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Management-of-CAD.ppt
- 1. Management of Coronary Artery Disease: Saravanan Kuppuswamy MD Division of Cardiology Department of Internal Medicine University of Missouri Hospital
- 8. Temporal Trends in CAD • CHD is the leading cause of death in adults in US (1/3 of all deaths in subjects over age 35) • Mortality rates for cardiovascular death has fallen in most developed countries 24-28% since 1975 • Estimated that 45 percent of mortality reduction in CHD is due to improvement of medical therapy and 55% is due to risk factor modification
- 9. Etiology • Congenital • Acquired – Infection – Inflammation – Neoplastic
- 10. Management of CAD • Acute • Chronic
- 11. ACS=acute coronary syndrome. UA=unstable angina. Bhatt DL. J Invasive Cardiol. 2003;15:3B-9B. Acute Plaque Rupture (UA/NSTEMI/STEMI) Presence of Multiple Coronary Plaques Persistent Hyperreactive Platelets Vascular Inflammation Clinical Subclinical ACS: The Tip of the Atherothrombotic “Iceberg” NSTEMI=non-ST-segment elevation myocardial infarction. STEMI=ST-segment elevation myocardial infarction.
- 12. Chronic stable angina • Levine’s sign • Exercise capacity may vary • Relieved by nitrates
- 15. Class I Benefit >>> Risk Procedure or treatment SHOULD be performed or administered Class IIa Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure or administer treatment Class IIb Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Procedure or treatment MAY BE CONSIDERED Class III Risk ≥ Benefit No additional studies needed Procedure or treatment should NOT be performed or administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Applying Classification of Recommendations and Level of Evidence
- 16. 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
- 18. A
- 19. Antiplatelet Agents / Anticoagulation Recommendations
- 20. Aspirin Recommendations 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 I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
- 21. Aspirin Evidence: Secondary Prevention Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86. 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 1.0 0.5 0.0 1.5 2.0 Control better Antiplatelet better Effect of antiplatelet therapy* on vascular events** *Aspirin was the predominant antiplatelet agent studied **Vascular events include MI, stroke, or death
- 22. Aspirin Evidence: Dose and Efficacy 0.5 1.0 1.5 2.0 500-1500 mg 34 19 160-325 mg 19 26 75-150 mg 12 32 <75 mg 3 13 Any aspirin 65 23 Antiplatelet Better Antiplatelet Worse Aspirin Dose No. of Trials (%) Odds Ratio for Vascular Events 0 P<.0001 Indirect Comparisons of Aspirin Doses on Vascular Events in High-Risk Patients Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86
- 23. Mechanism of action of nitrates
- 24. B
- 28. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III Start and continue indefinitely in all post MI, ACS, LV dysfunction with or without HF symptoms, unless contraindicated. 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 Recommendations I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
- 29. Phase of Treatment Acute treatment Secondary prevention Overall Total # Patients 28,970 24,298 53,268 0.5 1.0 2.0 RR of death b-blocker better RR (95% CI) Placebo better 0.87 (0.77-0.98) 0.77 (0.70-0.84) 0.81 (0.75-0.87) b-blocker Evidence 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. Summary of Secondary Prevention Trials of b-blocker Therapy CI=Confidence interval, RR=Relative risk
- 30. 6,644 patients with LVEF <0.40 after a MI with or without HF randomized to carvedilol or placebo for 24 months The CAPRICORN Investigators. Lancet. 2001;357:1385–1390. RR 0.77 P=.03 0.7 0.75 0.8 0.85 0.9 0.95 1 0 0.5 1 1.5 2 2.5 Carvedilol Placebo Years Proportion Event-free n=975 n=984 b-blocker Evidence: Post MI with Left Ventricular Dysfunction Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN)
