AHA/ACCF Guideline AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update A Guideline From the American Heart Association and American College of Cardiology Foundation Endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association 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 Since the 2006 update of the American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) guidelines on secondary prevention,1 important evi- dence from clinical trials has emerged that further supports and broadens the merits of intensive risk-reduction therapies for patients with established coronary and other atherosclerotic vascular disease, including peripheral artery disease, atheroscle- rotic aortic disease, and carotid artery disease. In reviewing this evidence and its clinical impact, the writing group believed it would be more appropriate to expand the title of this guideline to Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease. Indeed, the growing body of evidence confirms that in patients with atherosclerotic vascular disease, comprehensive risk factor management reduces risk as assessed by a variety of outcomes, including improved survival, reduced recurrent events, the need for revascularization procedures, and improved quality of life. It is important not only that the healthcare provider implement these recommendations in appropriate patients but also that healthcare systems support this implementation to maximize the benefit to the patient. Compelling evidence-based results from recent clinical trials and revised practice guidelines provide the impetus for this update of the 2006 recommendations with evidence-based re- sults2 165 (Table 1). Classification of recommendations and level of evidence are expressed in ACCF/AHA format, as detailed in Table 2. Recommendations made herein are largely based on major practice guidelines from the National Institutes of Health and updated ACCF/AHA practice guidelines, as well as on results from recent clinical trials. Thus, the development of the present guideline involved a process of partial adaptation of other guideline statements and reports and supplemental litera- The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This document was approved by the American Heart Association Science Advisory and Coordinating Committee on October 5, 2011, and by the American College of Cardiology Foundation Board of Trustees on September 29, 2011. The American Heart Association requests that this document be cited as follows: Smith SC Jr, Benjamin EJ, Bonow RO, Braun LT, Creager MA, Franklin BA, Gibbons RJ, Grundy SM, Hiratzka LF, Jones DW, Lloyd-Jones DM, Minissian M, Mosca L, Peterson ED, Sacco RL, Spertus J, Stein JH, Taubert KA. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124:2458 2473. Copies: This document is available on the World Wide Web site of the American Heart Association (my.americanheart.org). A copy of the document is available at http://my.americanheart.org/statements by selecting either the By Topic link or the By Publication Date link. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com. Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development, visit http://my.americanheart.org/statements and select the Policies and Development link. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/ Copyright-Permission-Guidelines_UCM_300404_Article.jsp. A link to the Copyright Permissions Request Form appears on the right side of the page. 2011 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0b013e318235eb4d Table 1. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update: Intervention Recommendations With Class of Recommendation and Level of Evidence Area for Intervention Recommendations Smoking Goal: Complete cessation. No exposure to environmental tobacco smoke Class I 1. Patients should be asked about tobacco use status at every office visit.2,3,4,5,7 (Level of Evidence: B) 2. Every tobacco user should be advised at every visit to quit.4,5,7,9 (Level of Evidence: A) 3. The tobacco user s willingness to quit should be assessed at every visit. (Level of Evidence: C) 4. Patients should be assisted by counseling and by development of a plan for quitting that may include pharmacotherapy and/or referral to a smoking cessation program.4 9 (Level of Evidence: A) 5. Arrangement for follow up is recommended. (Level of Evidence: C) 6. All patients should be advised at every office visit to avoid exposure to environmental tobacco smoke at work, home, and public places.10,11 (Level of Evidence: B) Blood pressure control Goal: ,140/90 mm Hg Note: The writing committee did not think that the 2006 recommendations for blood pressure control (below) should be modified at this time. The writing committee anticipates that the recommendations will be reviewed when the updated JNC guidelines are released. Class I 1. All patients should be counseled regarding the need for lifestyle modification: weight control; increased physical activity; alcohol moderation; sodium reduction; and emphasis on increased consumption of fresh fruits, vegetables, and low-fat dairy products.12 16 (Level of Evidence: B) 2. Patients with blood pressure $140/90 mm Hg should be treated, as tolerated, with blood pressure medication, treating initially with b-blockers and/or ACE inhibitors, with addition of other drugs as needed to achieve goal blood pressure.12,17,18 (Level of Evidence: A) Lipid management Goal: Treatment with statin therapy; use statin therapy to achieve an LDL-C of ,100 mg/dL; for very high risk* patients an LDL-C ,70 mg/dL is reasonable; if triglycerides are $200 mg/dL, non HDL-C should be ,130 mg/dL, whereas non HDL-C ,100 mg/dL for very high risk patients is reasonable Note: The writing committee anticipates that the recommendations will be reviewed when the updated ATP guidelines are released. Class I 1. A lipid profile in all patients should be established, and for hospitalized patients, lipid-lowering therapy as recommended below should be initiated before discharge.20 (Level of Evidence: B) 2. Lifestyle modifications including daily physical activity and weight management are strongly recommended for all patients.19,29 (Level of Evidence: B) 3. Dietary therapy for all patients should include reduced intake of saturated fats (to ,7% of total calories), trans fatty acids (to ,1% of total calories), and cholesterol (to ,200 mg/d).21 24,29 (Level of Evidence: B) 4. In addition to therapeutic lifestyle changes, statin therapy should be prescribed in the absence of contraindications or documented adverse effects.25 29 (Level of Evidence: A) 5. An adequate dose of statin should be used that reduces LDL-C to ,100 mg/dL AND achieves at least a 30% lowering of LDL-C.25 29 (Level of Evidence: C) 