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Preventing Cardiovascular Events Primary and Secondary November 8th 2014 Slides by Dr Dharmesh Patel and Arie Szatkowski Last Minute Presentation by Dr Arie Szatkowski NBC’s Tim Russert dies at 58 • Russert was recording voiceovers when he collapsed. • Previously diagnosed with asymptomatic coronary artery disease. Dr. Michael Newman (Russert’s 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 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. 7 © 2014 Boston Heart Diagnostics Corporation Major Risk Factors for Cardiovascular Disease • 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 Smoking and Heart Disease • • • • • • Single most preventable cause of death in the U.S Causes plaque to form in blood vessels Reduces HDL (“good”) cholesterol May cause irregular heart rhythms that could lead to cardiac arrest Puts women who smoke at a much higher risk of developing cardiovascular disease Good News: quitting begins to reduce cardiovascular risk immediately Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010 (*BMI 30, or about 30 lbs. overweight for 5’4” person) 2000 1990 2010 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Obesity in Mississippi • 2nd Fattest state in the country • Over 2/3 of MS adults are overweight • Over 26% are obese • Only 38 % get recommended physical activity • # 1 in heart disease deaths • # 1 in young adults with diabetes • Annual state costs at least $757 million with overweight and obesity Scope of the Problem (Cont’d) Prevalence of CHD associated with 3 projections of adult obesity Population prevalence of CHD Prevalence (%) Number of Excess Cases Excess prevalence of CHD Year Year Extrapolation from current data suggests that overweight adolescents will increase rates of CHD among future young and middle-aged adults CHD=Coronary heart disease Source: Bibbins-Domingo K et al. NEJM 2007;357:2371-2379 2013 American Heart Association/ American College of Cardiology Guidelines • “dietary pattern that emphasizes fruits and vegetables, whole grains, legumes, fish, poultry, nuts and vegetable oils for fat, and restricted consumption of saturated and trans fats, sugar, sodium, and red meat”. • Dietary pattern evocative of the Mediterranean or DASH-type diet J. Am. Coll. Cardiol. 2014 Jan. 28 Mediterranean Diet Study • 7447 men and women in Spain at high CVD risk (age 55-80 years) received either: 1) Mediterranean diet with extra-virgin olive oil (140 ml/day), 2) Mediterranean diet with mixed nuts (30 grams/day of walnuts, almonds, and hazelnuts), or 3) a control diet (advice to reduce dietary fat). • Adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) for M diet group with olive oil and 0.72 (95% CI, 0.54 to 0.96) for the M diet group with nuts, respectively, versus the control group. No diet-related adverse effects were reported. • Primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or CVD death) • Conclusions: “ Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events.” Estruch R et al N Engl J Med. 2013 Apr 4;368(14):1279-90. Associations Between the Percent of Calories Derived from Specific Foods and CHD Mortality in the 20 Countries Study* Food Source Correlation Coefficient† Butter 0.546 All dairy products 0.619 Eggs 0.592 Meats 0.561 Sugar and syrup 0.676 Grains, fruits, and vegetables -0.633 *1973 data, all subjects. From Stamler J: Population studies. In Levy R: Nutrition, Lipids, and CHD. New York, Raven, 1979. †All coefficients are significant at the P<0.05 level. Dietary Recommendations Primary Prevention I IIa IIb III Women should consume a diet rich in fruits and vegetables; choose whole-grain, high-fiber foods; consume fish, especially oily fish,* at least twice a week; limit intake of saturated fat to <10% of energy, and if possible to <7%, cholesterol to <300 mg/d, alcohol intake to no more than 1 drink per day, and sodium intake to <2.3 g/d (approximately 1 tsp salt). Consumption of trans-fatty acids should be as low as possible (eg, <1% of energy) *Pregnant and lactating women should avoid eating fish potentially high in methylmercury Source: Mosca L et al. Circulation 2007;115:1481-1501 2013 AHA/ACC Guideline on Lifestyle • For blood pressure lowering, if recommended goals for sodium are not attainable, reducing sodium intake by at least 1,000 mg/day lowers blood pressure. • A reduction in sodium intake of approximately 1,000 mg/day reduces CVD events by approximately 30%. • Combining the DASH dietary pattern with lower sodium intake is recommended for lowering blood pressure. Exercise Reduces Cardiac Event Recurrence Steffen-Batey et al. Change in level of physical activity and risk of all-cause mortality or reinfarction: The Corpus Christi Heart Project. Circulation. 