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THE ABC’S OF THE AHA/ACC Ischemic Heart Disease GUIDELINES Roger S. Blumenthal, MD Professor of Medicine

THE ABC’S OF THE AHA/ACC Ischemic Heart Disease GUIDELINES Roger S. Blumenthal, MD Professor of Medicine Director, The Johns Hopkins Ciccarone Center For The Prevention of Heart Disease. DEFINITION.

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THE ABC’S OF THE AHA/ACC Ischemic Heart Disease GUIDELINES Roger S. Blumenthal, MD Professor of Medicine

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  1. THE ABC’S OF THE AHA/ACC Ischemic Heart Disease GUIDELINES Roger S. Blumenthal, MD Professor of Medicine Director, The Johns Hopkins Ciccarone Center For The Prevention of Heart Disease

  2. DEFINITION PRIMARY Prevention: Modification of risk factors or prevent their development to prevent or delay the onset of CHD. SECONDARY Prevention: Initiation of Rx to reduce recurrent CHD events in patients with CHD. PRIMARY AND A HALFPrevention*: As individuals with subclinical CHD are identified, the distinction between primary and secondary prevention becomes blurred. CHD=Coronary heart disease *Celermajer DS. JACC 2005;45:1994-6

  3. ASPIRIN RECOMMENDATIONS SECONDARY PREVENTION Aspirin (75-325 mg daily) in those with known CHD or carotid artery or leg artery narrowings due to plaque. Aspirin (100-325 mg daily) in those that have undergone CABG surgery*. CABG=Coronary artery bypass graft, CHD=Coronary heart disease *To be administered within the first 48 hours after surgery in order to reduce the risk of saphenous vein graft failure. Doses >162 mg/day may be continued for up to one year.

  4. CLOPIDOGREL EVIDENCE: SECONDARY PREVENTION CLOPIDOGREL IN UNSTABLE ANGINA TO PREVENT RECURRENT EVENTS (CURE) TRIAL 12,562 patients with a NSTE-ACS randomized to daily aspirin (75-325 mg) or clopidogrel (300 mg load, 75 mg thereafter) plus aspirin for 9 months ASPIRIN + CLOPIDOGREL ASPIRIN + PLACEBO RATE OF DEATH, MYOCARDIAL INFARCTION, OR STROKE P<0.001 0 3 6 9 12 MONTHS OF FOLLOW UP DAP=Dual antiplatelet therapy, NSTE-ACS=Non ST-segment elevation acute coronary syndrome The CURE Trial Investigators. NEJM. 2001;345:494-502

  5. ACE INHIBITOR RECOMMENDATIONS SECONDARY PREVENTION An ACE inhibitor in those following a MI, regardless of EF or in those with CAD* along with hypertension (SBP >120 mmHg), LVSD (EF <0.40), heart failure, DM, or CKD. Optional use of an ACE inhibitor in those with low risk CAD*, well controlled CV risk factors, a normal EF, and successful revascularization. ACE=Angiotensin converting enzyme, CAD=Coronary artery disease, CKD=Chronic kidney disease, CV=Cardiovascular, DM=Diabetes mellitus, EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, SBP=Systolic blood pressure *Defined by previous MI or angiographically significant CAD.

  6. ACE INHIBITOR EVIDENCE: SECONDARY PREVENTION HEART OUTCOMES PREVENTION AND EVALUATION (HOPE) STUDY 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 CV DEATH, MI, OR STROKE (%) 0.10 0.05 22% RRR, P<0.001 0.00 0 500 1000 1500 DAYS OF FOLLOW-UP ACE-I reduce CV events in high-risk individuals 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

  7. 0.4 ACE-I 0.35 Placebo 0.3 0.25 0.2 0.15 0.05 0 4 0 1 2 3 ACE INHIBITOR EVIDENCE: SECONDARY PREVENTION SAVE AIRE TRACE RadionuclideEF £ 40% EchocardiogramEF £ 35% Clinical and/or radiographic signs of HF PROBABILITY OF EVENT 0.1 OR: 0.74 (0.66–0.83) YEARS ACE-I provide substantial benefit in post-MI LVSD 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