6. Patients who have triglycerides $200 mg/dL should be treated with statins to lower non HDL-C to ,130 mg/dL.25 27,30 (Level of Evidence: B) 7. Patients who have triglycerides .500 mg/dL should be started on fibrate therapy in addition to statin therapy to prevent acute pancreatitis. (Level of Evidence: C) Class IIa 1. If treatment with a statin (including trials of higher-dose statins and higher-potency statins) does not achieve the goal selected for a patient, intensification of LDL-C lowering drug therapy with a bile acid sequestrant or niacin is reasonable.31 33 (Level of Evidence: B) 2. For patients who do not tolerate statins, LDL-C lowering therapy with bile acid sequestrants and/or niacin is reasonable.35,36 (Level of Evidence: B) 3. It is reasonable to treat very high-risk patients* with statin therapy to lower LDL-C to ,70 mg/dL.26 28,37,38,166 (Level of Evidence: C) 4. In patients who are at very high risk* and who have triglycerides $200 mg/dL, a non HDL-C goal of ,100 mg/dL is reasonable.25 27,30 (Level of Evidence: B) (Continued) Smith et al AHA/ACCF Secondary Prevention: 2011 Update 2459 Table 1. Continued Area for Intervention Recommendations Lipid management cont d Class IIb 1. The use of ezetimibe may be considered for patients who do not tolerate or achieve target LDL-C with statins, bile acid sequestrants, and/or niacin. (Level of Evidence: C) 2. For patients who continue to have an elevated non HDL-C while on adequate statin therapy, niacin or fibratei therapy32,35,41 (Level of Evidence: B) or fish oil (Level of Evidence: C) may be reasonable. 3. For all patients, it may be reasonable to recommend omega-3 fatty acids from fish or fish oil capsules (1 g/d) for cardiovascular disease risk reduction.44 46 (Level of Evidence: B) Physical activity Class I Goal: At least 30 minutes, 7 days per week (minimum 5 days per week) 1. For all patients, the clinician should encourage 30 to 60 minutes of moderate-intensity aerobic activity, such as brisk walking, at least 5 days and preferably 7 days per week, supplemented by an increase in daily lifestyle activities (eg, walking breaks at work, gardening, household work) to improve cardiorespiratory fitness and move patients out of the least fit, least active high-risk cohort (bottom 20%).54,55,58 (Level of Evidence: B) 2. For all patients, risk assessment with a physical activity history and/or an exercise test is recommended to guide prognosis and prescription.47 52,58 (Level of Evidence: B) 3. The clinician should counsel patients to report and be evaluated for symptoms related to exercise. (Level of Evidence: C) Class IIa 1. It is reasonable for the clinician to recommend complementary resistance training at least 2 days per week.59 (Level of Evidence: C) Weight management Class I Goals: Body mass index: 18.5 to Waist circumference: women ,35 inches (,89 cm), men 1. Body mass index and/or waist circumference should be assessed at every visit, and the clinician should consistently encourage weight maintenance/reduction through an appropriate balance of lifestyle physical activity, structured exercise, caloric intake, and formal behavioral programs when indicated to maintain/achieve a body mass index .60 62,65 70 (Level of Evidence: B) 2. If waist circumference (measured horizontally at the iliac crest) is $35 inches ($89 cm) in women and $40 inches ($102 cm) in men, therapeutic lifestyle interventions should be intensified and focused on weight management.66 70 (Level of Evidence: B) 3. The initial goal of weight loss therapy should be to reduce body weight by approximately 5% to 10% from baseline. With success, further weight loss can be attempted if indicated. (Level of Evidence: C) Type 2 diabetes mellitus management Note: Recommendations below are for prevention of cardiovascular complications. Class I 1. Care for diabetes should be coordinated with the patient s primary care physician and/or endocrinologist. (Level of Evidence: C) 2. Lifestyle modifications including daily physical activity, weight management, blood pressure control, and lipid management are recommended for all patients with diabetes.19,22-24,29,56,58,59,62,66,74,162 (Level of Evidence: B) Class IIa 1. Metformin is an effective first-line pharmacotherapy and can be useful if not contraindicated.74 76 (Level of Evidence: A) 2. It is reasonable to individualize the intensity of blood sugar lowering interventions based on the individual patient s risk of hypoglycemia during treatment. (Level of Evidence: C) Class IIb 1. Initiation of pharmacotherapy interventions to achieve target HbA1c may be reasonable.71,72,74-80 (Level of Evidence: A) 2. A target HbA1c of #7% may be considered. (Level of Evidence: C) 3. Less stringent HbA1c goals may be considered for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, or extensive comorbidities, or those in whom the goal is difficult to attain despite intensive therapeutic interventions. (Level of Evidence: C) Antiplatelet agents/anticoagulants Class I 1. Aspirin 75 162 mg daily is recommended in all patients with coronary artery disease unless contraindicated.64,81,82,116 (Level of Evidence: A) Clopidogrel 75 mg daily is recommended as an alternative for patients who are intolerant of or allergic to aspirin.117 (Level of Evidence: B) 2. A P2Y12 receptor antagonist in combination with aspirin is indicated in patients after ACS or PCI with stent placement.83 85 (Level of Evidence: A) For patients receiving a bare-metal stent or drug-eluting stent during PCI for ACS, clopidogrel 75 mg daily, prasugrel 10 mg daily, or ticagrelor 90 mg twice daily should be given for at least 12 months.84,86,113,114 (Level of Evidence: A) (Continued) Table 1. Continued Area for Intervention Recommendations Antiplatelet agents/anticoagulants cont d 3. For patients undergoing coronary artery bypass grafting, aspirin should be started within 6 hours after surgery to reduce saphenous vein graft closure. Dosing regimens ranging from 100 to 325 mg daily for 1 year appear to be efficacious.87 90 (Level of Evidence: A) 4. In patients with extracranial carotid or vertebral atherosclerosis who have had ischemic stroke or TIA, treatment with aspirin alone (75 325 mg daily), clopidogrel alone (75 mg daily), or the combination of aspirin plus extended-release dipyridamole (25 mg and 200 mg twice daily, respectively) should be started and continued.91,104,116 (Level of Evidence: B) 5. For patients with symptomatic atherosclerotic peripheral artery disease of the lower extremity, antiplatelet therapy with aspirin (75 325 mg daily) or clopidogrel (75 mg daily) should be started and continued.92,107,116,117 (Level of Evidence: A) 6. Antiplatelet therapy is recommended in preference to anticoagulant therapy with warfarin