- 31. Study Drug HF Severity Patients (n) Follow-up (years) Mean Dosage Effects on Outcomes CIBIS Bisoprolol* Moderate- Severe 641 1.9 3.8 mg/day All cause mortality 22% (p=NS) CIBIS-II Bisoprolol* Moderate- Severe 2,647 1.3 7.5 mg/day All cause mortality 34% (P<0.0001) BEST Bucindolol* Moderate- Severe 2,708 2.0 152 mg/day All cause mortality 10% (p=NS) MERIT-HF Metoprolol succinate# Mild- Moderate 3,991 1.0 159 mg/day All cause mortality 34% (P=0.0062) MDC Metprolol tartrate* Mild- Moderate 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 Mild- Moderate 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) b-blocker Evidence: Benefit in HF and LVSD *Not an approved indication †Not a planned end point. #Not approved for severe HF or mortality reduction alone
- 32. Goal: <140/90 mm Hg or <130/80 if diabetes or chronic kidney disease I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III Blood Pressure Control Recommendations 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 I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
- 33. Prospective Studies Collaboration. Lancet. 2002;360:1903-1913 Usual Diastolic BP (mm Hg) Usual Systolic BP (mm Hg) Ischemic Heart Disease Mortality 50-59 60-69 70-79 80-89 Age at Risk (Y) 40-49 256 128 64 32 16 8 4 2 1 0 120 140 160 180 50-59 60-69 70-79 80-89 Age at Risk (Y) 40-49 256 128 64 32 16 8 4 2 1 0 80 90 100 110 70 Blood Pressure: Lower is Better Ischemic Heart Disease Mortality Ischemic Heart Disease Mortality BP=Blood pressure
- 34. Veterans Administration, 1967 Veterans Administration, 1970 Hypertension Stroke Study, 1974 USPHS Study, 1977 EWPHE Study, 1985 Coope and Warrender, 1986 SHEP Study, 1991 STOP-Hypertension Study, 1991 MRC Study, 1992 Syst-Eur Study, 1997 Total 0 0.5 1.0 1.5 2.0 0.79 (0.69 to 0.90) He J et al. Am Heart J 1999; 138:211-219 Better than placebo Worse than placebo Blood Pressure: Risk of CHD with Active Treatment CHD=Coronary heart disease
- 35. Yes >100 >160 Stage 2 Hypertension Yes 90–99 140–159 Stage 1 Hypertension Yes 80–89 120–139 Pre- hypertension Encourage <80 <120 Normal With compelling indications Initial drug therapy Lifestyle modification DBP* mmHg SBP* mmHg BP classification JNC VII Guidelines for Management and Treatment ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=b-blocker, BP=Blood pressure, CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure Chobanian AV et al. JAMA. 2003;289:2560-2572 *Treatment determined by highest blood pressure category. †Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. ‡Treat patients with chronic kidney disease or diabetes mellitus to blood pressure goal of <130/80 mmHg. Drug(s) for the compelling indications.‡ Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Drug(s) for compelling indications. ‡
- 36. Modification Recommendation Approximate SBP Reduction Range Weight reduction Maintain normal body weight (BMI=18.5- 24.9) 5-20 mmHg/10 kg weight lost Adopt DASH eating plan 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 JNC VII Lifestyle Modifications for BP Control Chobanian AV et al. JAMA. 2003;289:2560-2572 BMI=Body mass index, SBP=Systolic blood pressure
- 37. Clinical-Trial Basis Compelling Indication ALLHAT, HOPE, ANBP2, LIFE, CONVINCE High CAD Risk ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn, EPHESUS Post-MI MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT, RALES Initial Therapy Options Diuretic, BB, ACEI, CCB BB, ACEI, Aldo Ant Diuretic, BB, ACEI, ARB, Aldo Ant Heart Failure JNC VII Compelling Indications for Drug Classes ACEI=Angiotensin converting enzyme inhibitor, Aldo Ant=Aldosterone antagonist, ARB=Angiotensin receptor blocker, BB=b-blocker, CAD=Coronary artery disease, CCB=Calcium channel blocker, MI=Myocardial Infarction Chobanian AV et al. JAMA. 2003;289:2560-2572 Recurrent Stroke Prevention PROGRESS Diuretic, ACEI NKF-ADA Guideline, UKPDS, ALLHAT NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK Diuretic, BB, ACEI, ARB, CCB ACEI, ARB Diabetes Mellitus Chronic Kidney Disease
- 38. C
- 39. Goal: Complete Cessation and No Exposure to Environmental Tobacco Smoke I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III Cigarette Smoking Recommendations •Ask about tobacco use status at every visit. •Advise every tobacco user to quit. •Assess the tobacco user’s willingness to quit. •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.
