Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Cardiac contractility modulation wikipedia , lookup
Remote ischemic conditioning wikipedia , lookup
Saturated fat and cardiovascular disease wikipedia , lookup
Cardiovascular disease wikipedia , lookup
Coronary artery disease wikipedia , lookup
Quantium Medical Cardiac Output wikipedia , lookup
1 Understanding and Applying Cardiovascular Treatment Guidelines Gregg C. Fonarow, MD, FACC, FAHA Eliot Corday Professor of CV Medicine and Science UCLA Division of Cardiology David Geffen School of Medicine, UCLA Director, Ahmanson-UCLA Cardiomyopathy Center Co-Chief, UCLA Division of Cardiology Los Angeles, California 2 Presenter and Program Disclosure Information Gregg C. Fonarow, MD FINANCIAL DISCLOSURE: Consultant, Honorarium: Medtronic, Novartis UNLABELED/UNAPPROVED USES DISCLOSURE: None 3 Burden of Atherosclerotic Vascular Disease: CAD, CVD, PVD • Prevalence– 25 million in United States • Annual rates Myocardial infarction–1.2 million Strokes-795,000 CVD Mortality–814,000 (every 30 seconds a death) Cardiac catheterization–1.1 million Percutaneous revascularization–622,00 Surgical revascularization–232,000 • Annual direct cost–>$280 billion American Heart Association. 2011 Heart and Stroke Statistical Update. At: http://www.americanheart.org. 4 Cardiovascular Disease Remains the Leading Killer of Men and Women Deaths per 100,000 Population (log scale) Death Rates for Leading Causes of Death for All Ages (US, 1950-2002) 1000 Heart disease Cancer Stroke 100 Unintentional injuries Chronic lower respiratory disease 10 1950 1960 1970 1980 1985 1990 1995 2002 Year Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/nchs/ppt/hus/HUS2004Chartbk.ppt#280,25,Slide25. Accessed July 11, 2005. 5 Potential Therapies for Atherosclerosis Folate Stents Olive Oil Calcium Channel Blockers Nitrates Iron Chelation Fish Oils Phlebotomy Vitamin B12 Red Wine Estrogen Fibrates Anti-Oxidants Alcohol Walnuts Meditation Beta Blockers Niacin Lasers Fiber ? Statins Garlic ACE Inhibitors Weight Loss Vitamin E Calcium Chelation Aspirin Glucose Control Coumadin Exercise L-Arginine Soy Beans Platelet antagonists Acupuncture Blood Pressure Control Oat Bran Vitamin C Resins Biofeedback Beta Carotene Thyroid Hormones Vegetables Gene Therapy Diet 6 AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update Sidney C. Smith, JR, MD, FAHA, FACC, Chair; Emelia J. Benjamin, MD, ScM, FAHA, FACC; Robert O. Bonow, MD, FAHA, FACC; Lynne T. Braun, PhD, ANP, FAHA; Mark A. Creager, MD, FAHA, FACC; Barry A. Franklin, PhD, FAHA; Raymond J. Gibbons, MD, FAHA, FACC; Scott M. Grundy, MD, PhD, FAHA; Loren F. Hiratzka, MD, FAHA, FACC; Daniel W. Jones, MD, FAHA; Donald M. Lloyd-Jones, MD, ScM, FAHA, FACC; Margo Minissian, ACNP, AACC, FAHA; Lori Mosca, MD, PhD, MPH, FAHA; Eric D. Peterson, MD, MPH, FAHA, FACC; Ralph L. Sacco, MD, MS, FAHA; John Spertus, MD, MPH, FAHA, FACC; James H. Stein, MD, FAHA, FACC; Kathryn A. Taubert, PhD, FAHA J Am Coll Cardiol 2011:58:2432–46 7 Secondary Prevention Guidelines • Since the 2006 update of the AHA/ACC consensus statement on secondary prevention, important evidence from clinical trials has emerged that further supports and broadens the merits of aggressive risk reduction therapies • This growing body of evidence confirms that aggressive comprehensive risk factor management improves survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life • The secondary prevention patient population includes those with established coronary and other atherosclerotic vascular disease, including peripheral arterial disease, atherosclerotic aortic disease and carotid artery disease. 8 Applying Classification of Recommendations and Level of Evidence Class I Class IIa Class IIb Class III Benefit >>> Risk Benefit >> Risk Additional studies with focused objectives needed Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Risk ≥ Benefit No additional studies needed Procedure or treatment SHOULD be performed or administered IT IS REASONABLE to perform procedure or administer treatment Procedure or treatment MAY BE CONSIDERED Procedure or treatment should NOT be performed or administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Level of Evidence A: Multiple randomized controlled trials B: Single trial, non-randomized studies C: Expert opinion 9 Secondary Prevention Definition • Therapy to reduce recurrent cardiovascular events and decrease cardiovascular mortality in patients with established atherosclerotic vascular disease • Patients covered include those with established coronary and other atherosclerotic vascular disease, including peripheral arterial disease, atherosclerotic aortic disease and