or other vitamin K antagonists to treat patients with atherosclerosis.93,94,105,110 (Level of Evidence: A) If there is a compelling indication for anticoagulant therapy, such as atrial fibrillation, prosthetic heart valve, left ventricular thrombus, or concomitant venous thromboembolic disease, warfarin should be administered in addition to the low-dose aspirin (75 81 mg daily).95,99 102 (Level of Evidence: A) For patients requiring warfarin, therapy should be administered to achieve the recommended INR for the specific condition.81,96 (Level of Evidence: B) Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with increased risk of bleeding and should be monitored closely.97,98,110 (Level of Evidence: A) Class IIa 1. If the risk of morbidity from bleeding outweighs the anticipated benefit afforded by thienopyridine therapy after stent implantation, earlier discontinuation (eg, 12 months) is reasonable. (Level of Evidence: C) (Note: the risk for serious cardiovascular events because of early discontinuation of thienopyridines is greater for patients with drug-eluting stents than those with bare-metal stents.) 2. After PCI, it is reasonable to use 81 mg of aspirin per day in preference to higher maintenance doses.84,85,118 122 (Level of Evidence: B) 3. For patients undergoing coronary artery bypass grafting, clopidogrel (75 mg daily) is a reasonable alternative in patients who are intolerant of or allergic to aspirin. (Level of Evidence: C) Class IIb 1. The benefits of aspirin in patients with asymptomatic peripheral artery disease of the lower extremities are not well established.108,109 (Level of Evidence: B) 2. Combination therapy with both aspirin 75 to 162 mg daily and clopidogrel 75 mg daily may be considered in patients with stable coronary artery disease.112 (Level of Evidence: B) Renin-angiotensin-aldosterone system blockers ACE inhibitors Class I 1. ACE inhibitors should be started and continued indefinitely in all patients with left ventricular ejection fraction 40% and in those with hypertension, diabetes, or chronic kidney disease, unless contraindicated.124,125 (Level of Evidence: A) Class IIa 1. It is reasonable to use ACE inhibitors in all other patients.126 (Level of Evidence: B) ARBs Class I 1. The use of ARBs is recommended in patients who have heart failure or who have had a myocardial infarction with left ventricular ejection fraction 40% and who are ACE-inhibitor intolerant.130 132 (Level of Evidence: A) Class IIa 1. It is reasonable to use ARBs in other patients who are ACE-inhibitor intolerant.133 (Level of Evidence: B) Class IIb 1. The use of ARBs in combination with an ACE inhibitor is not well established in those with systolic heart failure.132,134 (Level of Evidence: A) Aldosterone blockade Class I 1. Use of aldosterone blockade in post myocardial infarction patients without significant renal dysfunction# or hyperkalemia** is recommended in patients who are already receiving therapeutic doses of an ACE inhibitor and -blocker, who have a left ventricular ejection fraction 40%, and who have either diabetes or heart failure.136,137 (Level of Evidence: A) (Continued) Smith et al AHA/ACCF Secondary Prevention: 2011 Update 2461 A) warfarin should be administered.95,99 102 (Level of Evidence: A) (NOTE: Patients receiving low dose aspirin for atherosclerosis should continue to receive it.) ture searches. The recommendations listed in this document are, whenever possible, evidence based. Writing group members performed these relevant supplemental literature searches with key search phrases including but not limited to tobacco/smoking/ smoking cessation; blood pressure control/hypertension; choles- terol/hypercholesterolemia/lipids/lipoproteins/dyslipidemia; physical activity/exercise/exercise training; weight manage- ment/overweight/obesity; type 2 diabetes mellitus manage- ment; antiplatelet agents/anticoagulants; renin/angiotensin/ aldosterone system blockers; b-blockers; influenza vaccination; Table 1. Continued Area for Intervention Recommendations b-Blockers Class I 1. b-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.)138,140,141 (Level of Evidence: A) 2. b-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.139,142,143 (Level of Evidence: B) Class IIa 1. It is reasonable to continue b-blockers beyond 3 years as chronic therapy in all patients with normal left ventricular function who have had myocardial infarction or ACS.139,142,143 (Level of Evidence: B) 2. It is reasonable to give b-blocker therapy in patients with left ventricular systolic dysfunction (ejection fraction #40%) without heart failure or prior myocardial infarction. (Level of Evidence: C) Class IIb 1. b-Blockers may be considered as chronic therapy for all other patients with coronary or other vascular disease. (Level of Evidence: C) Influenza vaccination Class I 1. Patients with cardiovascular disease should have an annual influenza vaccination.144 147 (Level of Evidence: B) Depression Class IIa 1. For patients with recent coronary artery bypass graft surgery or myocardial infarction, it is reasonable to screen for depression if patients have access to case management, in collaboration with their primary care physician and a mental health specialist.148 152 (Level of Evidence: B) Class IIb 1. Treatment of depression has not been shown to improve cardiovascular disease outcomes but may be reasonable for its other clinical benefits. (Level of Evidence: C) Cardiac rehabilitation Class I 1. All eligible patients with ACS or whose status is immediately post coronary artery bypass surgery or post-PCI should be referred to a comprehensive outpatient cardiovascular rehabilitation program either prior to hospital discharge or during the first follow-up office visit.55,154,161,163 (Level of Evidence: A) 2. All eligible outpatients with the diagnosis of ACS, coronary artery bypass surgery or PCI (Level of Evidence: A),55,154,155,161 chronic angina (Level of Evidence: B),161,163 and/or peripheral artery disease (Level of Evidence: A)158,164 within the past year should be referred to a comprehensive outpatient cardiovascular rehabilitation program. 