Disclosures (with apologies to the Wizard of Oz) A Brain; Heart; and COURAGE

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1 2008 Update: Tools for the Management of Stable Angina Disclosures (with apologies to the Wizard of Oz) A Brain; Heart; and COURAGE Daniel Edmundowicz, MS, MD, FACC Associate Professor Of Medicine Director, Preventive Cardiology Consultant: GNC, Inc.; Merck and Co. Inc. CME and non CME Speaker: ScheringPlough Unshakable conviction that atherosclerosis is a preventable common source epidemic. Late stages of coronary artery disease Frank Netter s Stable Angina Coronary Artery Disease Timeline Arterial Wall: Structure and Function 1

2 Vascular endothelium modification in atherosclerosis Plaque formation: The fatty streak Plaque Rupture 2

3 Different types of vulnerable plaque Different types of vulnerable plaque Naghavi et al. Circ 108 (14): (2003) Naghavi et al. Circ 108 (14): (2003) Plaque characteristics and risk Electron Beam CT Scan of the Heart Naghavi et al. Circ 108 (14): (2003) Predictive Value of Coronary Calcification O R asymptomatic subject Age:53±11 yrs Follow-up: 3.6 years Events: 39 CHD events CAC> Age High Cholesterol 14.3 Hypertension Diabetes CAC>160 CAC score Event rate Risk of All Cause Mortality in Framingham Risk Categories Low Risk n=1,302 Intermediate Risk n=5,876 High Risk n=3,194 CAC score < >1000 Arad et al J Am Coll Cardiol Shaw L, Raggi P et al Radiology

4 CHD is a common source epidemic with a long incubation period. The common source is primarily saturated fatty acids and dietary cholesterol.. Lewis H. Kuller, MD, DrPH Department of Epidemiology, Graduate School of Public Health University of Pittsburgh Current Cardiovascular Risk Reports 2008, 2:9-14 HMG-CoA Reductase Inhibitor: Secondary Prevention Relationship between LDL Levels and Event Rates in Secondary Prevention Trials of Patients with Stable CHD Event (%) LDL-C (mg/dl) 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. Statin Placebo 4S LIPID LIPID CARE CARE HPS HPS TNT (atorvastatin 10 mg/d) TNT (atorvastatin 80 mg/d) S LaRosa JC et al. NEJM. 2005;352: 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 LDL-C and non-hdl- C Goal <100 mg/dl if TG > 200 mg/dl, non-hdl-c should be < 130 mg/dl <70 mg/dl, non-hdl-c < 100 mg/dl Initiate TLC 100 mg/dl All patients Consider Drug Therapy >100 mg/dl (<100 mg/dl: consider drug options) >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:

5 Intention to treat LDL-C levels and CHD risk Intention to treat LDL-C levels and CHD risk by presence of risk factors Am J Cardiol 2006;98: Am J Cardiol 2006;98: Conventional Wisdom: Treatment assumptions in CAD Management Is aggressive medical therapy enough?? Patients with symptomatic CAD and chronic angina who have significant coronary stenoses need revascularization Revascularization is required to improve prognosis. PCI is less invasive than CABG surgery (i.e., is safer) and, therefore, should be selected Do you want that with or without angioplasty? Background More than 1 million PCI procedures are performed in the U.S. annually, the great majority of which are undertaken electively in patients with stable CAD Although successful PCI of flow-limiting stenoses might be expected to reduce the rate of death, MI or hospitalization for ACS, prior studies have shown only that PCI decreases the frequency of angina and improves short-term exercise performance COURAGE Clinical Outcomes Utilizing Revascularization and Aggressive Guideline-Driven Drug Evaluation 5

6 Hypothesis PCI + Optimal Medical Therapy will be Superior to Optimal Medical Therapy Alone Design RRandomization to PCI + Optimal Medical Therapy vs Optimal Medical Therapy alone IIntensive, guideline-driven medical therapy and lifestyle intervention in both groups 2.5 to 7 year (mean 4.6 year) follow-up Inclusion Criteria MMen and Women 11, 2, or 3 vessel disease (> 70% visual stenosis of proximal coronary segment) Anatomy suitable for PCI CCCS Class I-III angina OObjective evidence of ischemia at baseline ACCS/AHA Class I or II indication for PCI Optimal Medical Therapy AAnti-platelet: aspirin; clopidogrel in accordance with established practice standards SStatin: simvastatin ± ezetimibe or ER niacin AACE Inhibitor or ARB: lisinopril or losartan BBeta-blocker: long-acting metoprolol CCalcium channel blocker: amlodipine NNitrate: isosorbide 5-mononitrate Long term improvement in treatment targets Treatment Targets Baseline 60 Months Survival free of death of any cause and myocardial infarction PCI +OMT OMT PCI +OMT OMT Optimal Medical Therapy (OMT) SBP DBP Total Cholesterol mg/dl LDL mg/dl HDL mg/dl TG mg/dl BMI Kg/M² Moderate Activity (5x/week) 131 ± ± ± ± ± ± ± % 130 ± ± ± ± ± ± ± % 124 ± ± ± ± ± ± ± % 122 ± ± ± ± ± ± ± % PCI + OMT Hazard ratio: % CI ( ) P = Years 7 6

7 Survival free of hospitalization for ACS OMT PCI + OMT Hazard ratio: % CI ( ) P = Subgroup analysis Baseline Characteristics Hazard Ratio (95% Cl) PCI Medical Therapy Myocardial Infarction Yes 1.15 ( ) No 0.65 ( ) Extent of CAD Multi-vessel disease 1.10 ( ) Single-vessel disease 1.00 ( ) Diabetes Yes 1.08 ( ) No 0.87 ( ) Angina CCS 0-I 1.27 ( ) CCS II-III 0.71 ( ) Ejection Fraction 50% 1.06 ( ) > 50% 1.06 ( ) Previous CABG No 1.06 ( ) Yes 1.06 ( ) Conclusion AAs an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, MI, or other major cardiovascular events when added to optimal medical therapy AAs expected, PCI resulted in better angina relief during most of the follow-up period, but medical therapy was also remarkably effective, with no between group difference in angina-free status at 5 years "The benefits of angioplasty in STEMI patients have created a belief that because the procedure is identical to that which is undertaken electively in stable patients, the benefit that accrues in the acute patients will likewise accrue in the chronic patients, and that has become the conventional wisdom." Boden,