American Osteopathic College of Occupational and Preventive Medicine 2012 Mid-Year Educational Conference St. Petersburg, Florida

Transcription

1 The 21 st Century Paradigm Shift: Prevention Rather Than Intervention for the Treatment of Stable CHD The Economic Burden of Cardiovascular Diseases Basil Margolis MD, FACC, FRCP Director, Preventive Cardiology Program The Heart and Vascular Institute Saint Joseph s Hospital, Atlanta Estimated direct and indirect costs of major cardiovascular diseases and stroke United States Source: NHLBI. Obesity in Children & Adolescents is Increasing at an Alarming Rate Percent of Population Obesity is defined as a BMI of 30.0 or greater. (NHANES: ) U.S. Adult Obesity Rates 2010 Adapted from E-1

2 Earlier Intervention in the Management of Hypercholesterolemia We are initiating treatment of elevated cholesterol (and other risk factors) too late in life Starting treatment at age 30 years instead of age 60 years might very well prevent not just 30% of cardiac events, as in the 5 year statin trials, but perhaps as many as 60% Steinberg D. J Am Coll Cardiol 2010;56: Atherosclerosis Timeline The most common side effect of intensive statin therapy is that of longevity Case History 30 yr old man referred for risk evaluation TC 240 mg/dl HDL 45 mg/dl SBP 135 mm Hg Cigarette smoker Negative family history No other risk factors Case History cont 10 year Framingham Risk Score of 6% ATP III guidelines advise drug treatment of hypercholesterolemia in this man would be inappropriate Moving the clock forward 30 years with all the numbers remaining the same except patient is now 60 years old 10 year Framingham risk is now 20% and drug Rx is now recommended E-2

3 Case History Cont. Rethinking Initiation of Preventive Criteria in ATP IV In the intervening 30 years the extent of his coronary atherosclerosis has relentlessly progressed We have lost 30 years during which it might have been possible to slow the progression of atherosclerosis and possibly even prevent a cardiac event Calculating risk based on the 10 year probability of a cardiac event is misguided as this is very heavily weighted by age ATP IV will most likely recommend calculating the FRS over a 30 year period rather than the current 10 year period Forrester JS. J Am Coll Cardiol 2010;56: Framingham 10 year versus 30 year Risk Intensive LDL Lowering Reduces CHD Events in Primary Prevention Rethinking the LDL-C Target Cost Effectiveness of Statin Therapy for Primary Prevention ATP-III treatment goals for LDL-C are far too high given current data: ATP-IV Low Risk LDL < 160 mg/dl 130 Inter Risk LDL < 130 mg/dl 100 High Risk LDL < 100 mg/dl 70 Using these probable ATP IV treatment levels for LDL-C We could avert a further 14,000 CHD deaths/year Save over $1.4 billion/year compared with current levels of treatment Be highly cost effective assuming a generic statin cost of $4 per month Lazar LD et al. Circulation 2011;124: E-3

4 Most People who Develop CHD Have Normal LDL-C Values Heart attack with normal LDL Of 136,905 patients hospitalized with MI, more than 75% had LDL levels below 130 mg/dl Sachdeva et al. AHJ, Vol 157, Jan 2009 Patient History 58 year old man, overweight with high cholesterol and HTN, well controlled on a statin drug and blood pressure medication Works out everyday on an exercise bike Asymptomatic cardiac status Positive CAC scan Normal exercise stress test April 2008 Died of a heart attack June 2008 NCEP Adult Treatment III Guidelines Tim Russert Total cholesterol 160 mg/dl LDL 67 mg/dl HDL 32 mg/dl Triglycerides 300 mg/dl Waist Circumference >40 inches Once target LDL-C goals have been achieved with statins, consideration should be given to fibrate or niacin therapy to optimize triglyceride and HDL-C levels. E-4

