Preventing Cardiovascular Events Primary and Secondary November 8 th 2014 Slides by Dr Dharmesh Patel and Arie Szatkowski Last Minute Presentation by Dr

Preventing Cardiovascular Events Primary and Secondary November 8 th 2014 Slides by Dr Dharmesh Patel and Arie Szatkowski Last Minute Presentation by Dr Arie Szatkowski

NBCs Tim Russert dies at 58 Russert was recording voiceovers when he collapsed. Previously diagnosed with asymptomatic coronary artery disease. Dr. Michael Newman (Russerts physician) said his disease was well-controlled with medication and exercise, and he had performed well on a stress test.

Cardiac Stress Tests Limitations: Requires a high level of blockage in one or more coronary arteries for abnormal result. Most heart attacks occur in vessels without significant blockage, or stenosis. What is the solution? Or, is there any?

When asked if he thought he could have done more, Dr. Newman replied You know, as physicians, we always hope that we can change people's lives, that we can make them feel better, live longer, that we can intervene, and that's what our role is. Unfortunately, in many instances, our hopes are not fulfilled. Absolutely, I wish Tim was alive and with us today.... And... patients die of heart disease or cancer; we all struggle with the fact there are limits to what we can do. Dr. Newman on The Larry King Show

Definitions of Different Types of Prevention Primordial Prevention: Prevention of coronary heart disease risk factors Primary Prevention: Modification of risk factors in order to prevent or delay the onset of coronary heart disease Secondary Prevention: Initiation of therapy to reduce recurrent coronary heart disease events and decrease cardiac mortality in patients with established coronary heart disease.

Advances in CVD Risk Reduction Not Enough CVD is the leading cause of death in the United States, despite guideline driven care. 1 CVD accounts for 33% of all deaths. 2 Total CVD healthcare costs are projected to rise from $313 billion in 2009 to $1.48 trillion in 2030. 2 50% of people who have had a heart attack have normal cholesterol. 3 2014 Boston Heart Diagnostics Corporation 7 1.Roger et al. Circulation. 2011;123(4):e18-e209. 2.Go AS, Mozaffarian D, Roger VL, et al. Circulation. 2013;127:e2-e245. 3.Sachdeva et al. Am Heart J. 2009;157(1):111-117.e2.

Smoking 1964 1st Surgeon General s report linking smoking with heart disease, lung cancer, and emphysema marked decrease Diet 1968 The US food industry replaces lard and tallow in many foods with vegetable oil beneficial effects on LDL-C and CHD risk. High Blood Pressure - 1972 National High Blood Pressure Education Program and Treatment Guidelines - blood pressure control (JNC 7, get systolic < 130 mmHg, major reduction in CVD, especially stroke) Cholesterol - 1988 National Cholesterol Education Program Adult Treatment Panel Guidelines (latest 2004) get LDL-C < 100, CVD < 70 Diabetes - 1993 Diabetes Control and Complication Trial 2013 guidelines for the diagnosis and treatment of diabetes get HbAIc < 7%. Age Adjusted CVD Rates have dropped by > 50% since 1964 Emerging Targets sdLDL, HDL Particles, Lipoprotein(a), and CRP Major Risk Factors for Cardiovascular Disease

Single most preventable cause of death in the U.S Single most preventable cause of death in the U.S Causes plaque to form in blood vessels Causes plaque to form in blood vessels Reduces HDL (good) cholesterol Reduces HDL (good) cholesterol May cause irregular heart rhythms that could lead to cardiac arrest May cause irregular heart rhythms that could lead to cardiac arrest Puts women who smoke at a much higher risk of developing cardiovascular disease Puts women who smoke at a much higher risk of developing cardiovascular disease Good News: quitting begins to reduce cardiovascular risk immediately Good News: quitting begins to reduce cardiovascular risk immediately Smoking and Heart Disease

2000 Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010 (*BMI 30, or about 30 lbs. overweight for 54 person) 2010 1990 No Data 7.5% (should receive low intensity statin). Use the risk calculator at www.myamericanheart.org/cvrisk calculator (gender, age, sys. Bp, smoking, diabetes, total cholesterol, and HDL cholesterol) Goff DC Jr et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Nov 12.