- 40. 0.1 1.0 10 Ceased smoking Continued smoking RR (95% Cl) Study Aberg, et al. 1983 0.67 (0.53-0.84) Herlitz, et al. 1995 0.99 (0.42-2.33) Johansson, et al. 1985 0.79 (0.46-1.37) Perkins, et al. 1985 3.87 (0.81-18.37) Sato, et al. 1992 0.10 (0.00-1.95) Sparrow, et al. 1978 0.76 (0.37-1.58) Vlietstra, et al. 1986 0.63 (0.51-0.78) Voors, et al. 1996 0.54 (0.29-1.01) Cigarette Smoking Cessation: Risk of Non-fatal MI* Critchley JA et al. JAMA. 2003;290:86-97. *Includes those with known coronary heart disease CI=Confidence interval, RR=Relative risk
- 41. Risk Category LDL-C and non-HDL- C Goal Initiate TLC Consider Drug Therapy High risk: CHD or CHD risk equivalents (10-year risk >20%) and <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) Very high risk: ACS or established CHD plus: multiple major risk factors (especially diabetes) or severe and poorly controlled risk factors <70 mg/dL, non-HDL-C < 100 mg/dL All patients >100 mg/dL (<100 mg/dL: consider drug options) Grundy, S. et al. Circulation 2004;110:227-39. Lipid Management Goals: NCEP ATP=Adult Treatment Panel, CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol, TLC=Therapeutic lifestyle changes
- 42. Lipid Management Recommendations Start dietary therapy (<7% of total calories as saturated fat and <200 mg/d cholesterol) Adding plant stanol/sterols (2 gm/day) and viscous fiber (>10 mg/day) will further lower LDL Promote daily physical activity and weight management. Encourage increased consumption of omega-3 fatty acids in fish or 1 g/day omega-3 fatty acids in capsule form for risk reduction. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III For all patients
- 43. Lipid Management Recommendations If baseline LDL-C > 100 mg/dL, initiate LDL-lowering drug therapy If on-treatment LDL-C > 100 mg/dL, intensify LDL- lowering 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 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 I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III When LDL lowering medications are used, obtain at least a 30-40% reduction in LDL-C levels. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
- 44. Lipid Management Recommendations If TG are 200-499 mg/dL, non-HDL-C should be < 130 mg/dL Further reduction of non-HDL to < 100 mg/dL is reasonable 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 I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
- 45. 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%) Event Rate Ratio (95% CI) Statin Better Statin Worse 0.4 0.6 0.8 1.0 1.2 1.4 0.76 (0.72–0.81) P<0.0001 Heart Protection Study (HPS) HMG-CoA Reductase Inhibitor: Secondary Prevention 20,536 patients with CAD, other occlusive arterial disease, or DM randomized to simvastatin (40 mg) or placebo for 5.5 years CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus, HPS Collaborative Group. Lancet 2002;360:7-22
- 46. Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)—TIMI 22 Study 3 6 9 12 15 18 21 24 27 30 Follow-up (months) 30 25 20 15 10 5 0 P =0.005 Recurrent MI or Cardiac Death 16% RRR Atorvastatin Pravastatin ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction Cannon CP et al. NEJM 2004;350:1495-1504 HMG-CoA Reductase Inhibitor: Secondary Prevention 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months
- 47. LaRosa JC et al. NEJM. 2005;352:1425-1435 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. 30 25 20 15 10 5 0 0 70 90 110 130 150 170 190 210 LDL-C (mg/dL) TNT (atorvastatin 80 mg/d) TNT (atorvastatin 10 mg/d) HPS CARE LIPID LIPID CARE HPS Event (%) 4S 4S Statin Placebo Relationship between LDL Levels and Event Rates in Secondary Prevention Trials of Patients with Stable CHD HMG-CoA Reductase Inhibitor: Secondary Prevention
- 48. HDL-C=High-density lipoprotein cholesterol, LDL-C=Low-density lipoprotein cholesterol, TC=Total cholesterol, TG=Triglycerides *Daily dose of 40mg of each drug, excluding rosuvastatin. Therapy TC LDL HDL TG Patient tolerability Statins* 19-37% 25-50% 4-12% 14-29% Good Ezetimibe 13% 18% 1% 9% Good Bile acid sequestrants 7-10% 10-18% 3% Neutral or Poor Nicotinic acid 10-20% 10-20% 14-35% 30-70% Reasonable to Poor Fibrates 19% 4-21% 11-13% 30% Good Lipid Management Pharmacotherapy