  8. 256 256 128 128 64 64 32 32 16 16 8 8 4 4 2 2 1 1 0 0 120 140 160 180 70 80 90 100 110 BLOOD PRESSURE: LOWER IS BETTER Ischemic Heart Disease Mortality Age at Risk (Y) Age at Risk (Y) 80-89 80-89 70-79 70-79 60-69 60-69 50-59 50-59 40-49 40-49 Ischemic Heart Disease Mortality Ischemic Heart Disease Mortality Usual Systolic BP (mm Hg) Usual Diastolic BP (mm Hg) BP=Blood pressure Prospective Studies Collaboration. Lancet. 2002;360:1903-1913

  9. BLOOD PRESSURE RECOMMENDATIONS SECONDARY PREVENTION Initiation or maintenance of lifestyle modification in those with a BP >120/80 mmHg. Use of an ACE inhibitor and/or b-blocker in those with a BP >140/90 mmHg*. Other drugs (i.e., thiazide diuretics) should be added in order to achieve the desired BP. ACE=Angiotensin converting enzyme, BP=Blood pressure, CKD=Chronic kidney disease, DM=Diabetes mellitus *A BP >130/80 mmHg should be used for individuals with CKD or DM

  10. BLOOD PRESSURE EVIDENCE: SECONDARY PREVENTION COMPARISON OF AMLODIPINE VS ENALAPRIL TO LIMIT OCCURRENCES OF THROMBOSIS (CAMELOT) TRIAL 1,991 patients with CAD and a DBP <100 mmHg randomized to amloidipine (10 mg), enalapril (20 mg), or placebo for 2 years 130/78 0.25 Placebo Follow-up BP (mmHg) 124/77 Enalapril 0.20 125/77 Amlodipine 0.15 CV event rate* 0.10 0.05 0 0 6 12 18 24 Months A BP <130/80 mmHg is associated with fewer CV events BP=Blood pressure, CAD=Coronary artery disease, CV=Cardiovascular, DBP=Diastolic blood pressure, HF=Heart failure, MI=Myocardial infarction, PAD=Peripheral arterial disease, TIA=Transient ischemic attack *Includes CV death, MI, cardiac arrest, coronary revascularization, hospitalization for HF or angina pectoris, stroke, TIA, development of PAD Nissen S et al. JAMA 2004;292:2217-26.

  11. b-BLOCKER RECOMMENDATIONS* SECONDARY PREVENTION A b-blocker in all patients following a MI. A beta-blocker in all patients with LVSD. A b-blocker in those with other forms of CV disease or DM, unless contraindicated. CV=Cardiovascular, DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction *Relative contraindications include asthma, chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds.

  12. CHOLESTEROL MANAGEMENT GUIDELINES SECONDARY PREVENTION Restriction of saturated fat (<7% of total calories) and cholesterol (<200 mg/day) in all patients. Promotion of daily physical activity and weight management in all patients. Increase in w-3 fatty acid consumption in all patients. LDL-C=Low density lipoprotein cholesterol

  13. CHOLESTEROL MANAGEMENT GUIDELINES (CONTINUED) SECONDARY PREVENTION Initiation or intensification of LDL-C lowering drug therapy in those with a baseline or on-treatment LDL-C level >100 mg/dl. Initiation of LDL-C lowering drug therapy in those with a baseline LDL-C level <100 mg/dl based on clinical judgment. LDL-C=Low density lipoprotein cholesterol

  14. CHOLESTEROL MANAGEMENT GUIDELINES (CONTINUED) GOALS RECOMMENDATIONS As set forth by the Adult Treatment Panel III (ATP III) National Cholesterol Education Program (NCEP) • Obtain a fasting lipid profile in all patients. For those with a myocardial infarction, a fasting lipid profile should be obtained within 24 hrs of admission. • Start therapeutic lifestyle changes in all patients, including: • Reduced intakes of saturated fats (<7% of total calories) and cholesterol (<200 mg/day) • Addition of plant stanols/sterols (2 g/day) and viscous fiber (10-25 g/day) to enhance LDL-C lowering • Weight reduction • Increased physical activity Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486.

