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Management of Coronary Artery Disease:

Management of Coronary Artery Disease:. Saravanan Kuppuswamy MD Division of Cardiology Department of Internal Medicine University of Missouri Hospital. Coronary blood supply. Micro circulation. Temporal Trends in CAD.

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Management of Coronary Artery Disease:

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  1. Management of Coronary Artery Disease: Saravanan Kuppuswamy MD Division of Cardiology Department of Internal Medicine University of Missouri Hospital

  2. Coronary blood supply

  3. Micro circulation

  4. 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

  5. Etiology • Congenital • Acquired • Infection • Inflammation • Neoplastic

  6. Management of CAD • Acute • Chronic

  7. ACS: The Tip of the Atherothrombotic “Iceberg” Acute Plaque Rupture (UA/NSTEMI/STEMI) Clinical Subclinical Presence of Multiple Coronary Plaques Vascular Inflammation Persistent Hyperreactive Platelets ACS=acute coronary syndrome. UA=unstable angina. Bhatt DL. J Invasive Cardiol. 2003;15:3B-9B. NSTEMI=non-ST-segment elevation myocardial infarction. STEMI=ST-segment elevation myocardial infarction.

  8. Chronic stable angina • Levine’s sign • Exercise capacity may vary • Relieved by nitrates

  9. CCS classification

  10. Applying Classification of Recommendations and Level of Evidence

  11. Components of Secondary Prevention

  12. ABCDE Of Management

  13. A

  14. Antiplatelet Agents / Anticoagulation Recommendations

  15. 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

  16. 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 Antiplatelet better Control better 0.0 0.5 1.0 1.5 2.0 Aspirin Evidence: Secondary Prevention Effect of antiplatelet therapy* on vascular events** *Aspirin was the predominant antiplatelet agent studied **Vascular events include MI, stroke, or death Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86.

  17. Odds Ratio for Vascular Events 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 P<.0001 0 0.5 1.0 1.5 2.0 Antiplatelet Better Antiplatelet Worse Aspirin Evidence: Dose and Efficacy Indirect Comparisons of Aspirin Doses on Vascular Events in High-Risk Patients Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86

  18. Mechanism of action of nitrates

  19. B

  20. b-blocker Recommendations

  21. IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I b-blocker Recommendations 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

  22. b-blocker Evidence Summary of Secondary Prevention Trials of b-blocker Therapy Total # Patients Phase of Treatment RR (95% CI) 28,970 0.87 (0.77-0.98) Acute treatment 24,298 0.77 (0.70-0.84) Secondary prevention 53,268 0.81 (0.75-0.87) Overall 0.5 1.0 2.0 RR of death b-blocker better Placebo better CI=Confidence interval, RR=Relative risk 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.

  23. 1 0.95 n=975 0.9 Carvedilol Proportion Event-free n=984 0.85 0.8 Placebo 0.75 RR 0.77 P=.03 0.7 0 0.5 1 1.5 2 2.5 Years b-blocker Evidence: Post MI with Left Ventricular Dysfunction 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 The CAPRICORN Investigators. Lancet. 2001;357:1385–1390.

  24. 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

  25. Blood Pressure Control Recommendations Goal: <140/90 mm Hg or <130/80 if diabetes or chronic kidney disease 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

  26. 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 Ischemic Heart Disease Mortality Ischemic Heart Disease Mortality 40-49 40-49 Usual Systolic BP (mm Hg) Usual Diastolic BP (mm Hg) BP=Blood pressure Prospective Studies Collaboration. Lancet. 2002;360:1903-1913

  27. Blood Pressure: Risk of CHD with Active Treatment 0.79 (0.69 to 0.90) 0 2.0 0.5 1.5 1.0 CHD=Coronary heart disease Better than placebo Worse than placebo He J et al. Am Heart J 1999; 138:211-219

  28. JNC VII Guidelines for Management and Treatment BP classification SBP* mmHg DBP* mmHg Lifestyle modification Initial drug therapy With compelling indications Normal <120 <80 Encourage Drug(s) for compelling indications. ‡ Pre- hypertension 120–139 80–89 Yes Stage 1 Hypertension 140–159 90–99 Yes Drug(s) for the compelling indications.‡ Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Stage 2 Hypertension >160 >100 Yes 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 *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. Chobanian AV et al. JAMA. 2003;289:2560-2572

  29. JNC VII Lifestyle Modifications for BP Control BMI=Body mass index, SBP=Systolic blood pressure Chobanian AV et al. JAMA. 2003;289:2560-2572

  30. JNC VII Compelling Indications for Drug Classes Compelling Indication Initial Therapy Options Clinical-Trial Basis Heart Failure Diuretic, BB, ACEI,ARB, Aldo Ant MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT, RALES Post-MI BB, ACEI, Aldo Ant ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn, EPHESUS High CAD Risk Diuretic, BB, ACEI, CCB ALLHAT, HOPE, ANBP2,LIFE, CONVINCE Diabetes Mellitus Diuretic, BB, ACEI,ARB, CCB NKF-ADA Guideline,UKPDS, ALLHAT NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK Chronic Kidney Disease ACEI, ARB Recurrent Stroke Prevention Diuretic, ACEI PROGRESS 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

  31. C

  32. 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. • 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.

  33. 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* RR (95% Cl) Study 10 0.1 1.0 Ceased smoking Continued smoking • *Includes those with known coronary heart disease • CI=Confidence interval, RR=Relative risk • Critchley JA et al. JAMA. 2003;290:86-97.

  34. Lipid Management Goals: NCEP 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.

  35. IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I Lipid Management Recommendations For all patients 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.

  36. I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III 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: 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 When LDL lowering medications are used, obtain at least a 30-40% reduction in LDL-C levels.

  37. I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I 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 niacinbefore LDL lowering therapy; and treat LDL-C to goal after TG-lowering therapy. Achieve non-HDL-C < 130 mg/dL, if possible

  38. 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 CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus, HPS Collaborative Group. Lancet 2002;360:7-22

  39. 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) 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 ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction Cannon CP et al. NEJM 2004;350:1495-1504

  40. 30 4S 25 4S 20 LIPID Event (%) 15 LIPID CARE CARE 10 HPS HPS TNT (atorvastatin 10 mg/d) 5 TNT (atorvastatin 80 mg/d) 0 0 70 90 110 130 150 170 190 210 LDL-C (mg/dL) HMG-CoA Reductase Inhibitor: Secondary Prevention Relationship between LDL Levels and Event Rates in Secondary Prevention Trials of Patients with Stable CHD Statin Placebo 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

  41. Lipid Management Pharmacotherapy 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.

  42. I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III I I I IIa IIa IIa IIa IIb IIb IIb IIb III III III III Lipid Management Goal LDL-C should be less than 100 mg/dL 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

  43. D

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