carotid artery disease • Individuals with sub-clinical atherosclerosis and patients whose only manifestation is diabetes are covered in other guidelines 10 Components of Secondary Prevention Cigarette smoking cessation Blood pressure control Lipid management to goal Physical activity Weight management to goal Diabetes management to goal Antiplatelet agents / anticoagulants Renin angiotensin aldosterone system blockers Beta blockers Influenza vaccination 11 Evidence Based Therapies The writing group emphasizes the importance of giving consideration to the use of cardiovascular medications that have been proven to be of benefit in randomized clinical trials. This approach strengthens the evidence-based foundation for therapeutic application of these guidelines. The committee acknowledges that in many trials there is under-representation of ethnic minorities, women, and the elderly. 12 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. I IIa IIb III •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. 13 Blood Pressure Control Recommendations Goal: <140/90 mm Hg I IIa IIb III 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 I IIa IIb III 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 14 Blood Pressure: Lower is Better Age at Risk (Y) 80-89 256 128 70-79 64 60-69 32 50-59 16 40-49 8 4 2 1 0 Ischemic Heart Disease Mortality Ischemic Heart Disease Mortality Ischemic Heart Disease Mortality 256 Age at Risk (Y) 80-89 128 70-79 64 60-69 32 50-59 16 40-49 8 4 2 1 0 120 140 160 180 Usual Systolic BP (mm Hg) BP=Blood pressure Prospective Studies Collaboration. Lancet. 2002;360:1903-1913 70 80 90 100 110 Usual Diastolic BP (mm Hg) Long-Term Antihypertensive Therapy Significantly Reduces CV Events Stroke Myocardial infarction Heart failure 0 –10 Average reduction in events (%) –20 –30 20%-25% –40 –50 35%-40% >50% –60 Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet. 2000;355:1955-1964. 16 JNC VII Lifestyle Modifications for BP Control Modification Recommendation Approximate SBP Reduction Range Maintain normal body weight (BMI=18.5-24.9) 5-20 mmHg/10 kg weight lost Diet rich in fruits, vegetables, low fat dairy and reduced in fat 8-14 mmHg Restrict sodium intake <2.4 grams of sodium per day 2-8 mmHg Physical activity Regular aerobic exercise for at least 30 minutes on most days of the week 4-9 mmHg Moderate alcohol consumption <2 drinks/day for men and <1 drink/day for women 2-4 mmHg Weight reduction Adopt DASH eating plan BMI=Body mass index, SBP=Systolic blood pressure Chobanian AV et al. JAMA. 2003;289:2560-2572 17 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 Diuretic, BB, ACEI, ARB, CCB NKF-ADA Guideline, UKPDS, ALLHAT Diabetes Mellitus Chronic Kidney Disease Recurrent Stroke Prevention ACEI, ARB NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK 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 18 Lipid Management Goal I IIa IIb III Use statin therapy to achieve LDL-C less than 100 mg/dL I IIa IIb III For high risk patients reduction to LDL-C to < 70 mg/dL is reasonable • If it is not possible to attain LDL-C <70 mg/dL because of a high baseline LDL-C, it generally is possible to achieve LDL-C reductions of >50% with more intensive LDL-C─lowering therapy, including drug combinations. If TG >200 mg/dL, non-HDL-C should be < 130 mg/dL* *Non-HDL-C = total cholesterol minus HDL-C 19 Lipid Management Recommendations For all patients I IIa IIb III 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 I IIa IIb III I IIa IIb III 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. 20 ATP III Dietary Recommendations Nutrient Saturated fat* Recommended Intake <7% of total calories Polyunsaturated fat Up to 10% of total calories Monounsaturated fat Up to 20% of total calories Total fat 25%–35% of total calories Carbohydrate (esp. complex carbs) 50%–60% of total calories Fiber Protein Cholesterol 20–30 g/d ~15% of total calories <200 mg/d *Trans fatty acids also raise LDL-C and should be kept at a low intake. Note: Regarding total calories, balance energy intake and expenditure to maintain desirable body weight. ATP=Adult Treatment Panel Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497. 21 Impact of Omega-3 Fatty Acid Supplements in Patients Post Myocardial Infarction 11,324 patients post MI randomized to Omega-3 FA supplements 1g/d vs placebo Lancet 1999; 354: 447-55 22 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: I IIa IIb III If baseline LDL-C > 100 mg/dL, initiate LDL-lowering drug therapy I IIa IIb III If on-treatment LDL-C > 100 mg/dL, intensify LDLlowering drug therapy (may require LDL lowering drug combination) I IIa IIb III 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. 