Definitions of Statin Intensity High: atorvastatin 40 - 80 mg/day, rosuvastatin 20 - 40 mg/day; Moderate: atorvastatin 10 - 20 mg/day, rosuvastatin 5 - 10 mg/day, simvastatin 20 - 40 mg/day, pravastatin 40 mg/day, lovastatin 40 mg/day, fluvastatin XL 80 mg/day, or pitavastatin 2 - 4 mg/day; Low: simvastatin 10 mg/day, pravastatin 10 - 20 mg/day, lovastatin 20 mg/day, fluvastatin XL 20 - 40 mg/day, or pitavastatin 1 mg/day. Stone NJ et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Nov 12.

Use of Non-Statin Agents Clinicians treating high risk patients who have a less than anticipated responses to statins, who are unable to tolerate a less than recommended intensity of a statin, or who are completely statin intolerant, may consider the addition of a nonstatin cholesterol lowering drug. Clinicians should preferentially prescribe drugs that have been shown in randomized clinical trials to provide ASCVD risk reduction benefits that outweigh the potential for adverse effects and drug-drug interactions. Fibrates, niacin, resins, and the statin/ezetimibe combination have shown ASCVD risk reduction in randomized trials as compared to placebo.

In 3-year follow-up in 3,414 patients with CVD and HDL-C < 40 mg/dL combined niacin + LDL-C lowering therapy did not reduce CV events compared with LDL-C-lowering therapy alone. In a subset of patients in the top TG tertile ( 198 mg/dl) and the bottom HDL-C tertile (< 33 mg/dl), ER niacin showed a trend toward benefit (hazard ratio: 0.74, p = 0.073). On-trial LDL-C levels, non-HDL-C levels, and the total cholesterol/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin These data suggest that the high TG/low HDL group are highest risk, and may get benefit from niacin on top of statin therapy. Guyton J et al J Am Col2013; 62:1580-4. AIM HIGH-Post HOC Analysis

In ACCORD Lipid overall event rate was 11.3% in the simvastatin monotherapy group and 10.5% in the simvastatin/ fenofibrate group (p=0.32). In the subgroup with TG > 200 mg/dL and HDL-C < 35 mg/dL event rate was 17.3% (+53%) in the simvastatin monotherapy group and 12.4% (-28%) in the simvastatin/ fenofibrate group (p=0.03). Similar observations in BIP and FIELD Fibrates Fibrates: Subgroup Analysis Ginsberg HN et al New Engl J Med 2010;362:1563-9

Secondary Causes of Dyslipidemia Secondary Causes of Elevated LDL-C: obesity, increased intake saturated fat & trans fats, hypothyroidism, diuretics, cyclosporin, glucocorticoids, amiodorone, biliary obstruction, nephrotic syndrome, pregnancy, & anorexia Secondary Causes of Elevated Triglycerides: obesity, diabetes, high sugar intake, excessive alcohol intake, hypothyroidism, oral estrogens, glucocorticoids, bile acid sequestrants, protease inhibitors, retinoic acid, anabolic steroids, sirolimus, raloxifene, tamoxifen, beta blockers (except carvedilol), thiazides, and pregnancy.

Chylomicron Remnants Particle Density, g/mL Chylomicron 1.20 1.10 1.06 1.02 1.006 0.95 510204060801000 VLDL IDL LDL HDL 2 HDL 3 Particle Size - Diameter, nm VLDL Remnants Lp(a) VLDL Cholesterol-Carrying Lipoproteins Chylomicron Heart disease patients often have increased remnants lipoproteins, small dense LDL), and Lp(a), and decreased large HDL) Genest et al Circulation 1992;85:2025, Campos et al, ATVB 1992; 12:187, Schaefer et al JAMA 1994;59:32, McNamara et al Atherosclerosis 2001;154:229, Asztalos et al ATVB 2004;24:2181, & Ai et al Clin Chem 2010; 56:967-76.

IVUS detects angiographically silent atheroma to get regression LDL-C needs to be 8% - only 2/3 get regression with aggressive statin treatment IVUS = intravascular ultrasound, Nissen S, Yock P. Circulation 2001; 103: 604616, Nicholls S et al ASTEROID and SATURN Studies 2007, 2011. Angiogram IVUS Little evidence of disease Atheroma No evidence of disease IVUS

Statin Meta Analyses Oxford For every 40 mg/dL reduction in LDL-C, there is a 20% reduction in cardiovascular endpoints.