102(18):2204-9, 2000 Oct 31. Physical Activity: Secondary Prevention Age-adjusted mortality rate/1000 person-years Observational study of self-reported physical activity in 772 men with CHD Physical activity Moderate exercise is associated with reduced mortality CHD=Coronary heart disease, CVD=Cardiovascular disease Source: Wannamethee SG et al. Circulation 2000;102:1358-1363 CV Benefits of Lowering BP Average Percent Reduction • Stroke incidence 35–40% • Myocardial infarction 20–25% • Heart failure 50% 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) Condition mmHg Primary hypertension <140/90 Diabetes mellitus <140/90* Chronic renal disease <140/90* Age > 60 years <150/90* JAMA.Published online December 18, 2013. JNC VIII Guidelines • For younger patients (age, <60), drug therapy should be considered for diastolic BP ≥90 mm Hg or systolic BP ≥140 mm Hg. The goal is <140/90 mm Hg, but only the diastolic thresholds are based on high-quality evidence. • In the general population <60 years, initiate pharmacologic treatment to lower BP at DBP 90mmHg and treat to a goal DBP<90mmHg • In the general population aged 60 years, if pharmacologic treatment for high BP results in lower achieved SBP (eg, <140mmHg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. • For older patients (age, ≥60), drug therapy should be considered for diastolic BP ≥90 mm Hg or systolic BP ≥150 mm Hg; the goal is <150/90 mm Hg. • For patients with diabetes and patients with chronic kidney disease, the threshold to initiate drug therapy is 140/90 mm Hg; the goal is <140/90 mm Hg. JNC VIII Guidelines Cont’d • In nonblack patients, acceptable initial drug-class choices are thiazide-type diuretics, calcium-channel blockers (CCBs), angiotensin-converting–enzyme (ACE) inhibitors, and angiotensinreceptor blocker (ARBs). • In black patients, acceptable initial drug-class choices are thiazidetype diuretics or CCBs. • Patients with chronic kidney disease generally should receive ACE inhibitors or ARBs. • When patients require escalation of therapy, either maximizing doses of individual drugs sequentially or combining several drugs at submaximal doses is acceptable. Do not use ACE inhibitors and ARBs together. Changes compared to JNC VII Guidelines • JNC 7 recommended a treatment threshold of 140/90 mm Hg regardless of age, whereas JNC 8 raises the systolic threshold at age 60. • In addition, JNC 7 recommended a lower treatment threshold (130/80 mm Hg) for patients with diabetes or chronic kidney disease, but JNC 8 does not. • In JNC 7, thiazide-type diuretics were recommended as initial drug therapy (unless compelling reasons dictated another drug class), with CCBs, ACE inhibitors, ARBs, and β-blockers as alternates. In JNC 8, the initial drug choice is broadened to four classes for nonblack patients and two classes for black patients. • β-blockers are no longer recommended for initial therapy because they might afford less protection against stroke. On-Treatment LDL-C is Closely Related to CHD Events in Statin Trials – Lower is Better 30 4S - Placebo 25 Rx - Statin therapy PRA – pravastatin ATV - atorvastatin 20 Secondary Prevention 4S - Rx LIPID - Placebo 15 10 5 TNT – ATV80 PROVE-IT – ATV LIPID - Rx CARE - Rx HPS - Rx TNT – ATV10 PROVE-IT - PRA 0 60 (1.6) Primary Prevention HPS - Placebo WOSCOPS – Placebo AFCAPS - Placebo But, how low should we go? 40 (1.0) CARE - Placebo 80 (2.1) AFCAPS - Rx 6 WOSCOPS - Rx ASCOT - Placebo ASCOT - Rx 100 (2.6) 120 (3.1) LDL-C achieved mg/dL (mmol/L) 140 (3.6) 160 (4.1) Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279 LaRosa JC et al. N Engl J Med 2005;352:e-version 180 (4.7) 200 (5.2) Majority of Residual Risk for Cardiovascular Events Remains Despite LDL Lowering Therapy Reduction in Major Coronary Events (%) 0 100 [-20] -38% -25% -25% -27% -31% -38% 62% 75% 75% 73% 69% 62% 4S LIPID CARE HPS WOSCOPS AFCAPS/TexCAPS 4,444 9,014 4,159 20,536 6,595 6,605 80 [-40] 60 Residual Major Coronary Events (%) [-60] 40 [-80] 20 [-100] 0 Trial N Secondary Prevention High Risk Primary Prevention Adapted from Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005;46(7):1225-1228. 