapy should be to reduce body weight by approximately 10 percent from baseline. With success, further weight loss can be attempted if indicated. *BMI is calculated as the weight in kilograms divided by the body surface area in meters2. Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2. CV Risk Increases with Body Mass Index Hazard Ratio Hemorrhagic Stroke Ischemic Stroke Ischemic Heart Disease 4.0 4.0 4.0 2.0 2.0 2.0 1.0 1.0 1.0 0.5 0.5 0.5 16 20 24 28 32 36 CV=Cardiovascular 16 20 24 28 32 36 Body Mass Index (kg/m2)* Body mass index is calculated as the weight in kilograms divided by the body surface area in meters2. Mhurchu N et al. Int J Epidemiol 2004;33:751-758 16 20 24 28 32 36 Diabetes Mellitus Recommendations Goal: Hb A1c < 7% I IIa IIb III Lifestyle and pharmacotherapy to achieve near normal HbA1C (<7%). I IIa IIb III Vigorous modification of other risk factors (e.g., physical activity, weight management, blood pressure control, and cholesterol management as recommended). I IIa IIb III Coordinate diabetic care with patient’s primary care physician or endocrinologist. ) HbA1c = Glycosylated hemoglobin Antiplatelet Agents / Anticoagulation Recommendations Aspirin Recommendations I IIa IIb III I IIa IIb III I IIa IIb III Start and continue indefinitely aspirin 75 to 162 mg/d in all patients unless contraindicated For patients undergoing CABG, aspirin (100 to 325 mg/d) should be started within 48 hours after surgery to reduce saphenous vein graft closure Post-PCI-stented patients should receive 325 mg per day of aspirin for 1 month for bare metal stent, 3 months for sirolimus-eluting stent and 6 months for paclitaxel-eluting stent Clopidogrel Recommendations Start and continue clopidogrel 75 mg/d in combination with aspirin I IIa IIb III for post ACS or post PCI with stent placement patients for up to 12 months for post PCI-stented patients >1 month for bare metal stent, >3 months for sirolimus-eluting stent >6 months for paclitaxel-eluting stent *Clopidogrel is generally given preference over Ticlopidine because of a superior safety profile Clopidogrel use post-PCI + stent: Mortality n = 1501 drug-eluting stent (DES), n = 3165 bare-metal stent (BMS) 6 4 Cumulative incidence (%) 2 0 12 DES + CL DES – CL BMS + CL BMS – CL CL = clopidogrel 252 276 346 1644 18 Months 237 258 339 1627 24 230 244 331 1596 Eisenstein EL et al. JAMA. 2006;297. 4666 pts: 3156 BMS and 1501 DES. Duke Heart Center 2000-2006 Clopidogrel use post-PCI + stent: Composite of death or MI 6 4 Cumulative incidence (%) 2 0 12 DES + CL DES – CL BMS + CL BMS – CL 252 276 346 1644 18 Months 237 256 336 1621 24 230 240 327 1582 Eisenstein EL et al. JAMA. 2006;297. 4666 pts: 3156 BMS and 1501 DES. Duke Heart Center 2000-2006 Renin-Angiotensin-Aldosterone System Blockers Recommendations ACE Inhibitor Recommendations I IIa IIb III Use in all patients with LVEF < 40%, and those with diabetes or chronic kidney disease indefinitely, unless contraindicated I IIa IIb III Consider for all other patients ACE=Angiotensin converting enzyme, LVEF= left ventricular ejection fraction ACE Inhibitor Evidence: Post MI with LVD or HF AIRE SAVE Radionuclide EF 40% Probability of Event TRACE Clinical and/or radiographic signs of HF Echocardiogram EF 35% 0.4 0.35 Placebo 0.3 ACE-I 0.25 0.2 0.1 0.15 OR: 0.74 (0.66–0.83) 0.05 0 0 1 2 3 4 Years ACE-I=Angiotensin converting enzyme inhibitors, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio Flather MD, et al. Lancet. 2000;355:1575–1581 ACE Inhibitor Evidence: CAD, CVD, PVD or DM Heart Outcomes Prevention and Evaluation (HOPE) Study CV death, MI, or stroke (%) 9,297 patients with DM or vascular disease plus one additional CV risk factor, but without HF or known LVSD randomized to ramipril (10 mg) or placebo for 5 years 0.20 Ramipril 0.15 Placebo 0.10 0.05 22% RRR, P<0.001 0.00 0 500 1000 1500 Days of Follow-Up ACE-I=Angiotensin converting enzyme inhibitors, DM=Diabetes mellitus, CV=Cardiovascular, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction HOPE Investigators. NEJM 2000;342:145-153 Angiotensin Receptor Blocker Recommendations I IIa IIb III Use in patients who are intolerant of ACE inhibitors with HF or post MI with LVEF less than or equal to 40%. I IIa IIb III Consider in other patients who are ACE inhibitor intolerant. I IIa IIb III Consider use in combination with ACE inhibitors in systolic dysfunction HF. ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction, HF=Heart failure, MI=Myocardial infarction ARB Evidence: Post MI with LVD or HF Valsartan in Acute Myocardial Infarction Trial (VALIANT) All Cause Mortality 14,703 patients with post-MI HF or LVSD (EF <0.40) randomized to captopril (50 mg three times daily), valsartan (160 mg twice daily), or captopril (50 mg three times daily) plus valsartan (80 mg twice daily) over 2 years 0.4 Captopril 0.3 Valsartan Valsartan and Captopril 0.2 0.1 Valsartan vs. Captopril: HR = 1.00; P = 0.982 Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726 0.0 0 6 12 18 24 30 Months EF=Ejection fraction, HR=Hazard ratio, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, RAS=Renin angiotensin system Pfeffer M et al. NEJM 2003;349:1893-1906. 36 Aldosterone Antagonist Recommendations I IIa IIb III Use in post MI patients, without significant renal dysfunction or hyperkalemia, who are already receiving therapeutic doses of an ACE inhibitor and beta blocker, have an LVEF < 40% and either diabetes or heart failure *Contraindications include abnormal renal function (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) and hyperkalemia (K+ >5.0 meq/L) ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction, MI=Myocardial infarction Aldosterone Antagonist: Post MI HF and LVSD Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) All Cause Mortality (%) 6,644 patients with evidence of heart failure and LVSD (EF <0.40) after a MI randomized to eplerenone (50 mg) or placebo for 16 months Eplerenone Placebo 25 20 15 10 5 0 RR = 0.85, P=0.008 0 6 12 18 Month EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction Pitt B et al. NEJM 2003;348:1309-21 24 30 36 b-blocker Recommendations b-blocker Recommendations I IIa IIb III Start and continue indefinitely in all post MI, ACS, LV dysfunction with or without HF symptoms, unless contraindicated. I IIa IIb III Consider chronic therapy for all other patients with coronary or other vascular disease or diabetes unless contraindicated. *Precautions but still indicated include mild to moderate asthma or chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds. MI=Myocardial infarction, HF=Heart Failure b-blocker Evidence Summary of Secondary Prevention Trials of b-blocker Therapy Total # Patients RR (95% CI) Acute treatment 28,970 0.87 (0.77-0.98) Secondary prevention 24,298 0.77 (0.70-0.84) Overall 53,268 0.81 (0.75-0.87) Phase of Treatment 0.5 CI=Confidence interval, RR=Relative risk 1.0 RR of death b-blocker Placebo better better 2.0 Antman E, Braunwald E. Acute Myocardial Infarction. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A textbook of Cardiovascular Medicine, 6th ed., Philadelphia, PA: W.B. Sanders, 2001, 1168. b-blocker Evidence: Post MI with Left Ventricular Dysfunction Proportion Event-free Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN) 6,644 patients with LVEF <0.40 after a MI with or without HF randomized to carvedilol or placebo for 24 months 1 0.95 n=975 0.9 Carvedilol n=984 0.85 0.8 0.75 0.7 RR 0.77 P=.03 0 0.5 1 1.5 Years The CAPRICORN Investigators. Lancet. 