  15. ATP III LDL-C GOALS AND CUT-POINTS FOR DRUG THERAPY *Risk factors for cardiovascular disease include: cigarettes smoking, hypertension (blood pressure >140/90 mmHg or on antihypertensive medication, HDL-C <40 mg/dl (>60 mg/dl is a negative risk factor), family history of premature CHD, age >45 years in men or >55 years in women. 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.

  16. PRIMARY THERAPIES TO LOWER LDL-C

  17. 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 30 Atorvastatin Pravastatin 16% RRR 25 20 Recurrent MI or Cardiac Death 15 10 5 P =0.005 0 3 6 9 12 15 18 21 24 27 30 Follow-up (months) Acute intensive therapy significantly reduces the event rate ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction Cannon CP et al. NEJM 2004;350:1495-1504

  18. HMG-COA REDUCTASE INHIBITOR: SECONDARY PREVENTION SCANDINAVIAN SIMVASTATIN SURVIVAL STUDY (4S) 4,444 patients with angina pectoris or previous MI randomized to simvastatin (20-40 mg) or placebo for 5.4 years 30% RRR 11.5 12 8.2 8 Mortality (%) 4 P<0.001 0 Placebo Simvastatin Statins provide significant benefit in those with average LDL-C levels MI=Myocardial infarction, RRR=Relative risk reduction 4S Group. Lancet 1994;344:1383–1389

  19. 0.4 0.6 0.8 1.0 1.2 1.4 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) Statin Better Statin Worse 0.76 (0.72–0.81) P<0.0001 Statins provide significant benefit across a broad range of LDL-C levels CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus, HPS Collaborative Group. Lancet 2002;360:7-22

  20. CIGARETTE SMOKING CESSATION GUIDELINES GOALS RECOMMENDATIONS Complete cessation No environmental tobacco smoke exposure Ask about tobacco use at every visit. In a clear, strong, and personalized manner, advise the patient to stop smoking. Urge avoidance of exposure to secondhand smoke at work and home. Assess the patient’s willingness to quit smoking. Develop a plan for smoking cessation and arrange follow-up. Provide counseling, pharmacologic therapy, and referral to formal smoking cessation programs as indicated.

  21. SMOKING CESSATION PHARMACOTHERAPY* *Pharmacotherapy combined with behavioral support provides the best success rate **Other nicotine replacement therapy options include: nicotine gum, lozenge, inhaler, nasal spray

  22. SMOKING CESSATION PHARMACOTHERAPY: VARENICLINE Two trials compared treatment with varenicline, a nicotine acetylcholine receptor agonist, to treatment with buproprion or placebo. These trials included a total of almost 700 participants. The mean duration of smoking was 25 years. Varenicline yielded higher rates of smoking cessation than buproprion or placebo. Study 1 p<0.001 for V vs B p<0.001 for V vs P Study 2 p<0.001 for V vs B p<0.001 for V vs P JAMA 2006:296:47-55 and JAMA 2006;296:56-63

  23. WEIGHT MANAGEMENT GUIDELINES GOALS RECOMMENDATIONS Calculate BMI* and measure waist circumference as part of evaluation. Monitor response of BMI and waist circumference to therapy. BMI 18.5 to 24.9 kg/m2 Women: <35 inches Men: <40 inches Start weight management and physical activity as appropriate. If BMI and/or waist circumference is above goal, initiate caloric restriction, measures to increase caloric expenditure, and treatment strategies for the metabolic syndrome. 10% weight reduction within the first year of therapy BMI=Body mass index *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.

  24. PREVALENCE OF OBESITY IN U.S. ADULTS 1996 1991 2003 % State Population No Data <10% 10%–14% 15%–19% 20%–24% ≥ 25% Source: CDC Overweight and Obesity

  25. HemorrhagicStroke IschemicStroke Ischemic HeartDisease 4.0 4.0 4.0 2.0 2.0 2.0 Hazard Ratio 1.0 1.0 1.0 0.5 0.5 0.5 16 16 16 20 20 20 24 24 24 28 28 28 32 32 32 36 36 36 Body Mass Index (kg/m2)* CV RISK INCREASES WITH BODY MASS INDEX CV=Cardiovascular 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