26 © 2014 Boston Heart Diagnostics Corporation Groups Recommended for Statin Therapy • Group 1: Subject with evidence of clinical CVD (acute coronary syndrome, history of myocardial infarction, stable or unstable angina, coronary or other revascularization, stroke, transient ischemic attacks, and/or peripheral vascular disease. (should receive high intensity statin and ideally get more 50% LDL-C reduction) • Group 2: Subject with LDL-C > 190 mg/dL. (should receive high intensity statin) • Group 3: Diabetic subject age 40 - 75 years with LDL-C of 70 - 189 mg/dL and without CVD. (should receive moderate intensity statin, and get 30 50% LDL-C reduction) • Group 4: Subject without ASCVD or diabetes and a 10 year ASCVD risk >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.” AIM HIGH-Post HOC Analysis 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. Fibrates: Subgroup Analysis Fibrates • 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 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. Cholesterol-Carrying Lipoproteins VLDL 0.95 VLDL Remnants Particle Density, g/mL 1.006 Chylomicron Chylomicron VLDL VLDL IDL Chylomicron Remnants 1.02 LDL 1.06 1.10 HDL2 Lp(a) HDL3 Heart disease patients often have increased remnants lipoproteins, small dense LDL), and Lp(a), and decreased large HDL) 1.20 5 10 20 40 60 Particle Size - Diameter, nm 80 1000 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 < 70 mg/dL and HDL-C needs to be raised by > 8% - only 2/3 get regression with aggressive statin treatment IVUS Angiogram No evidence of disease Little evidence of disease IVUS Atheroma IVUS = intravascular ultrasound, Nissen S, Yock P. Circulation 2001; 103: 604–616, Nicholls S et al ASTEROID and SATURN Studies 2007, 2011. 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 >55 5200 People are diagnosed with type 2 diabetes Every 17 seconds, someone in the U.S. is diagnosed with diabetes2 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) People go blind >120 People begin dialysis >230 People undergo amputations Diabetes now kills more people each year than breast cancer and AIDS combined.2 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/m2 • 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. Clinical Studies Demonstrate Prevention is Possible *Currently, no medications are FDA-approved for the prevention of diabetes 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 9 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 • Triglycerides >130 mg/dl • Low HDL/LOW HDL2b • High sdLDL • FPG>88mg/dl • Fasting Insulin – >16microU/ml • Triglyceride/HDL Ratio (Ethnic variation) • • GGTP >21mg/dl women; ALT • HgB A1C > 5.6% • ^ MACR >47mg/dl men • ^ hsCRP > 20mg/dl women • ^ Fibrinogen > 34mg/dl men • ^ Lp-PLA2 • Decreased Vitamin D Examples of Coronary Artery Scans NO CALCIFICATION “zero score” MODERATE SIGNIFICANT CALCIFICATION 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 Indirect comparisons of aspirin doses on vascular events in high-risk patients 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 0 Odds Ratio for Vascular Events P<.000 1 1.5 2.0 0.5 1.0 Antiplatelet Better Antiplatelet Worse Antithrombotic Trialist Collaboration. BMJ 2002;324:71-86 Aspirin Primary Recommendations Prevention (Women) I IIa IIb III Aspirin (81 mg daily or 100 mg every other day) in at risk women >65 years of age I IIa IIb III Aspirin in at risk women <65 years of age for ischemic stroke prevention I IIa IIb III Aspirin in optimal risk women <65 years of age CHD=Coronary heart disease Aspirin Recommendations Primary Prevention (Men*) I IIa IIb III Aspirin (75-162 mg daily) in those at intermediate risk (10 year risk of CHD >10%) *Specific guideline recommendations for men do not exist, but these guidelines are based on previous general (not gender specific) primary prevention guidelines CHD=Coronary heart disease 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. 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 Table Title: Benefit of Smoking Cessation on Mortality After Myocardial Infarction: Results of the Primary Studies* Date of download: 11/2/2014 Copyright © 2014 American Medical Association. All rights reserved. Aspirin Recommendations (Cont’d) Secondary Prevention I IIa IIb III Aspirin (75-162 mg daily) if known CHD/ASVD I IIa IIb III 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 ASVD=Atherosclerotic vascular disease, CABG=Coronary artery bypass graft, CHD=Coronary heart disease Aspirin Recommendations (Cont’d) Secondary Prevention I IIa IIb III Aspirin (75-162 mg daily) as the initial dose after stent implantation in those at higher bleeding risk I IIa IIb III Aspirin (100-325 mg daily) following CABG surgery* *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 P2Y12 Receptor Antagonist Recommendations I IIa IIb III I IIa IIb III I IIa IIb III Secondary Prevention 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 *In PCI treated patients 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 P2Y12 Receptor Antagonist Recommendations Secondary Prevention I IIa IIb III 