Everyday in the U.S. 1 Every 17 seconds, someone in the U.S. is diagnosed with diabetes 2 Diabetes now kills more people each year than breast cancer and AIDS combined. 2 1. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf (Accessed March 2011) 2. http://www.cdc.gov/media/pressrel/2010/r101022.html (Accessed September 2011) 5200 People are diagnosed with type 2 diabetes People go blind>55 People begin dialysis>120 People undergo amputations>230

Positive Effects of Lifestyle Changes Diabetes Prevention Project 3234 prediabetic subjects with fasting glucose (100 125 mg/dL) and body mass index of 34.0 kg/m 2 Lifestyle modification over 3 years: (goal of 7% weight-loss and > 150 min. physical activity /week, fat < 25% of calories, 500 calorie deficit/day vs. metformin vs. placebo New Development of Diabetes Mellitus 33% over 3 years in usual care group 23% over 3 years in metformin group (-31%) 14% over 3 years in lifestyle group (-58%) Boston Heart Diagnostics - similar lifestyle program Diabetes Prevention Program Research Group. New Eng J Med 2002; 346:393-9.

9 1.Diabetes Prevention Program Research Group. NEJM. 2002; 346:393-403. 2. Tuomilehto J, et al. NEJM. 2001; 344:1343-1350. 3. DREAM Trial Investigators. Lancet. 2006; 368:1096-1105. 4. Zinman B, et al. Lancet. 2010; 376: 103-111. 5. DeFronzo R, et al. N Engl J Med. 2011; 365:182-184 Clinical Studies Demonstrate Prevention is Possible *Currently, no medications are FDA-approved for the prevention of diabetes

CARDIOMETABOLIC IMPACT Lancet 1999 ; 354:617-621 DECODE Study Group 10-year follow-up of Normal Glucose Tolerance, Impaired Glucose Tolerance and Diabetes Mellitus Two-fold increase risk of CVD for IGT vs. NGT Four-fold increase risk of CVD for DM vs. NGT 80% of diabetics die of CVD MI (60%) / CVA (20%)

CARDIOMETABOLIC IMPACT More than 70% of Coronary Artery Disease/Acute Coronary Syndrome sufferers are insulin resistant! Diabetes Care 2008; 31:1955-1959 Lancet 2007; 370:667-675 Every 18mg/dl above 140mg/dl at 2-hour plasma glucose increases cardiovascular and all-cause death rates by 26% over 6-7 years Diabetes Care 2009; 32:1721-1726

LAB CLUES Triglyceride/HDL Ratio (Ethnic variation) GGTP >21mg/dl women; >47mg/dl men ALT > 20mg/dl women > 34mg/dl men Triglycerides >130 mg/dl Low HDL/LOW HDL2b High sdLDL FPG>88mg/dl Fasting Insulin > 16microU/ml HgB A1C > 5.6% ^ MACR ^ hsCRP ^ Fibrinogen ^ Lp-PLA2 Decreased Vitamin D

Examples of Coronary Artery Scans NO CALCIFICATION zero score MODERATE CALCIFICATION SIGNIFICANT CALCIFICATION high score

Primary Prevention of Cardiovascular Disease For persons aged 50 years or older without symptomatic cardiovascular disease, we suggest low-dose aspirin 75 to 100 mg daily over no aspirin therapy (Grade 2B). Remarks: Aspirin slightly reduces total mortality regardless of cardiovascular risk profile if taken over 10 years. In people at moderate to high risk of cardiovascular events, the reduction in myocardial infarction (MI) is closely balanced with an increase in major bleeds. Whatever their risk status, people who are averse to taking medication over a prolonged time period for very small benefits will be disinclined to use aspirin for primary prophylaxis. Individuals who value preventing an MI substantially higher than avoiding a GI bleed will be, if they are in the moderate or high cardiovascular risk group, more likely to choose aspirin.