23 Simvastatin Reduced the Risk of Major Coronary Events Subgroup Analyses From The Simvastatin Survival Study 0 Percent Risk Reduction -10 -20 -30 -31 -34 -40 P<0.00001 n=1814 -35 -34 P=0.01 n=407 P<0.0005 n=1156 -50 P<0.002 n=542 -37 P<0.002 n=573 -55 -60 P=0.002 n=105 -70 Men 4S Study Wom en Lancet 1994;344:1383 Older Sm okers Hypertension Diabetes 24 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 Baseline LDL-C (mg/dL) Statin (n = 10,269) Placebo (n = 10,267) <100 282 (16.4%) 358 (21.0%) 100–129 668 (18.9%) 871 (24.7%) 130 1083 (21.6%) 1356 (26.9%) All patients 2033 (19.8%) 2585 (25.2%) Event Rate Ratio (95% CI) Statin Better Statin Worse 0.76 (0.72–0.81) P<0.0001 0.4 0.6 0.8 CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus, HPS Collaborative Group. Lancet 2002;360:7-22 1.0 1.2 1.4 25 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 Recurrent MI or Cardiac Death 30 Atorvastatin Pravastatin 25 16% RRR 20 15 10 5 P =0.005 0 3 6 9 12 15 18 21 24 27 30 Follow-up (months) ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction Cannon CP et al. NEJM 2004;350:1495-1504 26 TNT: Primary Efficacy Outcome Measure First Major Cardiovascular Event* Proportion of patients experiencing major cardiovascular event 0.15 HR = 0.78 (95% CI 0.69, 0.89) P=0.0002 Relative risk reduction = 22% Atorvastatin 10 mg 0.10 Atorvastatin 80 mg 0.05 0 0 1 2 3 Time (years) 4 5 * CHD death, nonfatal non-procedure-related MI, resuscitated cardiac arrest, fatal or nonfatal stroke LaRosa et al. N Engl J Med 2005:352 online 6 27 HMG-CoA Reductase Inhibitor: Secondary Prevention Relationship between LDL Levels and Event Rates in Secondary Prevention Trials of Patients with Stable CHD 30 4S Statin Placebo Event (%) 25 4S 20 LIPID 15 LIPID CARE 10 HPS 5 0 CARE HPS TNT (atorvastatin 10 mg/d) TNT (atorvastatin 80 mg/d) 0 70 90 110 130 150 LDL-C (mg/dL) 170 190 210 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 AIM-HIGH Primary Outcome Cumulative % with Primary Outcome 50 Statin- Niacin ER Combination Therapy Statin Monotherapy 40 30 HR 1.02, 95% CI 0.87, 1,21 Log-rank P value= 0.79 20 16.4% 16.2% 10 0 0 1 Combination Therapy 3 4 Time (years) N at risk Monotherapy 2 1696 1581 1381 910 436 1718 1606 1366 903 428 29 Physical Activity Recommendations Goal: 30 minutes 7 days/week, minimum 5 days/week I IIa IIb III Assess risk with a physical activity history and/or an exercise test, to guide prescription I IIa IIb III Encourage 30 to 60 minutes of moderate intensity aerobic activity such as brisk walking, on most, preferably all, days of the week, supplemented by an increase in daily lifestyle activities I IIa IIb III Advise medically supervised programs for high-risk patients (e.g. recent acute coronary syndrome or revascularization, HF) 30 Exercise Evidence: Mortality Risk Observational study of self-reported physical activity in 772 men with established coronary heart disease Wannamethee SG et al. Circulation 2000;102:1358-1363 31 Weight Management Recommendations Goal: BMI 18.5 to 24.9 kg/m2 Waist Circumference: Men: < 40 inches Women: < 35 inches I IIa IIb III I IIa IIb III I IIa IIb III Assess BMI and/or waist circumference on each visit and consistently encourage weight maintenance/ reduction through an appropriate balance of physical activity, caloric intake, and formal behavioral programs when indicated. If waist circumference (measured at the iliac crest) >35 inches in women and >40 inches in men initiate lifestyle changes and consider treatment strategies for metabolic syndrome as indicated. The initial goal of weight loss therapy should be to reduce body weight by approximately 10 percent from baseline. With success, further weight loss can be attempted if indicated. *BMI is calculated as the weight in kilograms divided by the body surface area in meters2. Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2. 32 CV Risk Increases with Body Mass Index Hazard Ratio Hemorrhagic Stroke Ischemic Stroke Ischemic Heart Disease 4.0 4.0 4.0 2.0 2.0 2.0 1.0 1.0 1.0 0.5 0.5 0.5 16 20 24 28 32 36 16 20 24 28 32 36 Body Mass Index (kg/m2)* CV=Cardiovascular Body mass index is calculated as the weight in kilograms divided by the body surface area in meters2. Mhurchu N et al. Int J Epidemiol 2004;33:751-758 16 20 24 28 32 36 33 Relative Risk of Cardiovascular Disease Mortality Overweight and Obesity Increase the Risk of Cardiovascular Disease Mortality and All-Cause Mortality CVD mortality 3.0 Men Women 2.6 2.2 1.8 1.4 1.0 0.6 Normal weight Overweight >18 25 Obese 30 >40 Relative Risk of All- Cause Mortality BMI (kg/m2) All-cause mortality Men Women 3.0 2.6 2.2 1.8 1.4 1.0 0.6 Normal weight Overweight >18 25 Obese 30 >40 BMI (kg/m2) Data are from 1 million men and women followed for 16 years with an average age of 57 who never smoked and had no history of disease at enrollment. Calle et al. N Engl J Med. 1999;341:1097-1105. 