3. A home-based cardiac rehabilitation program can be substituted for a supervised, center-based program for low-risk patients.153,159,160 (Level of Evidence: A) Class IIa 1. A comprehensive exercise-based outpatient cardiac rehabilitation program can be safe and beneficial for clinically stable outpatients with a history of heart failure.159,159a 159c (Level of Evidence: B) JNC indicates the report of the National Heart, Lung, and Blood Institute s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines; ACE, angiotensin-converting enzyme; ATP, Adult Treatment Panel; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; HbA1c, hemoglobin A1c; ACS, acute coronary syndrome; PCI, percutaneous coronary intervention; TIA, transient ischemic attack; INR, international normalized ratio; and ARB, angiotensin receptor blocker. *Presence of established CVD plus (1) multiple major risk factors (especially diabetes), (2) severe and poorly controlled risk factors (especially continued cigarette smoking), (3) multiple risk factors of the metabolic syndrome (especially high triglycerides $200 mg/dL plus non HDL-C $130 mg/dL with low HDL-C ,40 mg/dL), and (4) patients with ACSs. Non HDL-C5total cholesterol minus HDL-C. The use of bile acid sequestrants is relatively contraindicated when triglycerides are $200 mg/dL and is contraindicated when triglycerides are $500 mg/dL. Dietary supplement niacin must not be used as a substitute for prescription niacin. \The combination of high-dose statin plus fibrate (especially gemfibrozil) can increase risk for severe myopathy. Statin doses should be kept relatively low with this combination. Pregnant and lactating women should limit their intake of fish to minimize exposure to methylmercury. #Estimated creatinine clearance should be .30 mL/min. **Potassium should be ,5.0 mEq/L. clinical depression/depression screening; and cardiac/car- diovascular rehabilitation. Additional searches cross- referenced these topics with the subtopics of clinical trials, secondary prevention, atherosclerosis, and coronary/cerebral/pe- ripheral artery disease. These searches were limited to studies, reviews, and other evidence conducted in human subjects and published in English. In addition, the writing group reviewed documents related to the subject matter previ- ously published by the AHA, the ACCF, and the National Institutes of Health. With regard to lipids and dyslipidemias, the lipid reduction trials published between 2002 and 200618,25,166 168 included .50 000 patients and resulted in new optional therapeutic targets, which were outlined in the 2004 update of the National Heart, Lung, and Blood Institute s Adult Treatment Panel (ATP) III report.169 These changes defined optional lower target cho- lesterol levels for very high-risk coronary heart disease (CHD) patients, especially those with acute coronary syndromes, and expanded indications for drug treatment. Subsequent to the 2004 update of ATP III, 2 additional trials26,27 demonstrated cardio- vascular benefit for lipid lowering significantly below current cholesterol goal levels for those with chronic coronary heart disease. These trials allowed for alterations in the 2006 guide- line, such that low-density lipoprotein cholesterol (LDL-C) should be ,100 mg/dL for all patients with CHD and other clinical forms of atherosclerotic disease, but in addition, it is Table 2. Applying Classification of Recommendation and Level of Evidence A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. For comparative effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated. Smith et al AHA/ACCF Secondary Prevention: 2011 Update 2463 reasonable to treat to LDL-C ,70 mg/dL in patients at highest risk. The benefits of lipid-lowering therapy are in proportion to the reduction in LDL-C, and when LDL-C is above 100 mg/dL, an adequate dose of statin therapy should be used to achieve at least a 30% lowering of LDL-C. When the ,70 mg/dL target is chosen, it may be prudent to increase statin therapy in a graded fashion to determine a patient s response and tolerance. Further- more, 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 either statins or LDL-C lowering drug combinations. For patients with triglyceride levels $200 mg/dL, non high-density lipoprotein cholesterol values should be used as a guide to therapy. Although no studies have directly tested treatment to target strategies, the target LDL-C and non HDL-C levels are derived from several randomized controlled trials where the LDL-C levels achieved for patients showing benefit are used to suggest targets. Thus, references for the studies from which targets are derived are listed and targets are considered as level of evidence C. Importantly, this guideline statement for patients with atherosclerotic disease does not modify the recommendations of the 2004 ATP III update for patients without atherosclerotic disease who have diabetes mel- litus or multiple risk factors and a 10-year risk level for CHD .20%. In the latter 2 types of high-risk patients, the recom- mended LDL-C goal of ,100 mg/dL has not changed. Finally, to avoid any misunderstanding about cholesterol management in general, it must be emphasized that a reasonable cholesterol level of ,70 mg/dL does not apply to other types of lower-risk individuals who do not have CHD or other forms of atheroscle- rotic disease; in such cases, recommendations contained in the 2004 ATP III update still pertain. The writing group agreed that no further changes be made in the recommendations for treat- ment of dyslipidemia pending the expected publication of the National Heart, Lung, and Blood Institute s updated ATP guide- lines in 2012. Similar recommendations were made for the treatment of hypertension by the writing group pending the publication of the updated report of the National Heart, Lung, and Blood Institute s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines, expected in the spring of 2012. Trials involving other secondary prevention therapies also have influenced major practice guidelines used to formulate the recommendations in the present update. Thus, specific recom- mendations for clopidogrel use in post acute coronary syndrome or post percutaneous coronary intervention stented patients were included in the 2006 update, and recommendations regard- ing prasugrel and ticagrelor are added to this guideline on the basis of the results of the TRITON-TIMI 38 trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarc- tion) and PLATO (Study of Platelet Inhibition and Patient Outcomes). The present update continues to recommend lower- dose aspirin for chronic therapy. The results of additional studies have further confirmed the benefit of aldosterone antagonist therapy among patients with impaired left ventricular function. The results of several trials involving angiotensin-converting enzyme inhibitor therapy among patients at relatively low risk with stable coronary disease and normal left ventricular function influenced the current recommendations.32 Finally, the recom- mendations for b-blocker therapy have been clarified to reflect the fact that evidence supporting their efficacy is greatest among patients with recent myocardial infarction (,3 years) and/or left ventricular systolic dysfunction (left ventricular ejection fraction #40%). For those patients without these Class I indications, b-blocker