Aspirin Evidence: Dose and Efficacy 0.51.01.52.0 500-1500 mg34 19 160-325 mg19 26 75-150 mg12 32

Aspirin (81 mg daily or 100 mg every other day) in at risk women >65 years of age Aspirin in at risk women

Aspirin (75-162 mg daily) in those at intermediate risk (10 year risk of CHD >10%) Primary Prevention (Men*) CHD=Coronary heart disease *Specific guideline recommendations for men do not exist, but these guidelines are based on previous general (not gender specific) primary prevention guidelines

Secondary Prevention

CVD Risk Prediction The best predictor of future CHD is the presence of pre-existing disease. There is a high correlation between carotid and coronary artery atherosclerosis. Carotid ultrasound remains the most cost-effective strategy to detect the presence of early atherosclerosis. Another option is cardiac calcium scoring.

Date of download: 11/2/2014 Copyright 2014 American Medical Association. All rights reserved. Effect of Smoking Cessation on Mortality After Myocardial Infarction: Meta-analysis of Cohort Studies Arch Intern Med. 2000;160(7):939-944. doi:10.1001/archinte.160.7.939 Benefit of Smoking Cessation on Mortality After Myocardial Infarction: Results of the Primary Studies* Table Title:

Aspirin Recommendations (Contd) Aspirin (75-162 mg daily) if known CHD/ASVD Aspirin (162-325 mg daily) for at least 3 months after sirolimus-eluting stent implantation and at least 6 months after paclitaxel-eluting stent implantation after which aspirin (75-162 mg daily) should be continued indefinitely Secondary Prevention ASVD=Atherosclerotic vascular disease, CABG=Coronary artery bypass graft, CHD=Coronary heart disease

Aspirin Recommendations (Contd) Aspirin (75-162 mg daily) as the initial dose after stent implantation in those at higher bleeding risk Aspirin (100-325 mg daily) following CABG surgery* Secondary Prevention *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

Clopidogrel (75 mg daily; Class I, Level B), prasugrel* (10 mg daily; Class I, Level C), or ticagrelor (90 mg twice daily; Class I, Level C) if aspirin intolerance or a true aspirin allergy following a NSTE-ACS Clopidogrel (75 mg daily) or ticagrelor (90 mg twice daily) in addition to aspirin for up to 1 year following a NSTE-ACS managed conservatively NSTE-ACS=Non ST-segment elevation acute coronary syndrome; PCI=Percutaneous coronary intervention, STEMI=ST-segment elevation myocardial infarction Source: Jneid H et al. JACC 2012;60:645-681 I IIaIIbIII P2Y 12 Receptor Antagonist Recommendations Secondary Prevention I IIaIIbIII I IIaIIbIII *In PCI treated patients

Clopidogrel (75 mg daily), prasugrel (10 mg daily), or ticagrelor (90 mg twice daily) in addition to aspirin for 1 year following PCI for a NSTE-ACS or a STEMI Clopidogrel (75 mg daily) in addition to aspirin for a minimum of 14 days (Class I, Level A) and up to 1 year (Class I, Level C) following fibrinolytic therapy for a STEMI NSTE-ACS=Non ST-segment elevation acute coronary syndrome; PCI=Percutaneous coronary intervention, STEMI=ST-segment elevation myocardial infarction Sources: Jneid H et al. JACC 2012;60:645-681 OGara PT et al. JACC 2013;61:e78-e140 P2Y 12 Receptor Antagonist Recommendations Secondary Prevention I IIaIIbIII I IIaIIbIII I IIaIIbIII

If the risk of morbidity because of bleeding outweighs the anticipated benefit afforded by a P2Y 12 receptor antagonist, earlier discontinuation should be considered Continuation of a P2Y 12 receptor antagonist beyond 1 year may be considered in patients undergoing drug eluting stent placement I IIaIIbIII P2Y 12 Receptor Antagonist Recommendations (Contd) Secondary Prevention I IIaIIbIII Sources: Kushner F et al. JACC 2009;54:2205-2241 Jneid H et al. JACC 2012;60:645-681 OGara PT et al. JACC 2013;61:e78-e140

An ACE inhibitor should be started and continued indefinitely in all patients with left ventricular ejection fraction 16 microU/ml 57% 85% Ann Int Med 2003; 139:802 McLaughlin et al. POOR MANS TEST TRIGLYCERIDE/HDL RATIO PRESENT ON EVERY LIPID PROFILE CAUCASIAN >3.5 MEXICAN-AMERICAN >3.0 NON-HISPANIC BLACK >2.0