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‡ I IIa IIb III I IIa IIb III 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: H et al. JACC 2012;60:645-681 ‡O’Gara PT et al. JACC 2013;61:e78-e140 †Jneid P2Y12 Receptor Antagonist Recommendations (Cont’d) Secondary Prevention I IIa IIb III If the risk of morbidity because of bleeding outweighs the anticipated benefit afforded by a P2Y12 receptor antagonist, earlier discontinuation should be considered I IIa IIb III Continuation of a P2Y12 receptor antagonist beyond 1 year may be considered in patients undergoing drug eluting stent placement Sources: Kushner F et al. JACC 2009;54:2205-2241 Jneid H et al. JACC 2012;60:645-681 O’Gara PT et al. JACC 2013;61:e78-e140 ACE Inhibitor Recommendations Secondary Prevention I IIa IIb III An ACE inhibitor should be started and continued indefinitely in all patients with left ventricular ejection fraction <40% and in those with hypertension, DM, or CKD, unless contraindicated I IIa IIb III An ACE inhibitor in all other patients ACE=Angiotensin converting enzyme, CKD=Chronic kidney disease, DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 Angiotensin Receptor Blocker Recommendations Secondary Prevention I IIa IIb III An ARB in patients who have HF or who have had a MI with left ventricular ejection fraction <40% and who are ACE-inhibitor intolerant I IIa IIb III An ARB in other patients who are intolerant of an ACE inhibitor I IIa IIb III Use of an ARB in combination with an ACE inhibitor is not well established in those with systolic heart failure ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, HF=Heart failure, MI=Myocardial infarction Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 Beta-Blocker Recommendations Secondary Prevention I IIa IIb III Beta-blocker should be used in all patients with LVSD (ejection fraction <40%) with HF or prior MI, unless contraindicated*. (Use should be limited to carvedilol, metoprolol succinate, or bisoprolol, which have been shown to reduce mortality.) I IIa IIb III Beta-blocker for 3 years in all patients with normal left ventricular function who have had a MI or ACS I IIa IIb III Beta-blocker beyond 3 years as chronic therapy in all patients with normal left ventricular function who have had a MI or ACS *Relative contraindications include asthma, chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds ACS=Acute coronary syndrome, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 Cardiac Rehabilitation: Greater Benefit with Greater Attendance Death (%) Myocardial infarction (%) Observational study of 30,161 Medicare patients attending at least 1 phase II cardiac rehabilitation session Years after Index Date Years after Index Date There is a strong dose-response relationship between the number of cardiac rehabilitation sessions attended and long-term CV outcomes CV=Cardiovascular Source: Hammill BG et al. Circulation 2010;121:63-70 What Diagnoses are Covered? • Medicare Guidelines: 36 sessions per year after cardiac event − Angina − Myocardial Infarction − Coronary Artery Bypass Graft − Heart Transplant − Valve Surgery − Stent − Coronary Artery Disease (CAD) • Private insurance coverage may vary and may cover - PAD - CHF - Cardiomyopathy - Valvular disease Utilization Benefits: • Reduced risk of fatal MI (<25%) • Decreased severity of angina & need for antiangina meds • Decreased hospitalizations • Decreased cost of physician office visits & hospitalizations (<35%) • Fewer ER visits Patient Benefits: • Improved functional capacity • Increased knowledge of heart disease • Improved adherence to positive lifestyle changes • Better compliance with medical regime • Increased self-esteem and confidence • Reduced subsequent morbidity & mortality r/t CAD Lifestyle Benefits: Risk Factor and Lifestyle Modification • Smoking cessation • Lipid improvement • Blood pressure control • Exercise guidance • Weight management • Diabetes control • Stress management Antioxidant Vitamin Guidelines Secondary Prevention I IIa IIb III Antioxidant vitamin supplements (e.g., vitamins E, C, or beta carotene) should not be used for secondary prevention in NSTE-ACS. NSTE-ACS=Non-ST-segment elevation acute coronary syndrome Anderson JL et al. JACC 2007;50:652-726 B Vitamins and Folic Acid Guidelines I IIa IIb III Secondary Prevention Folic acid, with or without B6 and B12, should not be used for secondary prevention in NSTE-ACS NSTE-ACS=Non-ST-segment elevation acute coronary syndrome Anderson JL et al. JACC 2007;50:652-726 Hormone Replacement Therapy Guidelines Secondary Prevention I IIa IIb III I IIa IIb III HRT with estrogen plus progestin, or estrogen alone, should not be given de novo