- 49. Lipid Management Goal LDL-C should be less than 100 mg/dL Further reduction to LDL-C to < 70 mg/dL is reasonable I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III *Non-HDL-C = total cholesterol minus HDL-C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III If TG >200 mg/dL, non-HDL-C should be < 130 mg/dL*
- 50. D
- 51. *Trans fatty acids also raise LDL-C and should be kept at a low intake. Note: Regarding total calories, balance energy intake and expenditure to maintain desirable body weight. <200 mg/d Cholesterol ~15% of total calories Protein 20–30 g/d Fiber 50%–60% of total calories Carbohydrate (esp. complex carbs) 25%–35% of total calories Total fat Up to 20% of total calories Monounsaturated fat Up to 10% of total calories Polyunsaturated fat <7% of total calories Saturated fat* Recommended Intake Nutrient Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497. ATP III Dietary Recommendations ATP=Adult Treatment Panel
- 52. Weight Management Recommendations I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III Goal: BMI 18.5 to 24.9 kg/m2 Waist Circumference: Men: < 40 inches Women: < 35 inches I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III 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. 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. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
- 53. Mhurchu N et al. Int J Epidemiol 2004;33:751-758 0.5 1.0 2.0 4.0 16 20 24 28 32 36 Body Mass Index (kg/m2)* Hazard Ratio 0.5 1.0 2.0 4.0 16 20 24 28 32 36 0.5 1.0 2.0 4.0 16 20 24 28 32 36 Hemorrhagic Stroke Ischemic Stroke Ischemic Heart Disease 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.
- 54. Grundy, et al. Diagnosis and management of the metabolic syndrome: an AHA/NHLBI Scientific Statement. Circulation 2005;112:2735-2752. Risk Factor Defining Level Waist circumference (abdominal obesity) >40 in (>102 cm) in men >35 in (>88 cm) in women Triglyceride level >150 mg/dl HDL-C level <40 mg/dl in men <50 mg/dl in women Blood pressure >130/>85 mmHg Fasting glucose >100 mg/dl Definition of the Metabolic Syndrome Defined by presence of >3 risk factors HDL-C=High-density lipoprotein cholesterol
- 55. 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 Lifestyle modification reduces the risk of developing DM Metabolic Syndrome: Risk of Developing DM Diabetes Prevention Program (DPP) Knowler WC et al. NEJM 2002;346:393-403 *Includes 7% weight loss and at least 150 minutes of physical activity per week Placebo Metformin Lifestyle modification Incidence of DM (%) 20 40 0 1 4 2 3
- 56. Diabetes Mellitus Recommendations I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III Goal: Hb A1c < 7% I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III Lifestyle and pharmacotherapy to achieve near normal HbA1C (<7%). Vigorous modification of other risk factors (e.g., physical activity, weight management, blood pressure control, and cholesterol management as recommended). Coordinate diabetic care with patient’s primary care physician or endocrinologist. ) HbA1c = Glycosylated hemoglobin I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
- 57. E
- 58. Physical Activity Recommendations Assess risk with a physical activity history and/or an exercise test, to guide prescription 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 Advise medically supervised programs for high-risk patients (e.g. recent acute coronary syndrome or revascularization, I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III Goal: 30 minutes 7 days/week, minimum 5 days/week I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
- 59. 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 Exercise Evidence: Mortality Risk