  26. DIABETES MELLITUS GUIDELINES GOALS RECOMMENDATIONS Goal HbA1C <7% • Intensive lifestyle modification to prevent the development of DM (especially in those with the metabolic syndrome) • Aggressive management of CV risk factors (i.e., tobacco use, hypertension, dyslipidemia, physical inactivity, and overweight and obese states) • Hypoglycemic therapy to achieve normal to near normal fasting plasma glucose as defined by the HbA1C (<7%) • Weight reduction and exercise • Oral hypoglycemic agents • Insulin therapy • Coordination of diabetic care with the patient’s primary physician and/or endocrinologist. CV=Cardiovascular, DM=Diabetes mellitus, HbA1C=Glycosylated hemoglobin

  27. EXERCISE GUIDELINES GOALS RECOMMENDATIONS • Assess risk, preferably with exercise test, to guide prescription. • Encourage aerobic activity (e.g., walking, jogging, cycling) supplemented by an increase in daily activities (e.g., walking breaks at work, gardening, household work). • Encourage resistance training (e.g., weight machines, free weights) 2 days a week (Class IIb, Level C) • Encourage cardiac rehabilitation for patients with chronic stable angina, recent myocardial infarction, left ventricular systolic dysfunction, or recent coronary artery bypass graft surgery. Minimum: 30 minutes, 5 days per week Optimal: 30 minutes daily

  28. EJECTION FRACTION GUIDELINES SECONDARY PREVENTION Echocardiography in those following a STEMI to re-evaluate ventricular function when results are used to guide therapy*. Echocardiography or radionuclide angiography in those following a NSTE-ACS when results are used to guide therapy*. NSTE-ACS=Non-ST-segment elevation acute coronary syndrome, STEMI=ST-segment elevation myocardial infarction *Includes use of an aldosterone antagonist, digitalis, and/or an implantable cardioverter defibrillator

  29. 20 30 40 50 60 70 80 RELATIONSHIP BETWEEN EF* AND MORTALITY 50 <30 40 30 Cardiac Mortality % 31-35 20 36-45 10 46-53 54-60 >60 0 Ejection Fraction (%) EF=Ejection fraction *Post myocardial infarction Brodie B et al. Am J Cardiol 1992;69:1113

  30. 25 20 15 10 5 0 0 6 12 18 24 30 36 ALDOSTERONE ANTAGONIST: SECONDARY PREVENTION EPLERENONE POCT-ACUTE MYOCARDIAL INFARCTION HEART FAILURE EFFICACY AND SURVIVAL STUDY (EPHESUS) 3,313 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 All Cause Mortality (%) RR = 0.85, P=0.008 Month Aldosterone inhibition provides significant benefit in patients with post-MI heart failure and LVSD EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction Pitt B et al. NEJM 2003;348:1309-21

  31. Additional Marker of Electrical Instability? ICD ALGORITHM AT LEAST ONE MONTH FOLLOWING A MYOCARDIAL INFARCTION EF < 30% EF 31-40% EF > 40% No Yes No ICD. Medical Rx EPS + – EF=Ejection fraction, EPS=Electrophysiology study, ICD=Implantable cardioverter defibrillator, Rx=Treatment, SCD=Sudden cardiac death, NEJM 349:1836,2003

  32. ICD: SECONDARY PREVENTION* Overall death 75% 73% Arrhythmic death 61% 55% 54% % Mortality Reduction w/ ICD Rx 31% 1 2 3 27 Months 39 Months 20 Months EF <35% EF <40% EF <30% *Primary prevention of sudden cardiac death 1 Moss AJ. N Engl J Med. 1996;335:1933-1940 2 Buxton AE. N Engl J Med. 1999;341:1882-1890 3 Moss AF. N Engl J Med. 2002;346:877-883

  33. PREVENTION PYRAMID ASA ACE-I Rehab β-blockers +Primary Secondary Lipids Hypertension Smoking cessation Diabetes +Primordial Primary Physical activity Healthy eating Ideal weight Psychosocial factors Familial predisposition Primordial ACE-1 = angiotensin converting enzyme inhibitor; ASA = aspirin

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