2001;357:1385–1390. Placebo 2 2.5 Influenza Vaccination I IIa IIb III Patients with cardiovascular disease should have influenza vaccination TABLE OF CONTENTS GAP I. Introduction Purpose Organization Overview of the ACS II. Initial evaluation and management Clinical Assessment Early Risk Stratification Immediate Management III. Hospital care IV. Coronary revascularization V. Hospital discharge VI. Special Groups GAP Women – should be managed similar as men (IB) Elderly – Consider health, comorbidities, cognitive status and life expectancy (IC) – Attention to pharmacokinetics and hypotensive drugs (IB) – Intensive therapy welcomed under close observation (IB) Diabetes Mellitus – Is an independent risk factors (IA) – CABG for MVD with LIMA (IB) GAP Variant AP – Angiography to S-T elevations corrected by nitrates or calcium blockers (IB) – Patients with normal or non obstructive anatomy use nitrates and /or Calcium blockers (IB) – Provocative testing with non obstructing CAD (IIB) Syndrome X – Risk factors reduction (IC) – Medical therapy with BB, Ca blockers and nitrates (IB) GAP POST CABG – Same management as pre CABG patients (IC) Lower threshold for diagnostic catheterization – Imaging stress test better (IC) – Repeat CABG for multiple lesions in the SVG (IIC) – PCI for focal SVG stenosis (IIC) GAP Cocaine related CAD – NTG and calcium blockers for S-T depression/elevation (IC) – Angiography in AP not resolving with nitroglycerine or calcium blockers. Add lytics or PCI if needed (IC) “I am convinced that we will save more lives from cardiovascular disorders over the next 10 years by CONSISTENT USE of knowledge we already have than by all the NEW ADVANCES we discover…” Kim Eagle, 2004 GAP Management of Patient With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction ACC/AHA Guidelines Guidelines Applied to Practice (GAP) American College of Cardiology, Puerto Rico Chapter JACC September 6, 2005:906-19 Clopidogrel Loading Dose Clopidogrel Loading Dose GAP 1. J Am Coll Cardiol September 5, 2006;48:931-8 In NSTE ACS clopidogrel more than 300 mgr (even 900 mgr) provided faster onset of action, and greater reductions in platelet activation during the first 24 hours. 2. J Am Coll Cardiol October 3, 2006;48:1339-45 In NSTE ACS 600 mgr loading of clopidogrel shows benefit in platelet reactivity and clinical prognosis. “A treatment gap between therapy that is dictated by evidence-based medicine and therapy that occurs in practice is not a deficit of knowledge; rather, it is a deficit of implementation.” Sidney Smith, MD Chief Scientific Officer American Heart Association Use of Cardiac Markers in ACS GAP URL = 99th %tile of Reference Control Group Multiples of the URL 50 20 Cardiac troponin after “classical” AMI (can last 10-14 days) CK-MB after AMI 10 5 Cardiac troponin after “microinfarction” 2 Upper reference limit 1 0 1 2 3 4 5 6 Days After Onset of AMI Modified from: ESC/ACC Comm “MI redefined…” JACC 36: 959,2000 7 8 Wu AH et al. Clin Chem 1999;45:1104. Components of Secondary Prevention Cigarette smoking cessation Blood pressure control Lipid management to goal Physical activity Weight management to goal Diabetes management to goal Antiplatelet agents / anticoagulants Renin angiotensin aldosterone system blockers Beta blockers Influenza vaccination JNC VII Lifestyle Modifications for BP Control Modification Recommendation Approximate SBP Reduction Range Maintain normal body weight (BMI=18.524.9) 5-20 mmHg/10 kg weight lost Diet rich in fruits, vegetables, low fat dairy and reduced in fat 8-14 mmHg Restrict sodium intake <2.4 grams of sodium per day 2-8 mmHg Physical activity Regular aerobic exercise for at least 30 minutes on most days of the week 4-9 mmHg Moderate alcohol consumption <2 drinks/day for men and <1 drink/day for women 2-4 mmHg Weight reduction Adopt DASH eating plan BMI=Body mass index, SBP=Systolic blood pressure Chobanian AV et al. JAMA. 2003;289:2560-2572 Exercise Evidence: Mortality Risk Observational study of self-reported physical activity in 772 men with established coronary heart disease Light or moderate exercise is associated with lower risk Wannamethee SG et al. Circulation 2000;102:1358-1363 Metabolic Syndrome: Risk of Developing DM Diabetes Prevention Program (DPP) Incidence of DM (%) 3,234 patients with elevated fasting and post-load glucose levels randomized to placebo, metformin (850 mg twice daily), or lifestyle modification* for 2.8 years Placebo Metformin Lifestyle modification 40 20 0 1 2 3 4 Lifestyle modification reduces