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- 62. ACE Inhibitor Recommendations Use in all patients with LVEF < 40%, and those with diabetes or chronic kidney disease indefinitely, unless contraindicated Consider for all other patients Among lower risk patients with normal LVEF where cardiovascular risk factors are well controlled and where revascularization has been performed, their use may be considered optional I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III ACE=Angiotensin converting enzyme, LVEF= left ventricular ejection fraction I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
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- 66. STRIVETM
- 67. STEMI Clinical finding EKG Serum markers Risk assessment Non-cardiac chest pain Stable angina UA NSTEMI Negative Positive ST-T wave changes ST elevation Low probability Medium-high risk Thrombolysis Primary PCI Aspirin + GP IIb/IIIa inhibitor clopidogrel + heparin/ LMWH + anti-ischemic Rx Early invasive Rx Discharge Negative Diagnostic rule out MI/ACS pathway STEMI Negative Atypical pain Low risk Aspirin, heparin/low-molecular- weight heparin (LMWH) + clopidogrel Anti-ischemic Rx Early conservative therapy Ongoing pain DM=diabetes mellitus. Cannon, Braunwald. Heart Disease. 2001. Rest pain, Post-MI, DM, Prior Aspirin Exertional pain The Spectrum of ACS
- 68. Acute Coronary Syndromes: Management of STEMI
- 73. Stents
- 74. Acute Coronary Syndromes: Management of UA/NSTEMI
- 75. Acute Management of UA/NSTEMI Anti-Ischemic Therapy • Oxygen, bed rest, ECG monitoring • Nitroglycerin • b-Blockers • ACE inhibitors UA, unstable angina; NSTEMI, non-ST-segment elevation myocardial infarction; ECG, electrocardiogram; ACE, angiotensin-converting enzyme. Braunwald E, et al. J Am Coll Cardiol. 2000;36:970-1062. Antithrombotic Therapy • Antiplatelet therapy • Anticoagulant therapy
- 76. Rationale for Use: Pharmacologic Intervention in Thrombosis UFH=unfractionated heparin. LMWH=low-molecular-weight heparin ADP=adenosine diphosphate. TFPI=tissue factor pathway inhibitor Selwyn A. Am J Cardiol. 2003;91:3H-11H. Coagulation cascade Platelets LMWH Thienopyridines GP IIb/IIIa inhibitors Thrombolytics LMWH UFH LMWH UFH Direct thrombin inhibitors Tissue factor Factor Xa Prothrombin Thrombin Platelets A2 vWF ADP Activated platelets Fibrinogen cross-linking Platelet aggregation Aspirin Fibrinogen Fibrin Fibrin degradation Collagen Leukocytes TFPI Thromboxane Plasmin Thrombus
- 78. Efficacy of Aspirin Doses on Vascular Events in High Risk Patients Adapted with permission from the BMJ Publishing Group. Anti-thrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86. 0 0.5 1.0 1.5 2.0 500–1500 mg 34 19 160–325 mg 19 26 75–150 mg 12 32 <75 mg 3 13 Any aspirin 65 23 Anti - platelet Better Anti - platelet Worse Aspirin Dose # Trials OR* (%) *Odds reduction. Treatment effect P < 0.0001. Odds Ratio
- 79. RR: Death/MI ASA Alone 68/655=10.4% Heparin + ASA 55/698=7.9% B B B B B B B 0.1 1 10 Summary Relative Risk 0.67 (0.44-0.1.02) Theroux RISC Cohen 1990 ATACS Holdright Gurfinkel Comparison of Heparin + ASA vs ASA Alone ASA, acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease; ATACS, Antithrombotic Therapy in Acute Company Syndromes; RR, relative risk; MI, myocardial infarction. Oler A, et al. JAMA. 1996;276:811-815. (with permission)
- 81. TIMI, Thrombosis in Myocardial Infarction; ESSENCE, Efficacy and Safety of Subcutaneous Enozapam in Non–Q-Wave Coronary Events; UHF, unfractionated heparin; ENOX, enoxaparin; MI, myocardial infarction; OR, odds ratio. Antman EM, et al. Circulation. 1999;100:1602-1608. (with permission) TIMI IIB/ESSENCE Metanalysis: Enoxaparin vs Unfractionated Heparin 8.6 7.1 0.82 (0.69-0.97) 18 .02 6.5 5.2 0.79 (0.65-0.96) 21 .02 5.3 4.1 0.77(0.62-0.95) 23 .02 1.8 1.4 0.80 (0.55-1.16) 20 .24 0.5 1 2 Day 2 8 14 43 UFH (%) ENOX (%) OR (95 CI) Favors ENOX Favors UFH P OR Death or MI %
- 82. LMWH Limitations • Indirect inhibition: dependent on antithrombin • Inability to inhibit clot-bound thrombin • Catheterization lab: slower onset, longer half- life, and with enoxaparin, no standard test to measure levels/effect • CABG: concerns regarding the long half-life • Monitoring for Factor Xa: possible, but what is the therapeutic target, increased time, expense? • Not all LMWHs are the same CABG=coronary artery bypass graft.