DART TRIAL In the Diet and Reinfarction Trial (DART) in 2033 men with CHD increased intake of fish or use of 2 fish oil caps/day (provided) reduced CHD mortality 29% over 2 years No benefit from other diet interventions in this trial including restriction of total fat and animal fat Burr et al Lancet 2;757-761,1989

Schaefer E J et al. JAMA 1994;271:99-1003. Genest JJ, Jr. et al. Circulation 1992;85:2025-33. Clarke R et al. N Engl J Med 2009;361:2518-28 Ballantyne CM (Ed.). 2009. Clinical Lipidology. Philadelphia: Saunders, (pg.130). Lipoprotein (a) [Lp(a)] Lp(a) is a plasma lipoprotein that is composed of two parts LDL-like particle Apolipoprotein (a) [apo(a)] protein that is made in the liver and is attached to the apoB portion of this particle Low risk 30 mg/dL Elevated levels are an independent risk factor for Myocardial infarction Coronary artery disease Cerebral vascular disease Vein graft stenosis Retinal artery occlusion Lipoprotein(a) Definition & Clinical Significance

JELIS TRIAL In JELIS (Japanese EPA Lipid Intervention Study) 18,645 hypercholesterolemic subjects (>6.5 mmol/L or 250 mg/dl off medication) randomized to 1800 mg/day of EPA versus placebo all patients were placed on pravastatin 20 mg/day at onset 4.7 yr. followup. Major coronary events (fatal MI, MI, angioplasty, bypass) and were reduced by 19% (p=0.01). No effect on sudden death, No effect on lipids, except that statin lowered LDL C 25% in both groups* - particular benefit noted in group with TG > 150 mg/dL and HDL-C 150 ul/mL).** Subanalysis of JELIS indicated no risk reduction for stroke (1.3% vs. 1.5% in placebo), but significant reduction in recurrent stroke from 10.5% in placebo to 6.8%, 20% reduction (p=0.01).*** *Yokohama et al Lancet 2007; 369:1090-1098, **Saito et al Atherosclerosis 2008 (epub), ***Tanaka et al Stroke 2008;39:2052-8.

Kwiterovich PO, Jr.(Ed.). 2010. The Johns Hopkins Textbook of Dyslipidemia Philadelphia: Wolters Kluwer, (pp 222-229). Primary goal is to optimize LDL-C, sdLDL-C, and apoB levels Secondary goal is to lower Lp(a) below 20 mg/dL (as of yet not documented by intervention studies) Primary pharmacologic options Niaspan 2,000 mg lowers Lp(a) by a mean of 24% Immediate release (IR) niacin lowers Lp(a) by about 30% Effects of therapy may not be seen for several months Other Lp(a) lowering modalities Estrogen & androgens significantly lower Lp(a) Tamoxifen lowers Lp(a) in post-menopausal women Aspirin 81 mg QD can lower Lp(a) levels slightly LDL apheresis Statins do not lower Lp(a) Diet & exercise have little to no effect on Lp(a) levels Elevated Lipoprotein(a) Treatment Considerations

sdLDL-C and CHD Risk A better marker of CHD risk than LDL-C 2014 Boston Heart Diagnostics Corporation 89 LDL-CsdLDL-C MESA (n = 4,387) 1 Top quartile*>140 mg/dL>50 mg/dL Hazard ratio (P), new CHD 1.75 (0.019)2.41 (0.0037) ARIC (n = 11,419) 2 Top quartile>146 mg/dL>50 mg/dL Hazard ratio (P), new CHD 1.56 (50 mg/dL were predictive of risk even in individuals with LDL-C