the risk of developing DM *Includes 7% weight loss and at least 150 minutes of physical activity per week Knowler WC et al. NEJM 2002;346:393-403 Clopidogrel Evidence: ACS (Non-STEMI and UA) Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial Rate of death, myocardial infarction, or stroke 12,562 patients with a NSTEMI-ACS randomized to daily aspirin (75-325 mg) or clopidogrel (300 mg load, 75 mg thereafter) plus aspirin (75-325 mg) for 3-12 months (average 9 months) 0.14 Aspirin + Clopidogrel Aspirin + Placebo 0.12 0.10 0.08 0.06 0.04 0.02 P<0.001 0.00 0 3 6 Months of Follow Up NSTEMI-ACS=Non ST-segment elevation acute coronary syndrome The CURE Trial Investigators. NEJM. 2001;345:494-502 9 12 Clopidogrel Evidence: Post PCI Clopidogrel for the Reduction of Events during Observation (CREDO) Trial Risk of MI, Stroke, or Death (%) 2,116 patients undergoing PCI randomized to 4 weeks of DAP* followed by aspirin (75-325 mg) monotherapy vs persistent DAP* for 1 year 15 4 weeks of DAP 1 year of DAP 10 5 27% RRR, P=0.02 00 3 6 Months from Randomization 9 DAP=Dual antiplatelet therapy, PCI=Percutaneous coronary intervention, RRR=Relative risk reduction *Dual antiplatelet therapy=Aspirin (75-325 mg daily) plus Clopidogrel (300 mg load followed by 75 mg daily). Steinhubl S et al. JAMA 2002; 288:2411-20 12 b-blocker Evidence: Benefit in HF and LVSD Study Drug HF Severity Patients (n) Follow-up (years) Mean Dosage Effects on Outcomes CIBIS Bisoprolol* ModerateSevere 641 1.9 3.8 mg/day All cause mortality 22% (p=NS) CIBIS-II Bisoprolol* ModerateSevere 2,647 1.3 7.5 mg/day All cause mortality 34% (P<0.0001) BEST Bucindolol* ModerateSevere 2,708 2.0 152 mg/day All cause mortality 10% (p=NS) MERIT-HF Metoprolol succinate# MildModerate 3,991 1.0 159 mg/day All cause mortality 34% (P=0.0062) MDC Metprolol tartrate* MildModerate 383 1.0 108 mg/day Death or Need for Tx 30% (P=NS) CAPRICORN Carvedilol Mild 1,989 1.3 40 mg/day All cause mortality 23% (P =0.03) US Carvedilol Carvedilol MildModerate 1,094 0.5 45 mg/day All-cause mortality† 65% (P=.0001) COPERNICUS Carvedilol Severe 2,289 0.9 37 mg/day All-cause mortality 35% (P =0.0014) *Not an approved indication †Not a planned end point. #Not approved for severe HF or mortality reduction alone Lesson I: Use of Tools Drives Improvement 100 80 85 94*** 90*** 91*** 87* 81*** 82 Percent 71 73 76* 93*** 92*** 91*** 86*** 85** 84 87*** 81 78* 77 74*** 73 72 73 68*** 68 60 51 40 20 0 ASA Pre Post Post with tools BB LDL Chol ASA BB ACE Smoking Chol Counseling Rx Dietary Counseling *p ≤ 0.05 **p ≤ 0.01 ***p ≤ 0.01 Eagle KA, et al. The Guidelines Applied in Practice (GAP) Initiative to Improve MI Care in Michigan - Lessons Learned from 3 Projects in 33 Hospitals. JACC 41:2003 Modified from Libby P Circ 104:365,2001 Superficial Erosion GAP Acute Coronary Syndrome Ruptured Fibrous Cap HMG-CoA Reductase Inhibitor: Secondary Prevention Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)—TIMI 22 Study 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months Recurrent MI or Cardiac Death 30 Atorvastatin Pravastatin 25 16% RRR 20 15 10 5 P =0.005 0 3 6 9 12 15 18 21 24 27 30 Follow-up (months) ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction Cannon CP et al. NEJM 2004;350:1495-1504 Anticoagulation Recommendations I IIa IIb III Manage warfarin to international normalized ratio 2.0 to 3.0 for paroxysmal or chronic atrial fibrillation or flutter, and in post-MI patients when clinically indicated (e.g., atrial fibrillation, LV thrombus.) I IIa IIb III Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with increased risk of bleeding and should be monitored closely ACE Inhibitor Evidence: CAD European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) 13,655 patients with CAD and presumed normal left ventricular function randomized to perindopril (8 mg) or placebo for 4.2 years Cardiovascular death (0.86; 0.72-1.03) Non-fatal MI (0.78; 0.20-0.90) Cardiac arrest (0.54; 0.20-1.47) Combined endpoint (0.80; 0.71-0.91) 0 0.5 