- 83. 0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 Cumulative Hazard Rate Clopidogrel + Aspirin* 3 6 9 Placebo + Aspirin* Months of Follow-Up P<0.001 N=12,562 0 12 *Other standard therapies were used as appropriate. CV=cardiovascular. CURE Trial Investigators. N Engl J Med. 2001;345:494-502. 20% Relative-risk Reduction CURE: Primary Endpoint: MI/Stroke/CV Death
- 84. Before PCI Post-PCI Placebo GP IIb/IIIa Inhibitor PCI n=2754 p=0.001 +24 h +48 h 8.0% 4.9% 0% 2% 4% 6% 8% 10% Death/MI 0 2.9% 0% 2% 4% 6% 8% 10% n=12,296 p=0.001 +24 h +48 h +72 h 4.3% Death/MI Boersma E, et al. Circulation. 1999;100:2045-2048. Early Use of GP IIb/IIIa Inhibition Improves PCI: CAPTURE, PURSUIT, PRISM-PLUS
- 85. 4.59% 2.59% 0% 2% 4% 6% 8% In-hospital mortality (%) No early GP IIb/IIIa inhibitor (n=26,596) Early GP IIb/IIIa inhibitor (n=14,296) In-hospital Mortality is Lower With Early GP IIb/IIIa Inhibitor Use (within 24 hrs) † ∆ 42% p<0.0001 Includes patients who received late GP IIb/IIIa inhibitor (> 24 hrs) therapy. † Unadjusted for risk.
- 86. TIMI, thrombosis in myocardial infarction; UA, unstable angina; NSTEMI, non–ST-segment elevation myocardial infarction; CAD, coronary artery disease. Antman EM, et al. JAMA. 2000;284:835-842. TIMI Risk Score for UA/NSTEMI: 7 Independent Predictors – Aged ≥65 years – ≥3 CAD risk factors – Prior CAD (stenosis >50%) – Aspirin in last 7 days – >2 anginal events in ≤24 hours – ST deviation – Elevated cardiac markers (CK-MB or troponin)
- 87. TIMI risk score predicts 30 day mortality after a myocardial infarction The TIMI risk score has a continuous association with 30-day mortality in patients with an ST elevation (STE) myocardial infarction who are eligible for fibrinolytic therapy. Morrow, DA, Antman, EM, Charlesworth, A, et al Circulation 2000; 102:2031.
- 88. TIMI risk score predicts 14 day outcome for NSTEMI and UA The TIMI risk score has a continuous association with 14-day mortality, recurrent MI and target vessel revascularization in patients with an NSTEMI and unstable angina (UA) Antman, EM, Cohen, et al, JAMA 2000; 284:835.
- 89. STRIVETM
- 90. STRIVETM
- 91. STRIVETM
- 92. Chest Pain Classification/Triage Class I Class II Class III Class IV Class V Class “x”
- 93. Class I • STEMI Chest pain with STE or new LBBB • Acute revascularization followed by CICU admission
- 94. Class II • Unstable Angina/NSTEMI (high risk) – Positive initial cardiac markers – ST depression > 1mm in two contiguous leads – TIMI risk score > 5 – Continued angina requiring IV NTG drip – CHF – SBP < 90mmHg or > 180mmHg – New mitral regurgitaiton – Recent ACS (< 30 days) • Admit to CICU by cardiology
- 95. Class III • Unstable Angina – No initial increase in cardiac markers – Normal ECG or ST depression < 1mm – No CHF – No recent ACS – TIMI risk score 3-4 • Admit to telemetry by cardiology
- 96. Class IV • Unstable Angina with normal ECG – No initial increase in cardiac markers – No history of CAD – TIMI risk score < 3 – No ongoing or recurring pain • Admit to Chest Pain Service or Chest Pain Center in ER
- 97. Class V • Non-cardiac Chest Pain • Workup in ER with appropriate referral
- 98. Class “x” • Critical causes of acute chest pain other than ACS or ACS combined with other acute critical/life-threatening illnesses • Admit to intensive care (MICU, SICU or CICU) as appropriate