to postmenopausal women after NSTE-ACS for secondary prevention of coronary events. Postmenopausal women who are already taking estrogen plus progestin, or estrogen alone, at the time of NSTE-ACS in general should not continue HRT. Women who are more than 1-2 years past the initiation of HRT who wish to continue therapy for another compelling indication should weigh the risks and benefits, recognizing the greater risk of CV events and breast cancer (combination therapy) or stroke (estrogen). CV=Cardiovascular, HRT=Hormone replacement therapy, NSTEACS=Non-ST-segment elevation acute coronary syndrome Anderson JL et al. JACC 2007;50:652-726 Nonsteroidal Anti-inflammatory Drug Guidelines Secondary Prevention I IIa IIb III I IIa IIb III At hospital discharge, the patient’s need for treatment of chronic musculoskeletal discomfort should be assessed, and a stepped-care approach to treatment should be used, starting with acetaminophen, small doses of narcotics, or nonacetylated salicylates. It is reasonable to use nonselective NSAIDs, such as naproxen, if initial therapy with acetaminophen, small doses of narcotics, or nonacetylated salicylates is insufficient. NSAIDs=Nonsteroidal anti-inflammatory drugs Anderson JL et al. JACC 2007;50:652-726 Nonsteroidal Anti-inflammatory Drug Guidelines (Cont’d) Secondary Prevention I IIa IIb III It is reasonable to use nonselective NSAIDs, NSAIDs with increasing degrees of relative COX-2 selectivity may be considered for pain relief only for situations in which intolerable discomfort persists despite attempts at steppedcare therapy with acetaminophen, small doses of narcotics, nonacetylated salicylates, or nonselective NSAIDs. In all cases, the lowest effective doses should be used for the shortest possible time COX-2-Cyclooxygenase 2, NSAIDs=Nonsteroidal anti-inflammatory drugs Anderson JL et al. JACC 2007;50:652-726 Aldosterone Antagonist Guidelines Secondary Prevention I IIa IIb III Use of aldosterone blockade in post-MI patients without significant renal dysfunction* or hyperkalemia** is recommended in patients who are already receiving therapeutic doses of an ACE inhibitor and beta-blocker, who have a LV EF <40%, and who have either DM or HF *Estimated creatinine clearance should be >30 ml/min **Potassium should be <5.0 mEq/L ACE=Angiotensin converting enzyme, DM=Diabetes mellitus, EF=Ejection fraction, HF=Heart failure, LV=Left ventricular, MI=Myocardial infarction Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 Digoxin Guidelines I IIa IIb III Secondary Prevention Digoxin in those with symptomatic HF and LVSD (EF <45%) to reduce hospitalizations for HF* I IIa IIb III Digoxin in those with asymptomatic LVSD and normal sinus rhythm *Contraindications include significant sinus or atrioventricular block unless a permanent pacemaker is present EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic function Source: Hunt SA et al. Circulation 2005;112:e154-235 Implantable Cardioverter Defibrillator Guidelines Secondary Prevention I IIa IIb III Patients with an ejection fraction of <35% who are at least 40 days post-MI and are in NYHA functional Class II or III Patients with an ejection fraction of <30% who are at least 40 days post-MI and are in NYHA functional Class I I IIa IIb III Patients with nonsustained VT due to prior MI, an ejection fraction of <40%, and inducible sustained VT or VF at EP study EP=Electrophysiology, MI=Myocardial infarction, NYHA=New York Heart Association, VF=Ventricular fibrillation, VT=Ventricular tachycardia Epstein AE et al. Circulation 2008;117:e350-408 Influenza Vaccination Guidelines I IIa IIb III Secondary Prevention Patients with cardiovascular disease should have an annual influenza vaccination Source: Smith Jr SC et al. JACC 2011;58:2432-2446 Evidence for Current Cardiovascular Disease Prevention Guidelines Room for Improvement Utilization of Risk Reducing Medications at Discharge in Acute Coronary Syndromes ACTION Registry/Get With The Guidelines (GWTG) Data 86% NSTEMI STEMI NSTEMI=Non-ST-segment elevation myocardial infarction, STEMI=ST-segment elevation myocardial infarction Source: ACTION Registry-GWTG DATA: January 1, 2010 – December 31, 2010. Courtesy of NCDR 10/21/2011 Strategies for Initiating and Optimizing Cardiovascular Therapies Hospital based performance improvement systems In-hospital initiation of CV protective therapies Pay for performance/financial incentives Nurse or pharmacist managed outpatient CV prevention programs Preventive cardiology and cardiac rehabilitation centers Virtual prevention clinics using electronic medical record systems Combination of CV protective medications CV=Cardiovascular Thank You