therapy is optional (Class IIa or IIb). The writing group confirms the recommendation introduced in 2006 for this guideline with regard to influenza vaccination. According to the US Centers for Disease Control and Prevention, vaccination with inactivated influenza vaccine is recommended for individuals who have chronic disorders of the cardiovascular system because they are at increased risk for complications from influenza.147 Additionally, the writing group added new sections on depression and on cardiovascular rehabilitation. The writing group continues to emphasize the importance of giving consideration to the use of cardiovascular medications that have been proven in randomized clinical trials to be of benefit. This strengthens the evidence-based foundation for therapeutic application of these guidelines. The committee ac- knowledges that ethnic minorities, women, and the elderly are underrepresented in many trials and urges physician and patient participation in trials that will provide additional evidence with regard to therapeutic strategies for these groups of patients. In the 15 years since these guidelines were first published, 2 other developments have made them even more important in clinical care. First, the aging of the population continues to expand the number of patients living with a diagnosis of cardiovascular disease (now estimated at 16.3 million for CHD alone)170 who might benefit from these therapies. Second, multiple studies of the use of these recommended therapies in appropriate patients, although showing slow improvement, continue to support the discouraging conclu- sion that many patients in whom therapies are indicated are not receiving them in actual clinical practice. The AHA and ACCF recommend the use of programs such as the AHA s Get With The Guidelines,171 the American Cancer Society/ American Diabetes Association/AHA s Guideline Advantage Program,172 and the ACC s PINNACLE (Practice INNova- tion And CLinical Excellence) program173 to identify appro- priate patients for therapy, provide practitioners with useful reminders based on the guidelines, and continually assess the success achieved in providing these therapies to the patients who can benefit from them. In this regard, it is important that the healthcare provider not only implement the therapies according to their class of recommendation but also assess for and assist with patient compliance with these therapies in each patient encounter. Discussion of the literature and supporting references for many of the recommendations summarized in the present guideline can be found in greater detail in the upcoming ACCF/AHA guideline for manage- ment of patients undergoing PCI,174 ACCF/AHA guideline for management of patients with peripheral artery dis- ease,175,176 the AHA effectiveness-based guidelines for car- diovascular disease prevention in women,46 and in the AHA/ American Stroke Association guidelines for the prevention of stroke in patients with stroke or transient ischemic attack.123 Finally, the practitioner should exercise judgment in initi- ating the various recommendations if the patient has recently experienced an acute event. Disclosures Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/Advisory Board Other Sidney C. Smith, Jr University of North Carolina None None None None None None None Emelia J. Benjamin Boston University School of Medicine None None None None None None None Robert O. Bonow Northwestern University None None None None None None None Lynne T. Braun Rush University Medical Center NIH-Coinvestigator, Reducing Health Disparity in African American Women: Adherence to Physical Activity* None None None None None None Mark A. Creager Brigham and Women s Hospital Merck ; Sanofi Aventis None None None None Pfizer*; Sanofi Aventis*; Merck (via TIMI group)*; AstraZeneca* None Barry A. Franklin William Beaumont Hospital None None I receive honoraria throughout the year for talks to hospitals (ie, medical grand rounds) and cardiac rehabilitation state associations* None None Smart Balance Scientific Advisory Board* None Raymond J. Gibbons Mayo Clinic King Pharmaceuticals ; TherOx ; VeloMedix None None None None Cardiovascular Clinical Studies*; Medscape (heart.org)*; Molecular Insight Pharmaceuticals*; TherOx*; Lantheus Medical Imaging* None Scott M. Grundy UT Southwestern Medical Center Sankyo Perot Foundation None None None AstraZeneca*; Merck*; Merck/Schering- Plough*; Pfizer* (Relationships ended 3 years ago) None Loren F. Hiratzka Cardiovascular and Thoracic Surgeons/ Tri-Health Inc None None None None None None None Daniel W. Jones University of Mississippi None None None None None None None Donald M. Lloyd-Jones Northwestern None None None None None None None Margo Minissian Cedars Sinai Medical Center RWise Study, Co-Investigator, Gilead Sciences None None None None None None Lori Mosca Columbia University NIH* None None None None Advise & Consent, Inc.*; Gilead Science*; Rowpar Pharmaceuticals, Inc. ; Sanofi-Aventis* None Eric D. Peterson Duke University Medical Center Bristol-Myers Squibb/Sanofi ; Eli Lilly ; Merck/Schering-Plough ; Johnson & Johnson None None None None None None Ralph L. Sacco University of Miami NINDS Northern Manhattan Study* None None None None Boehringer Ingelheim* (ended March 2009); GlaxoSmithKline (ended March 2009)*; Sanofi Aventis* (ended March 2009); DSMB (Atrial Fibrillation Trial institutionally sponsored by Population Health Research Institute at McMaster University, Hamilton, Ontario)* None (Continued) Smith et al AHA/ACCF Secondary Prevention: 2011 Update 2465 Writing Group Disclosures, Continued Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/Advisory Board Other John Spertus Mid America Heart Institute Amgen ; Bristol-Myers Squibb/Sanofi ; Eli Lilly ; Cordis ; NIH ; ACCF ; AHA Atherotech ; Roche Diagnostics None None Holds copyright to Kansas City Cardiomyopathy Questionnaire ; holds copyright to Peripheral Artery Questionnaire*; holds copyright to Seattle Angina Questionnaire St. Jude Medical*; United HealthCare*; Amgen* None James H. Stein University of Wisconsin School of Medicine and Public Health Sanofi-Aventis (ended July 2009); Siemens Medical Solutions (ended July 2009); SonoSite (ended None Abbott* and Takeda* (no permanent remuneration; all money to charity. Both were terminated None None Abbott,* Lilly,* and Takeda* (research trial DSMBs) Takeda* (training grant to institution ended June 2009); Wisconsin Alumni Research Foundation* (royalties related to carotid ultrasound and cardiovascular disease risk prediction) Kathryn A. Taubert World Heart Federation None None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be significant if (1) the person receives $10 000 or more