34 Metabolic Syndrome: Risk of Developing DM Diabetes Prevention Program (DPP) Incidence of DM (%) 3,234 patients with elevated fasting and post-load glucose levels randomized to placebo, metformin (850 mg twice daily), or lifestyle modification* for 2.8 years Placebo Metformin Lifestyle modification 40 20 0 1 2 3 4 Lifestyle modification reduces the risk of developing DM *Includes 7% weight loss and at least 150 minutes of physical activity per week Knowler WC et al. NEJM 2002;346:393-403 35 Diabetes Mellitus Recommendations I IIa IIb III I IIa IIb III I IIa IIb III Lifestyle modifications including daily physical activity, weight management, blood pressure control, and lipid management are recommended for all patients with diabetes. Coordinate diabetic care with patient’s primary care physician or endocrinologist. A target HbA1c of ≤7% may be considered HbA1c = Glycosylated hemoglobin 36 Primary Composite Endpoint* (%) Intensive Multiple Risk Factor Management Patients with Type 2 Diabetes: STENO-2 60 N=160; follow-up=7.8 years Conventional Therapy 40 20% Absolute Risk Reduction 20 Aggressive treatment of†: – Microalbuminuria with ACEIs, ARBs, or combination – Hypertension – Hyperglycemia – Dyslipidemia – Secondary prevention of CVD Intensive Therapy† 12 24 36 48 60 72 84 96 Months of Follow-Up Primary composite endpoint: conventional therapy (44%) and intensive therapy (24%). *Death from CV causes, nonfatal MI, CABG, PCI, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic artery disease. †Behavior modification and pharmacologic therapy. Adapted from Gaede P, et al. N Eng J Med. 2003;348:383-393. 37 Antiplatelet Agents / Anticoagulation Recommendations 38 Aspirin Recommendations I IIa IIb III Start and continue indefinitely aspirin 75 to 162 mg/d in all patients unless contraindicated I IIa IIb III For patients undergoing CABG, aspirin (100 to 325 mg/d) should be started within 48 hours after surgery to reduce saphenous vein graft closure I IIa IIb III 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 Aspirin Evidence: Secondary Prevention Effect of antiplatelet therapy* on vascular events** 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 0.0 0.5 1.0 1.5 2.0 Antiplatelet better Control better *Aspirin was the predominant antiplatelet agent studied **Vascular events include MI, stroke, or death Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86. 39 40 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<.0001 0.5 Antiplatelet Better Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86 1.0 1.5 2.0 Antiplatelet Worse 41 Clopidogrel Recommendations Start and continue clopidogrel 75 mg/d in combination with aspirin I IIa IIb III for post ACS or post PCI with stent placement patients for up to 12 months for post PCI-stented patients >1 month for bare metal stent, >12 months for sirolimus-eluting stent >12 months for paclitaxel-eluting stent *Clopidogrel is generally given preference over Ticlopidine because of a superior safety profile 42 Clopidogrel Evidence: ACS (Non-STEMI and UA) Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial Rate of death, myocardial infarction, or stroke 12,562 patients with a NSTEMI-ACS randomized to daily aspirin (75-325 mg) or clopidogrel (300 mg load, 75 mg thereafter) plus aspirin (75-325 mg) for 3-12 months (average 9 months) 0.14 Aspirin + Clopidogrel Aspirin + Placebo 0.12 0.10 0.08 0.06 0.04 0.02 P<0.001 0.00 0 3 6 Months of Follow Up NSTEMI-ACS=Non ST-segment elevation acute coronary syndrome The CURE Trial Investigators. NEJM. 2001;345:494-502 9 12 43 CHARISMA: Primary Efficacy Outcome (MI, Stroke, or CV Death)† Cumulative event rate (%) 8 Placebo + ASA* 7.3% 6 Clopidogrel + ASA* 6.8% 4 RRR: 7.1% [95% CI: -4.5%, 17.5%] P = 0.22 2 0 0 6 12 18 24 Months since randomization§ † 30 First Occurrence of MI (fatal or non-fatal), stroke (fatal or non-fatal), or cardiovascular death *All patients received ASA 75-162 mg/day §The number of patients followed beyond 30 months decreases rapidly to zero and there are only 21 primary efficacy events that occurred beyond this time (13 clopidogrel and 8 placebo) Adapted with permission from Bhatt DL, et al. N Engl J Med. 2006;354. 44 Anticoagulation Recommendations I IIa IIb III I IIa IIb III Manage warfarin to international normalized ratio 2.0 to 3.0 for paroxysmal or chronic atrial fibrillation or flutter, and in post-MI patients when clinically indicated (e.g., atrial fibrillation, LV thrombus.) Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with increased risk of bleeding and should be monitored closely 45 Renin-Angiotensin-Aldosterone System Blockers Recommendations 46 ACE Inhibitor Recommendations I IIa IIb III Use in all patients with LVEF < 40%, and those with diabetes or chronic kidney disease indefinitely, unless contraindicated I IIa IIb III Consider for all other patients I IIa IIb III Among lower risk patients with normal LVEF where cardiovascular risk factors are well controlled and where revascularization has been performed, their use may be considered optional ACE=Angiotensin converting enzyme, LVEF= left ventricular ejection fraction 47 ACE Inhibitor Evidence: Post MI with LVD or HF AIRE SAVE Probability of Event Radionuclide EF 40% 0.4 TRACE Clinical and/or radiographic signs of HF Echocardiogram EF 35% Placebo 0.35 ACE-I 0.3 0.25 0.2 0.15 0.1 OR: 0.74 (0.66–0.83) 0.05 0 0 1 2 3 4 Years ACE-I=Angiotensin converting enzyme inhibitors, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio Flather MD, et al. Lancet. 2000;355:1575–1581 48 ACE Inhibitor Evidence: CAD, CVD, PVD or DM Heart Outcomes Prevention and Evaluation (HOPE) Study CV death, MI, or stroke (%) 9,297 patients with DM or vascular disease plus one additional CV risk factor, but without HF or known LVSD randomized to ramipril (10 mg) or placebo for 5 years 0.20 Ramipril 0.15 Placebo 0.10 0.05 22% RRR, P<0.001 0.00 0 500 1000 1500 Days of Follow-Up ACE-I=Angiotensin converting enzyme inhibitors, DM=Diabetes mellitus, CV=Cardiovascular, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction HOPE Investigators. NEJM 2000;342:145-153 49 ACEI Therapy in Patients with Atherosclerosis Relative Risk of Mortality Clinical Trial N Deaths HOPE 9,297 1051 HR 0.84 P=0.005 EUROPA 12,218 795 HR 0.89 P=0.10 PEACE 8,290 All Trials 33,960 633 HR 0.89 P=0.13 HR 0.86 P<0.001 >3000 0.4 0.6 0.8 1.0 ACEI Better 1.2 1.4 1.6 Placebo Better 7 RCT, 33,960 randomized, 4.4 year follow-up, CVD HR 0.81, MI HR 0.82, Stroke HR 0.77 Danchin et al Arch Intern Med 2006;166:787-796 50 Angiotensin Receptor Blocker Recommendations I IIa IIb III Use in patients who are intolerant of ACE inhibitors with HF or post MI with LVEF less than or equal to 40%. I IIa IIb III Consider in other patients who are ACE inhibitor intolerant. I IIa IIb III Consider use in combination with ACE inhibitors in systolic dysfunction HF. ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction, HF=Heart failure, MI=Myocardial infarction 51 ARB Evidence: Post MI with LVD or HF Valsartan in Acute Myocardial Infarction Trial (VALIANT) All Cause Mortality 14,703 patients with post-MI HF or LVSD (EF <0.40) randomized to captopril (50 mg three times daily), valsartan (160 mg twice daily), or captopril (50 mg three times daily) plus valsartan (80 mg twice daily) over 2 years 0.4 Captopril 0.3 Valsartan Valsartan and Captopril 0.2 0.1 Valsartan vs. Captopril: HR = 1.00; P = 0.982 Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726 0.0 0 6 12 18 24 30 36 Months EF=Ejection fraction, HR=Hazard ratio, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, RAS=Renin angiotensin system Pfeffer M et al. NEJM 2003;349:1893-1906. 52 ARB Evidence: Stable CAD or Diabetes Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs 0.20 0.15 Cumulative hazard ratio N = 25,620 with vascular disease or high-risk diabetes 0.10 0.05 0.00 0 1 2 3 4 5 Follow-up (years) Telmisartan Ramipril OnTarget Investigators NEJM 2008;358:1547-1559. Telmisartan plus ramipril 53 Aldosterone Antagonist Recommendations I IIa IIb III Use in post MI patients, without significant renal dysfunction or hyperkalemia, who are already receiving therapeutic doses of an ACE inhibitor and beta blocker, have an LVEF < 40% and either diabetes or heart failure *Contraindications include abnormal renal function (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) and hyperkalemia (K+ >5.0 meq/L) ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction, MI=Myocardial infarction 54 Aldosterone Antagonist: Heart Failure Randomized Aldactone Evaluation Study (RALES) 1,663 patients with NYHA Class III or IV HF and LVSD (EF <0.35) randomized to spironolactone (25 mg) or placebo (50 mg) for 24 months Survival (%) 1.00 Spironolactone Placebo .90 .80 .70 .60 .50 RR = 0.70, P<0.001 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NYHA=New York Heart Association Pitt B et al. NEJM 1999;341:709-717 55 Aldosterone Antagonist: Post MI HF and LVSD Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) All Cause Mortality (%) 6,644 patients with evidence of heart failure and LVSD (EF <0.40) after a MI randomized to eplerenone (50 mg) or placebo for 16 months Eplerenone Placebo 25 20 15 10 5 0 RR = 0.85, P=0.008 0 6 12 18 24 30 Month EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction Pitt B et al. NEJM 2003;348:1309-21 36 Eplerenone in Patients with Systolic HF and Mild Symptoms: EMPHASIS HF Primary Endpoint: CV Mortality and HF Hospitalization 50 Primary Endpoint: Cumulative K-M Rate (%) HR = 0.63 (0.54-0.74), p <0.001 40 Placebo 356 (25.9%) Eplerenone 249 (18.3%) 30 20 10 0 0 No. at Risk Placebo Eplerenone 1373 1364 1 2 Years from Randomization 848 925 Zannad F. New Engl J Med. 2011;364:11-21. 