Favors Perindopril 1 1.5 2 Favors Placebo ACE-I=Angiotensin converting enzyme inhibitors, CAD=Coronary artery disease, CV=Cardiovascular, MI=Myocardial infarction EUROPA Investigators. Lancet 2003;362:782-788 ACE Inhibitor Evidence: CAD Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial 8,290 patients with stable coronary artery disease and normal left ventricular function randomized to trandolapril (4 mg) or placebo for 4.8 years Primary End Point (%)* 30 Placebo Trandolapril 25 20 15 10 5 0 0 1 2 3 4 5 6 Years After Randomization *Includes death from cardiovascular causes, myocardial infarction, or coronary revascularization PEACE Trial Investigators. NEJM 2004;351:2058-2068 ARB Evidence: Heart Failure Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Added Trial 2,548 patients with symptomatic HF and LVSD (EF <40%) randomized to candesartan (32 mg) or placebo in addition to an ACE-I over 34 months CV Death of Hospitalization for HF 50 Placebo 40 Candesartan 30 20 10 HR 0.85, p=0.011 0 0 1 2 Years 3 3.5 ACE-I=Angiotensin converting enzyme inhibitors, ARB=Angiotensin receptor blockers, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, RAS=Renin angiotensin system McMurray JJ et al. Lancet. 2003;362:767-71 ARB Evidence: Heart Failure Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Alternative Trial 2,028 patients with symptomatic HF, LVSD (EF <40%), and intolerance to ACE-I randomized to candesartan (32 mg) or placebo over 34 months CV Death of Hospitalization for HF 50 Placebo 40 Candesartan 30 20 10 HR 0.77 p=0.0004 0 0 1 2 Years 3 ACE-I=Angiotensin converting enzyme inhibitors, ARB=Angiotensin receptor blockers, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction Granger CB et al. Lancet. 2003;362:772-777 Aldosterone Antagonist: Heart Failure Randomized Aldactone Evaluation Study (RALES) 1,663 patients with NYHA Class III or IV HF and LVSD (EF <0.35) randomized to spironolactone (25 mg) or placebo (50 mg) for 24 months Survival (%) 1.00 Spironolactone Placebo .90 .80 .70 .60 .50 RR = 0.70, P<0.001 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NYHA=New York Heart Association Pitt B et al. NEJM 1999;341:709-717 Secondary Prevention Conclusions • Evidence confirms that aggressive comprehensive risk factor management improves survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life for these patients. • Every effort should be made to ensure that patients are treated with evidence-based, guideline recommended, life-prolonging therapies in the absence of contraindications or intolerance. Likelihood of having CAD HIGH RISK MOD RISK LOW RISK GAP ANY OF: NO “HIGH”, ANY OF: NO “HIGH”, “MOD.”, ANY OF: Definitive AP:M<60, F<70 or Probable AP;M>60, F>70 CP, not AP HX Hx: MI, SD, CAD, Classical AP, AP: M>60, F>70 Variant AP PE(w/IHD), new MR, S3, new rales, hypotension Extracardiac vascular disease, Male, DM Chest pain reproduced by palpation New STE >.05 mv; T inv. >.2 mv, W/ sX Fixed Q waves; Abn.new ST/Twaves Normal ECG T flat or inv Elevation of TnI, TnT (>.1) or CK-MB No elevations No elevations PE ECG MARKERS Aspirin Evidence: Secondary Prevention Effect of antiplatelet therapy* on vascular events** Category % Odds Reduction Acute myocardial infarction Acute stroke Prior myocardial infarction Prior stroke/transient ischemic attack Other high risk Coronary artery disease (e.g. unstable angina, heart failure) Peripheral arterial disease (e.g. intermittent claudication) High risk of embolism (e.g. atrial fibrillation) Other (e.g. diabetes mellitus) All trials *Aspirin was the predominant antiplatelet agent studied **Vascular events include MI, stroke, or death Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86. 0.0 0.5 1.0 1.5 2.0 Antiplatelet better Control better Enoxaparin preferred (IIa) If no surgery in 24 hours (IIa) Use eptifibatide or tirofiban should be considered, in addition to ASA, LMWH or UFH; in patients with persistent ischemia, Ti elevations or any Other high risk feature, in which invasive Mx is not planned.