during any 12-month period, or 5% or more of the person s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. Reviewer Disclosures Reviewer Employment Research Grant Other Research Support Speakers Bureau/Honoraria Expert Witness Ownership Interest Consultant/Advisory Board Other Elliott M. Antman Brigham & Women s Hospital None None None None None None None Jeffrey L. Anderson Intermountain Medical Center None None None None None AstraZeneca* None Gary J. Balady Boston Medical Center None None None None None None None Eric R. Bates University of Michigan None None None None None AstraZeneca*; Daiichi Sankyo*; Eli Lilly*; Merck*; Sanofi Aventis* None Vera Bittner University of Alabama at Birmingham Clinical site PI for multicenter trials funded by: Roche/Genentech ; Gilead; GSK ; NIH/Abbott ; NIH/Yale None None None None Roche/Genentech*; Amarin*; Pfizer* None Ann F. Bolger University of California, San Francisco None None None None None None None Victor A. Ferrari University of Pennsylvania None None None None None Board of Trustees, Society for Cardiovascular Magnetic Resonance (no monetary value)*; Editorial Board, Journal of Cardiovascular Magnetic Resonance (no monetary value)* None Stephan Fihn Department of Veterans Affairs and University of Washington None None None None None None None Gregg Fonarow UCLA NHLBI ; AHRQ None None None None Novartis ; Medtronic* None Federico Gentile Centro Medico diagnostic, Naples-Italy None None None None None None None Larry B. Goldstein Duke University None None None None None None None Jonathan Halperin Mount Sinai Medical Center, New York, NY None None None None None Boehringer Ingelheim ; Astellas Pharma, US*; Bristol-Meyers Squibb*; Daiichi Sankyo*; Johnson & Johnson*; Pfizer, Inc*; Sanofi-Aventis* None (Continued) References 1. Smith SC Jr, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, Mosca L, Pasternak RC, Pearson T, Pfeffer MA, Taubert KA. AHA/ACC guidelines for secondary prevention for patients with coronary and other athero- sclerotic vascular disease: 2006 update: [published correction appears in Circulation. 2006;113:e847]. Circulation. 2006;113:2363 2372. 2. Rothemich SF, Woolf SH, Johnson RE, Burgett AE, Flores SK, Marsland DW, Ahluwalia JS. Effect on cessation counseling of docu- menting smoking status as a routine vital sign: an ACORN study. Ann Fam Med. 2008;6:60 68. 3. Rosser A, McDowvell I, Newvell C. Documenting smoking status: trial of three strategies. Can Fam Physician. 1992;38:1623 1628. 4. US Department of Health and Human Services. Systems Change: Treating Tobacco Use and Dependence. Based on the Public Health Service (PHS) Clinical Practice Guideline 2008 Update. www.ahrq. gov/clinic/tobacco/systems.htm. Accessed September 25, 2011. 5. Cummings SR, Coates TJ, Richard RJ, Hansen B, Zahnd EG, Van- derMartin R, Duncan C, Gerbert B, Martin A, Stein MJ. Training physicians in counseling about smoking cessation: a randomized trial of the Quit for Life program. Ann Intern Med. 1989;110:640 647. 6. Cummings SR, Richard RJ, Duncan CL, Hansen B, Vander Martin R, Gerbert B, Coates TJ. Training physicians about smoking cessation: a controlled trial in private practice. J Gen Intern Med. 1989;4:482 489. 7. Fiore MC, Jae n CR, Baker TB, Bailey WC, Benowitz NL, Curry SJ, Dorfman SF, Froelicher ES, Goldstein MG, Healton CG, Henderson PN, Heyman RB, Koh HK, Kottke TE, Lando HA, Mecklenburg RE, Mer- melstein RJ, Mullen PD, Orleans CT, Robinson L, Stitzer ML, Tom- masello AC, Villejo L, Wewers ME . Treating Tobacco Use and Depen- dence: 2008 Update. Clinical Practice Guideline. Rockville, MD: US Department of Health and Human Services, Public Health Service; May use08.pdf. Accessed December 9, 2010. 8. Duncan C, Stein MJ, Cummings SR. Staff involvement and special follow-up time increase physicians counseling about smoking ces- sation: a controlled trial. Am J Public Health. 1991;81:899 901. 9. Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE; Lung Health Study Research Group. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med. 2005;142:233 239. 10. US Department of Health and Human Services. The Health Conse- quences of Involuntary Exposure to Tobacco Smoke: A Report From the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2006. 11. Committee on Secondhand Smoke Exposure and Acute Coronary Events, Institute of Medicine. Secondhand Smoke Exposure and Car- diovascular Effects: Making Sense of the Evidence. Washington, DC: National Academies Press; 2010. http://www.nap.edu/catalog/12649. html. Accessed May 31, 2011. 12. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; and the National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Pre- vention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206 1252. 13. Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin PH, Karanja N. A clinical trial of the effects of dietary patterns on blood pressure: DASH Collaborative Research Group. N Engl J Med. 1997;336: 1117 1124. 14. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med. 2001;344:3 10. 15. Appel LJ, Frohlich ED, Hall JE, Pearson TA, Sacco RL, Seals DR, Sacks FM, Smith SC Jr, Vafiadis DK, Van Horn LV. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke: a call to action from the American Heart Association. Circulation. 2011;123:1138 1143. 16. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002;136:493 503. Reviewer Disclosures, Continued Reviewer Employment Research Grant Other Research Support Speakers Bureau/Honoraria Expert Witness Ownership Interest Consultant/Advisory Board Other Courtney Jordan University of Minnesota None None None None None None None Noel Bairey Merz Cedars-Sinai Medical Center Gilead NHLBI Mayo Foundation*; SCS Healthcare ; Practice Point Communications*; Inst for Professional Education*; Medical Education Speakers Network*; Minneapolis Heart Institute*; Catholic Healthcare West*; Novant Health*; HealthScience Media Inc*; Huntsworth Health*; WomenHeart Coalition*; Los Robles Medical Center*; Monterrey Community Hospital (honorarium, donated to ACC)*; Los Angeles OB-GYN Society*; Pri-Med*; North American Menopause Society* None Medtronic UCSF*; Society for Women s Health Research*; Interquest*; Dannemiller*; Navvis & Co*; Springer SBM LLC*; Duke*; NHLBI*; Italian National Institutes of Health*; Gilead* None L. Kristin Newby Duke University None None None None None None None Patrick O Gara Brigham & Women s Hospital None None None None None Lantheus Medical Imaging* None Thomas W. Rooke Mayo Clinic None None None None None Merck Adjudication (Event) Committee* None Vincent Sorrell University of Arizona None None Lantheus Medical Imaging None None None None This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be significant if (1) the person receives $10 000 or more during any 12-month period, or 5% or more of the person s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. Smith et al AHA/ACCF Secondary Prevention: 2011 Update 2467 17. SHEP Cooperative Research Group. Prevention of stroke by antihyper- tensive drug treatment in older persons with isolated systolic hyper- tension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265:3255 3264. 18. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) [published cor- rections appear in JAMA. 2004;291:2196 and JAMA. 2003;289:178]. JAMA. 2002;288:2981 2997. 19. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56: 320 328. 20. Murphy SA, Cannon CP, Wiviott SD, McCabe CH, Braunwald E. Reduction in recurrent cardiovascular events with intensive lipid- lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndrome: from the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Throm- bolysis In Myocardial Infarction 22) trial. J Am Coll Cardiol. 2009;54: 2358 2362. 21. Ginsberg HN, Kris-Etherton P, Dennis B, Elmer PJ, Ershow A, Lefevre M, Pearson T, Roheim P, Ramakrishnan R, Reed R, Stewart K, Stewart P, Phillips K, Anderson N. Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1. Arterioscler Thromb Vasc Biol. 1998;18:441 449. 22. Schaefer EJ, Lamon-Fava S, Ausman LM, Ordovas JM, Clevidence BA, Judd JT, Goldin BR, Woods M, Gorbach S, Lichtenstein AH. Individual variability in lipoprotein cholesterol response to National Cholesterol Education Program Step 2 diets. Am J Clin Nutr. 1997;65:823 830. 23. Schaefer EJ, Lichtenstein AH, Lamon-Fava S, Contois JH, Li Z, Ras- mussen H, McNamara JR, Ordovas JM. Efficacy of a National Choles- terol Education Program Step 2 diet in normolipidemic and hypercho- lesterolemic middle-aged and elderly men and women. Arterioscler Thromb Vasc Biol. 1995;15:1079 1085. 24. Yu-Poth S, Zhao G, Etherton T, Naglak M, Jonnalagadda S, Kris- Etherton PM. Effects of the National Cholesterol Education Program s Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis. Am J Clin Nutr. 1999;69:632 646. 25. MRC/BHF Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7 22. 26. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorva- statin in patients with stable coronary disease. N Engl J Med. 2005;352: 1425 1435. 27. Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, Larsen ML, Bendiksen FS, Lindahl C, Szarek M, Tsai J; Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Study Group. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial [published correction appears in JAMA. 2005;294:3092]. JAMA. 2005;294:2437 2445. 28. Cholesterol Treatment Trialists (CTT) Collaborators; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intense lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670 1681. 29. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Edu- cation Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143 3421. 30. Robinson JG, Wang S, Smith BJ, Jacobson TA. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J Am Coll Cardiol. 2009;53:316 322. 31. Zhao XQ, Brown BG, Hillger L, Sacco D, Bisson B, Fisher L, Albers JJ. Effects of intensive lipid-lowering therapy on the coronary arteries of asymptomatic subjects with elevated apolipoprotein B. Circulation. 1993;88:2744 2753. 32. Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P, Frohlich J, Albers JJ. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583 1592. 33. Campeau L, Hunninghake DB, Knatterud GL, White CW, Domanski M, Forman SA, Forrester JS, Geller NL, Gobel FL, Herd JA, Hoogwerf BJ, Rosenberg Y; and Post CABG Trial Investigators. Aggressive choles- terol lowering delays saphenous vein graft atherosclerosis in women, the elderly, and patients with associated risk factors: NHLBI post coronary artery bypass graft clinical trial. Circulation. 1999;99:3241 3247. 34. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J; Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipo- protein cholesterol. N Engl J Med. 1999;341:410 418. 35. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8:1245 1255. 36. The Lipid Research Clinics Coronary Primary Prevention Trial results, I: reduction in incidence of coronary heart disease. JAMA. 1984;251: 351 364. 37. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorva- statin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes [published correction appears in N Engl J Med. 2006;354:778]. N Engl J Med. 2004;350: 1495 1504. 38. Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta- analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol. 2006;48:438 445. 39. Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Manninen V, Ma enjpa a H, Ma lko nen M, Ma ntta ri M, Norola S, Pasternack A, Pikkarainen J, Romo M, Sjo blom T, Nikkila EA. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317:1237 1245. 40. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, Drury P, Kesa niemi YA, Sullivan D, Hunt D, Colman P, d Emden M, Whiting M, Ehnholm C, Laakso M; FIELD Study Investigators. Effects of long-term fenofibrate therapy on cardio- vascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial [published corrections appear in 1849 1861. 41. Robins SJ, Rubins HB, Faas FH, Schaefer EJ, Elam MB, Anderson JW, Collins D; Veterans Affairs HDL Intervention Trial (VA-HIT). Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). Diabetes Care. 2003;26:1513 1517. 42. LaRosa JC, Grundy SM, Kastelein JJ, Kostis JB, Greten H; Treating to New Targets (TNT) Steering Committee and Investigators. Safety and efficacy of atorvastatin-induced very low-density lipoprotein cholesterol levels in patients with coronary heart disease (a post hoc analysis of the Treating to New Targets [TNT] study). Am J Cardiol. 2007;100: 747 752. 43. Hayward RA, Krumholz HM, Zulman DM, Timbie JW, Vijan S. Opti- mizing statin treatment for primary prevention of coronary artery disease [published correction appears in Ann Intern Med. 2011;154:848]. Ann Intern Med. 2010;152:69 77. 44. Kris-Etherton PM, Harris WS, Appel LJ; for the Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease [published correction appears in Circulation. 2003;107:512]. Circulation. 2002;106:2747 2757. 45. Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2002;112:298 304. 46. Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Pin a IL, Roger VL, Shaw LJ, Zhao D, Beckie TM, Bushnell C, D Armiento J, Kris-Etherton PM, Fang J, Ganiats TG, Gomes AS, Gracia CR, Haan CK, Jackson EA, Judelson DR, Kelepouris E, Lavie CJ, Moore A, Nussmeier NA, Ofili E, Oparil S, Ouyang P, Pinn VW, Sherif K, Smith SC Jr, Sopko G, Chandra-Strobos N, Urbina EM, Vaccarino V, Wenger NK. Effectiveness-based guidelines for the pre- vention of cardiovascular disease in women: 2011 update: a guideline from the American Heart Association [published correction appears in Circulation. 