512 562 3 199 232 57 b-blocker Recommendations 58 b-blocker Recommendations I IIa IIb III Beta-blocker therapy should be used in all patients with left ventricular systolic dysfunction (ejection fraction 40%) with heart failure or prior myocardial infarction, 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 therapy should be started and continued for 3 years in all patients with normal left ventricular function who have had myocardial infarction or ACS I IIa IIb III Consider chronic therapy for all other patients with coronary or other vascular disease or diabetes unless contraindicated. MI=Myocardial infarction, HF=Heart Failure 59 b-blocker Evidence Summary of Secondary Prevention Trials of b-blocker Therapy Phase of Treatment Total # Patients RR (95% CI) Acute treatment 28,970 0.87 (0.77-0.98) Secondary prevention 24,298 0.77 (0.70-0.84) Overall 53,268 0.81 (0.75-0.87) 0.5 CI=Confidence interval, RR=Relative risk 1.0 RR of death b-blocker Placebo better better 2.0 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. b-blocker Evidence: Post MI with 60 Left Ventricular Dysfunction Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN) Proportion Event-free 6,644 patients with LVEF <0.40 after a MI with or without HF randomized to carvedilol or placebo for 24 months 1 0.95 n=975 0.9 Carvedilol n=984 0.85 0.8 0.75 0.7 RR 0.77 P=.03 0 0.5 1 1.5 Years The CAPRICORN Investigators. Lancet. 2001;357:1385–1390. Placebo 2 2.5 61 b-blocker Evidence: Benefit in HF and LVSD US Carvedilol Study*1 CIBIS II2 1.0 Carvedilol (n=696) 0.8 Placebo (n=398) Survival Survival 1.0 Risk Reduction=65% P<.001 0.6 Bisoprolol (n=1327) 0.8 Risk Reduction=34% P<.0001 0.6 0 0 0 3 6 9 0 12 3 MERIT-HF3 1.0 6 9 12 15 18 21 24 Time After Inclusion (months) Months 1.0 COPERNICUS4 Metoprolol CR/XL (n=1990) 0.8 Placebo (n=2001) 0 0 1Packer 3 6 9 12 15 18 Months of Follow-up 0.8 P=.0014 0 21 Placebo (n=1133) Risk Reduction=35% 0.6 Risk Reduction=34% P=.0062 0.6 Carvedilol (n=1156) Survival Survival Placebo (n=1320) 0 3 6 9 12 15 18 21 Months M et al. N Engl J Med. 1996;334:1349-1355. 2CIBIS II Investigators and Committees. Lancet. 1999;353:9-13. 3MERIT-HF Study Group. Lancet. 1999;353:2001-2007. 62 Influenza Vaccination I IIa IIb III Patients with cardiovascular disease should have influenza vaccination 63 Influenza Vaccination Evidence Effectiveness of Influenza Vaccination during the Influenza Seasons Hospitalization Vaccinated Unvaccinated Subjects Subjects (N=77,738) (N=62,317) 495 (0.6) 581 (0.9) Adjusted Odds Ratio P value 0.68 Pneumonia or influenza <0.001 (0.60–0.78) 0.81 Cardiac disease 888 (1.1) 1026 (1.6) <0.001 (0.73–0.89) 0.80 Ischemic heart disease 457 (0.6) 535 (0.9) 0.001 (0.70–0.91) 0.81 Heart failure 466 (0.6) 538 (0.9) 0.002 (0.70–0.92) 0.84 Cerebrovascular disease 398 (0.5) 427 (0.7) 0.018 (0.72–0.97) 0.52 Death 943 (1.2) 1361 (2.2) <0.001 (0.47–0.57) 0.65 Hospitalization or death 2387 (3.1) 2910 (4.7) <0.001 (0.62–0.70) Community cohort of 140,055 subjects in the 1998–1999 season of which 55.5 % were immunized. Nichol et al. N Engl J Med 2003;348:1322-32. 64 Therapies Not Recommendations 65 Impact of Vitamin E Supplementation in Men and Women Post Myocardial Infarction GISSI Prevention 100 % Surviving (free of MI, stroke, death) n=5660 95 n=5664 90 Vitamin E Placebo 85 RR 0.95 (0.86-1.05) P=0.293 80 75 70 0 6 12 18 24 30 36 42 Months 11,324 patients post MI randomized to Vitamin E 300 mg/d vs placebo 1700 women, ave age 59 92% asa, 44% bb, 50% acei, 20% statin Lancet 1999; 354: 447-55 48 66 Hormone Replacement as a Therapeutic Agent in Cardiovascular Disease RH 1.24 (0.87-1.75) 2763 Postm enopausal w om en w ith CAD: 0.625 Equine Estrogen and 2.5 m g MPA vs Placebo 14% reduction in LDL and 8% increase in HDL HERS Research Group Hulley JAMA:280:605-613 67 Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease HOPE 2 N Engl J Med 2006;354:1567-1577 Bonna N Engl J Med 2006;354:1578-1588 68 Atherosclerosis as the Therapeutic Target Therapies with Demonstrated Benefit Anti-Platelet Therapy Aspirin and/or Clopidigrel Neurohumoral Inhibition Beta Blockers ACE Inhibitors Lipoproteins / Inflammation Statins (irrespective of baseline LDL) Omega-3 Fatty Acids Exercise Smoking Cessation 69 Conceptual Basis for Combination Cardiovascular Protective Medical Therapy for Atherosclerosis Hypertension Apo B100 Lp (a) Triglycerides CRP Activated monocytes Angiotensin II Aldosterone Serum amyloid IL-6 Obesity M-CSF ECAM ICAM Oxidized LDL Fibrinogen P-selectin AGEs Chylomicron Remnants Diabetes Epinephrine Endothelin Tissue Factor NAPDH oxidases Norepinephrine Superoxide anion Iron TNF CD-40 ligand Particulate matter Insulin Xanthine oxidase PAI-1 Myeloperoxidase Uric acid Smoking Aponectin Homocysteine Chlamydia Apo E PDGF Age Small dense LDL ADMA 70 Interaction Between Therapies to Treat Atherosclerosis 28.9 Placebo Only 18.6 Statin Only 11.2 Statin+ASA 8.6 70% Reduction Statin+ASA+BB 0 5 10 15 20 25 30 35 Coronary Event Rate (%) Treatment in 4S 4444 Patients with CAD Only statin vs placebo randomized 5.4 years F/U Placebo 24% Statin 24% Statin+ASA 8% Statin+ASA+Beta Blocker 18% 71 Statin Therapy is Additive to Other Cardioprotective Therapies in Patients with Atherosclerosis or Diabetes Background Therapy Relative Risk of CV Event N Aspirin + Aspirin - 12984 7552 Beta Blocker + Beta Blocker - 5279 15257 ACE Inhibitor + ACE Inhibitor - 3979 16557 0.4 0.6 0.8 1.0 Simvastatin Better 1.2 1.4 1.6 Placebo Better P=NS Heart Protection Study Lancet 2002;360:7-22. Test for heterogeneity 72 ACEI Therapy is Additive to Other Cardioprotective Therapies in Patients with Atherosclerosis or Diabetes Background Therapy Relative Risk of CV Event N Aspirin + Aspirin - 6813 2484 Beta Blocker + Beta Blocker - 3673 5624 Lipid Lowering + Lipid Lowering - 2658 6639 0.4 0.6 0.8 1.0 Ramipril Better 1.2 1.4 1.6 Placebo Better P=NS Dagenais Circulation 2001;104:522-526. Test for heterogeneity 73 Cumulative Impact of Simple Cardiovascular Protective Medications Relative-risk 2 yr CV event rate None -- 20% Aspirin 25% 15% Beta blocker 25% 11.3% ACE inhibitor 25% 8.4% Lipid lowering Rx 30% 5.9% LDL 100 16% 5.0% 70 mg/dl Cumulative risk reduction if all four therapies are used: 75% Absolute risk reduction: 15%, NNT = 6 CV event = CV death, MI, or stroke Fonarow Am J Cardiol 2001;85:10A-17A and Yusuf Lancet 2002;360:2-3 74 The Need to Implement Secondary Prevention Multiple studies of the use of these recommended therapies in appropriate patients continue to show that many patients in whom therapies are indicated are not receiving them in actual clinical practice. The AHA and ACC urge that in all medical care settings where these patients are managed that programs to provide practitioners with useful reminder clues based on the guidelines, and continuously assess the success achieved in providing these therapies to the patients who can benefit from them be implemented. Encourage that the AHA’s Get With the Guidelines and/or ACC’s Guidelines Applied to Practice Programs be instituted to identify appropriate patients for therapy Making Sure All Patients Get Indicated Therapy: The UCLA CHAMP Program 75 Patient with coronary, cerebral, or peripheral atherosclerosis (documented by clinical, ultrasound, stress test or angiographic criteria) Obtain admission lipid panel, liver function tests Hospital Phase of Care Start : • Aspirin, clopidogrel or both • Beta blocker • ACE inhibitor • Statin • Exercise, omega 3FA, and dietary counseling Obtain lipid panel, liver function tests Outpatient Phase of Care LDL > 70 mg/dL LDL < 70 mg/dL Advance statin dose and/or combination rx Continue treatment Reinforce compliance Recheck in 3-6 months Continue treatment Recheck in 6 weeks 76 Implementation of CHAMP Focused Treatment Guidelines and Algorithm Preprinted Admit Order Sheets Discharge Forms and Outpt F/U Process Patient Education Materials CHAMP tool kit: www.med.ucla.edu/champ Fonarow GC et al. Am J Cardiol 2000;85:10A-17A. Focused Lectures by Opinion Leaders Measurement and Utilization Reports 77 Proof of Concept: CHAMP CAD Patient Treatment Rates Pre-CHAMP Hospital discharge: Aspirin Beta-Blocker ACEI Statin 12-month follow-up: Statin LDL < 100 mg/dL Fonarow Am J Cardiol 2001;87:819-822 Post-CHAMP ‘92-’93 ‘94-’95 (n=256) (n=302) 78% 12% 4% 6% 92%* 61%* 56%* 86%* 10% 6% 91%* 58%* 78 CHAMP: Sustained Impact Over a 10-Year Period Comparison of UCLA (1992–2003) to NRMI IV (2002/2003) National Rx Rates 92/93 100 90 80 70 60 50 40 30 20 10 0 92 91 94 92 94/95 96 96/97 92 68 68 72 78 00/01 82 64 02/03 88 89 90 91 88 90 85 85 98/99 92 70 52 58 52 12 6 4 ASA Beta-Blocker ACEI Statin National Registry of Myocardial Infarction Discharge Medications at UCLA compared with 1283 NRMI hospitals. Revised from Fonarow GC et al. Circulation. 2001;104:II-711. 