CHD Risk Prediction sdLDL > apoB > non-HDL-C > LDL-P > LDL-C 1 Tsai MY et al. Arterioscler Thromb Vasc Biol 2014; 34:196-201. 2 Hoogeveen RC et al. Arterioscler Thromb Vasc Biol 2014; 34:1069-1077 3 Ai M et al. Clin Chem 2010; 56:967-976. 4 Emerging Risk Factors Collaboration. JAMA 2009; 302:1993-2000. sdLDL-Camount of cholesterol in sdLDL particles (LDL d 1.044-1.063 g/mL) apoBconcentration of total apoB in plasma (number of apoB containing/atherogenic particles) Non-HDL-Camount of cholesterol in all apoB containing/atherogenic particles LDL-Pnumber of LDL particles determined by NMR LDL-Camount of cholesterol in all LDL particles (d 1.019-1.063 g/mL)

Calcium Soft plaques

Prevalence of Cardiovascular Disease in the United States Go AS et al. Circulation 2003;127:e6-e245

Calendar Year (1900-2006) Go AS et al. Circulation 2003;127:e6-e245 Rates of Death from Cardiovascular Disease in the United States

Residual Cardiovascular Risk (70%) in Major Statin Trials (Risk Lowered around 30%) 4 HPS Collaborative Group. Lancet. 2002;360:7-22. 5 Shepherd J, et al. N Engl J Med. 1995;333:1301-1307. 6 Downs JR, et al. JAMA. 1998;279:1615-1622. 1 4S Group. Lancet. 1994;344:1383-1389. 2 LIPID Study Group. N Engl J Med. 1998;339:1349-1357. 3 Sacks FM, et al. N Engl J Med. 1996;335:1001-1009. LDL-C N 44444159 20 536 659566059014 -35% -28% -29%-26%-25% Secondary High RiskPrimary Patients Experiencing Major CHD Events, % 4S 1 LIPID 2 CARE 3 HPS 4 WOSCOPS 5 AFCAPS/ TexCAPS 6 19.4 12.3 10.2 8.7 5.5 6.8 28.0 15.9 13.2 11.8 7.9 10.9 CHD events occur in patients treated with statins

JUPITER Primary Trial Endpoint : MI, Stroke, UA/Revascularization, CV Death Placebo 251 / 8901 Rosuvastatin 142 / 8901 HR 0.56, 95% CI 0.46-0.69 P < 0.00001 HR 0.21 if LDL C < 70 mg/dl and CRP < 1.0 mg/L - 44 % 01234 0.00 0.02 0.04 0.06 0.08 Cumulative Incidence Number at Risk Follow-up (years) Rosuvastatin Placebo 8,9018,6318,4126,5403,8931,9581,353983544157 8,9018,6218,3536,5083,8721,9631,333955534174 Ridker et al NEJM 2008

Atherosclerosis TimelineFoamCellsFattyStreakIntermediateLesion Atheroma FibrousPlaqueComplicatedLesion/Rupture Endothelial Dysfunction From first decadeFrom third decade From fourth decade Growth mainly by lipid accumulation Smooth muscle and collagen Thrombosis, hematoma Stary HC, et al. Circulation. 1995;92:1355-74. Artery wall often gets larger with increasing plaque-Glagov NEJM 1987

Optimizing CVD Risk Smoking Cessation use of Chantix if necessary Lifestyle : decrease animal and full fat dairy, trans fats, sugars, and increase essential fats, vegetables, and fruits, and daily exercise High Blood Pressure - goals vary Diabetes - get HbAIc < 7%, lifestyle change is the optimal therapy in overweight or obese insulin resistant patients. LDL-C, sdLDL-C - In CVD and high risk patients reduce LDL-C to < 70 mg/dL and sdLDL-C to < 20 mg/dL with lifestyle, statins, and if necessary ezetimibe HDL-C and ApoA-I in alpha-1 HDL smoking cessation, weight loss, niaicin therapy at 2 grams/day are all ways to increase HDL-C > 50 mg/dL and especially to raise apoA-I in alpha-1 HDL to > 20 mg/dL. Lp(a) optimize all other risk factors, and in CVD patients who also have low HDL-C and alpha-1 HDL consider niacin 2 grams/day

Cumulative incidence of death by number of cardiac rehabilitation sessions attended. Kwan G, and Balady G J Circulation. 2012;125:e369-e373 Copyright American Heart Association, Inc. All rights reserved.

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Preventing Cardiovascular Events Primary and Secondary November 8 th 2014 Slides by Dr Dharmesh Patel and Arie Szatkowski Last Minute Presentation by Dr