5 Questions Regarding AIM-HIGH Study Design AIM HIGH Study Relatively small number of patients makes study underpowered LDL already reduced to <70 mg/dl with simvastatin possibly minimized the added benefit of niacin The placebo arm actually contained low dose niacin to simulate flushing! Study too short to see any clinical benefit. Coronary Drug Project only showed niacin benefits after 10 to 15 years 3,414 patients with known CHD on statin therapy but with residual risk of high TG and low HDL Randomized to simvastatin plus high dose niacin or placebo Despite significant increase in HDL-C and lowering of TG in niacin arm, no overall effect on rate of cardiovascular events was observed Study terminated early after just 32 months HPS2-THRIVE Study HPS2-THRIVE Study 25,000 patients enrolled with pre-existing CVD All receiving simvastatin 40 mg plus ezetimibe 10 mg, if necessary, to achieve LDL-C of <70 mg/dl Randomized to ER Niacin / laropiprant 2g vs placebo Primary endpoints are MI, coronary death, stroke or coronary revascularization 6 year follow-up terminating in 2013 Does extended release niacin / laropiprant prevent vascular events when added to therapy in high-risk patients who are already receiving intensive LDL-lowering statin treatment? Optimal Medical Therapy COURAGE Trial Pharmacologic Compared optimal medical therapy (OMT) alone versus OMT plus PCI in 2,287 patients with stable CAD Patients were followed for 7 years Anti-platelet: aspirin; clopidogrel in accordance with established practice standards Statin: simvastatin ± ezetimibe or ER niacin ACE Inhibitor or ARB: lisinopril or losartan Beta-blocker: long-acting metoprolol Calcium channel blocker: amlodipine Nitrate: isosorbide 5-mononitrate Boden WE. N Engl J Med 2007;356: E-5

6 Optimal Medical Therapy Lifestyle Smoking cessation Exercise program Nutrition counseling Weight control BARI 2D Trial: Primary Endpoint BARI 2D Study Group p = 0.97 Death (%) Compared intensive medical therapy (IMT) alone versus revascularization plus IMT in patients with type 2 diabetes and stable CHD Both arms had similar rates of cardiac mortality, MI or stroke through 5 years of follow-up n =155 n =161 N Engl J Med 2009;360: Copyleft Clinical Trial Results. You Must Redistribute Slides E-6 BARI 2D Study Group, NEJM 2009

7 Cardiovascular Event (%) BARI 2D Trial: Secondary Endpoints n=138 n=118 Coronary Stenting vs Medical Therapy for Stable CAD: Less is More Meta-analysis of 8 trials comparing stenting versus medical therapy in 7229 patients with stable CAD Mean follow-up 4.3 years No evidence of benefit for stenting versus medical therapy in preventing death, nonfatal MI, unplanned revascularization or angina n=283 n=30 n=33 n=266 Stergiopoulos K, Brown DL. Arch Intern Med 2012 ; 172 : BARI 2D Study Group, NEJM 2009 Most Heart Attacks Arise From Smaller Narrowings Adapted from Falk et al. Circulation. 1995;92: What hath COURAGE Wrought? What Hath COURAGE Wrought? 467,211 patients with stable CAD reviewed from the National Cardiovascular CathPCI Data Registry between 2005 and 2009 Compared the use of OMT versus PCI before and after the publication of the COURAGE trial in 2007 No significant change in physician treatment patterns This study demonstrates an immense gap in quality of care of patients with stable CAD. The underuse of OMT in such a large number of eligible patients is concerning and invokes the need for dedicated quality improvement efforts to optimize the use of appropriate medical therapy. The irrational exuberance for intervention. Borden et al. JAMA 2011;305: Borden et al. JAMA 2011;305:1882=1889. E-7

8 Affects of Vitamin D Deficiency on the Cardiovascular System What about Vitamin D and Omega-3 supplements? Vascular smooth muscle proliferation Inflammation Vascular calcification Thrombosis Activates the renin-angiotensin system Giovannucci E et al. Arch Intern Med 2008;168: Institute of Medicine 2011 Consensus Report on Vitamin D Omega-3 Fish Oils and Heart Disease Anti-arrhythmic In a review of nearly 1000 scientific studies on Vitamin D reduces sudden cardiac death Anti-inflammatory There is clear evidence that Vitamin D has bone benefits, but current research is inconclusive as to whether higher Vitamin D intake can reduce the risk for cancer, heart disease, stroke or other chronic diseases. reduces plaque rupture Anti-thrombotic reduces blood clots Lower triglycerides reduces plaque build up Institute of Medicine 2010 Consensus Report: The National Academies Press Omega-3 Fish Oils and Heart Disease The VITamin D and OmegA-3 TriaL (VITAL) Enrolling 20,000 healthy men and women No prior medical history Will investigate whether taking vitamin D (2000 IU) or omega-3 fatty acids (1 gram) alone or in combination reduces the risk for developing cancer, heart disease or stroke Follow-up 5 years The prevention trials have all been in high risk populations either post MI or with multiple cardiac risk factors The AHA therefore recommends 1000 mg of EPA and DHA per day only for people with established heart disease E-8

9 Deaths from cardiovascular disease United States: Source: NCHS and NHLBI. E-9