79 CHAMP Study: Clinical Events for the First Year After Discharge for Acute MI 15 14.8 * P < .05 Pre-CHAMP Post-CHAMP 10 7.6* 7.8 5 7.0 4.7 3.3* 3.1* 2.6 0 Recurrent MI Heart Failure Fonarow GC, et al. Am J Cardiol. 2001;87:819-822. Hospitalization Total Mortality 80 Why a Hospital-based System for ACS and Heart Failure Management? • Patients – Patient capture point – Have patient’s/family’s attention: “teachable moment” – Predictor of care in community • Hospital structure – Standardized processes/protocols/ orders/teams – Accrediting bodies for standards of care – Centers for Medicare and Medicaid Services (CMS) and peer review organizations • JCAHO (in-hospital) • HEDIS (post-discharge) 81 AHA GWTG Program GWTG is a national initiative of the AHA to improve guidelines adherence in patients hospitalized with cardiovascular disease. GWTG uses collaborative learning sessions, conference calls, e-mail and staff support to assist hospital teams improve acute and secondary prevention care systems. A web-based Patient Management Tool is used for point of care data collection and decision support, on-demand reporting, communication and patient education. 82 SIMPLE, ONE PAGE, ON-LINE FORM Demographics 6 clicks Clinical/Lab 8 clicks Discharge meds and interventions 7 clicks Interactively checks patient’s data with the AHA guidelines ©2001 Outcome Sciences, Inc. 83 Impact of AHA Get With The Guidelines-CAD Program on Quality of Care Baseline * 100 90 80 70 60 50 40 30 20 10 0 * * 97 9796 95 93 Q1 Q2 8787 * 64656567 Aspirin Q4 * p< 0.05 compared to baseline * * * 91 83 79 Q3 68 Beta Blocker ACE Inhibitor GWTG-CAD: 123 US Hospitals n=27,825 Labresh, Fonarow et al. Circulation 2003;108:IV-722 * * * 75 73 6770 74 * * * 82 * 7675 70 57 Lipid Rx Smoking Cessation 84 GWTG Associated with Improved Treatment at Teaching and Non-Teaching Hospitals Baseline 100 90 80 70 60 50 40 30 20 10 0 Q1 * 85 * 56 68 * 62 Q3 Q4 * * * 85 * 81 76 67 67 * * 88 88 * 75 77 * * Q2 * 86 * 79 75 72 58 62 43 Teaching Non-Teaching Smoking Cessation GWTG-CAD: 123 US Hospitals n=27,825 Fonarow et al. Circulation 2003;108:IV-721 Teaching Non-Teaching Cardiac Rehab/Exercise * p< 0.05 compared to baseline 85 Results with GWTG-HF: Performance Measures Baseline P=0.127 100 90 80 70 60 50 40 30 20 10 0 p<0.0001 70 74 74 75 Q1 Q2 83 81 83 82 DC Instructions Q4 P=0.046 P=0.036 91 92 92 92 91 79 Q3 85 87 87 86 84 p<0.0001 90 89 81 82 81 74 LVF Measurement ACEI/ARB Beta Blocker Data from 97 GWTG-HF hospitals and 18,516 HF patients were collected from 1/05-3/06 Fonarow GC et al. Submitted HFSA 2006 Smoking Cessation 86 The Science of Implementation It is possible to create a hospital based system to implement atherosclerosis treatment In-hospital treatment rates are markedly improved It is safe to initiate lipid-lowering and other cardioprotective medications in the hospital In-hospital initiated treatments are continued by outpatient physicians In-hospital initiation of treatments markedly improves long term patient compliance In-hospital initiation of lipid lowering therapy results in more patients reaching a LDL < 100 mg/dl It reduces total medical costs In-hospital initiation of cardioprotective therapies reduces recurrent CV events and saves lives 87 Key Elements to Quality Improvement: Why Do Some Programs Succeed? • Access to current and accurate data on treatment and outcomes • Have stated goals • Administrative support • Support among clinicians • Use of care maps and pathways • Use of data to provide feedback Bradley EH, et al. JAMA. 2001;285:2604-2611. 89 Secondary Prevention: Medications Goals • Aspirin • BP <140/90 mm Hg (<130/80 mm Hg with diabetes or CKD) • Clopidogrel • β-blockers • ACE inhibitors/ARBs • Aldosterone blockade (Low EF) • Lipids - Fasting lipid panel within 24 h of hospitalization – Statins before discharge – Goal LDL-C <100 mg/dL – LDL <70 mg/dL is reasonable Anderson JL, et al. J Am Coll Cardiol. 2007;50:652-726. King SB 3rd, et al. J Am Coll Cardiol. 2008;51:172-209. • Smoking cessation/no environmental smoke exposure • Physical activity (30 min, 7 d/wk; min 5 d/wk) • Weight management • Diabetes management: HbA1c <7% • Annual influenza immunization 90 Conclusions • Comprehensive application of secondary prevention therapies is highly effective in reducing the risk of cardiovascular events • Despite the clinical trial evidence and national guidelines, large number of eligible patients are not receiving one or more of these recommended therapies • As such, large number of patients are having CV events that could be avoided if there was better implementation • Every effort should be made to bridge the cardiovascular risk reduction gap