2011;123:e624]. Circulation 2011;123:1243 1262. 47. Balady GJ, Williams MA, Ades PA, Bittner V, Comoss P, Foody JM, Franklin B, Sanderson B, Southard D. Core components of cardiac rehabilitation/secondary prevention programs: 2007 update: a scientific statement from the American Heart Association Exercise, Cardiac Reha- bilitation, and Prevention Committee, the Council on Clinical Car- diology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation. 2007;115:2675 2682. 48. Mark DB, Hlatky MA, Harrell FE Jr, Lee KL, Califf RM, Pryor DB. Exercise treadmill score for predicting prognosis in coronary artery disease. Ann Intern Med. 1987;106:793 800. 49. Mark DB, Shaw L, Harrell FE Jr, Hlatky MA, Lee KL, Bengtson JR, McCants CB, Califf RM, Pryor DB. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med. 1991;325:849 853. 50. Vanhees L, Fagard R, Thijs L, Staessen J, Amery A. Prognostic signif- icance of peak exercise capacity in patients with coronary artery disease. J Am Coll Cardiol. 1994;23:358 363. 51. Kavanagh T, Mertens DJ, Hamm LF, Beyene J, Kennedy J, Corey P, Shephard RJ. Prediction of long-term prognosis in 12 169 men referred for cardiac rehabilitation. Circulation. 2002;106:666 671. 52. Kavanagh T, Mertens DJ, Hamm LF, Beyene J, Kennedy J, Corey P, Shephard RJ. Peak oxygen intake and cardiac mortality in women referred for cardiac rehabilitation. J Am Coll Cardiol. 2003;42: 2139 2143. 53. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van HL, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm LH, Sorlie P, Yancy CW, Rosamond WD. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association s Strategic Impact Goal through 2020 and beyond. Circulation. 2010;121:586 613. 54. 2008 Physical Activity Guidelines for Americans. Washington, DC: US Department of Health and Human Services; 2008. 55. Taylor RS, Brown A, Ebrahim S, Jolliffe J, Noorani H, Rees K, Skidmore B, Stone JA, Thompson DR, Oldridge N. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med. 2004;116: 682 692. 56. Marwick TH, Hordern MD, Miller T, Chyun DA, Bertoni AG, Blu- menthal RS, Philippides G, Rocchini A; on behalf of the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Com- mittee of the Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; Council on Nutrition, Physical Activity, and Metabolism; and the Interdisciplinary Council on Quality of Care and Outcomes Research. Exercise training for type 2 diabetes mellitus: impact on cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009;119: 3244 3262. 57. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology/American Heart Asso- ciation Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myo- cardial Infarction) [published correction appears in Circulation. 2005; 111:2013]. Circulation. 2004;110:588 636. 58. Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD, Bauman A. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Asso- ciation. Circulation. 2007;116:1081 1093. 59. Williams MA, Haskell WL, Ades PA, Amsterdam EA, Bittner V, Franklin BA, Gulanick M, Laing ST, Stewart KJ. Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2007;116:572 584. 60. National Institutes of Health; National Heart, Lung, and Blood Institute. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; obesity/ob_gdlns.pdf. Accessed October 3, 2011. 61. Klein S, Burke LE, Bray GA, Blair S, Allison DB, Pi-Sunyer X, Hong Y, Eckel RH. Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from the American Heart Association Council on Nutrition, Physical Activity, and Metab- olism. Circulation. 2004;110:2952 2967. 62. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement [published corrections appear in Circulation. 2005;112:e297 and Circulation. 2005;112:e298]. Circulation. 2005;112:2735 2752. 63. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK. ACC/AHA guidelines for the management of patients with ST-evaluation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction) [published corrections appear in Circulation. 2005;111:2013 2014, Cir- culation. 2007;115:e411, and Circulation. 2010;121:e441]. Circulation. 2004;110:e82 e292. 64. Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, Ferguson TB Jr, Fihn SD, Fraker TD Jr, Gardin JM, O Rourke RA, Pasternak RC, Williams SV, Gibbons RJ, Alpert JS, Antman EM, Hiratzka LF, Fuster V, Faxon DP, Gregoratos G, Jacobs AK, Smith SC Jr. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). Circulation. 2003;107:149 158. 65. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341:1097 1105. 66. Jensen MK, Chiuve SE, Rimm EB, Dethlefsen C, Tj nneland A, Joensen AM, Overvad K. Obesity, behavioral lifestyle factors, and risk of acute coronary events. Circulation. 2008;117:3062 3069. 67. Arnlo v J, Ingelsson E, Sundstro m J, Lind L. Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation. 2010;121:230 236. 68. Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol. 2009;53:1925 1932. 69. Gruberg L, Weissman NJ, Waksman R, Fuchs S, Deible R, Pinnow EE, Ahmed LM, Kent KM, Pichard AD, Suddath WO, Satler LF, Lindsay J Jr. The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox? J Am Coll Cardiol. 2002;39:578 584. 70. Jacobs EJ, Newton CC, Wang Y, Patel AV, McCullough ML, Campbell PT, Thun MJ, Gapstur SM. Waist circumference and all-cause mortality in a large U.S. cohort. Arch Intern Med. 2010;170:1293 1301. 71. Skyler JS, Bergenstal R, Bonow RO, Buse J, Deedwania P, Gale EAM, Howard BV, Kirkman MS, Kosiborod M, Reaven P, Sherwin RS. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association [published correction appears in Circulation. 2009;119:e605]. Circulation. 2009;119:351 357. 72. Kelly TN, Bazzano LA, Fonseca VA, Thethi TK, Reynolds K, He J. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med. 2009;151:394 403. 73. Kaul S, Bolger AF, Herrington D, Giugliano RP, Eckel RH. Thiazoli- dinedione drugs and cardiovascular risks: a science advisory from the American Heart Association and the American College of Cardiology Foundation. Circulation. 2010;121:1868 1877. 74. American Diabetes Association. Standards of medical care in diabetes: 2011. Diabetes Care. 2011;34(suppl 1):S11 S61. Smith et al AHA/ACCF Secondary Prevention: 2011 Update 2469 75. Selvin E, Bolen S, Yeh H-C, Wiley C, Wilson LM, Marinopoulos SS, Feldman L, Vassy J, Wilson R, Bass EB, Brancati FL. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med. 2008;168:2070 2080. 76. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) [published correction appears in Lancet.1998;352:1558]. Lancet. 1998;352:854 865. 77. TurnbullFM, Abraira C, Anderson RJ, Byington RP, Chalmers JP, Duckworth WC, Evans GW, Gerstein HC, Holman RR, Moritz TE, Neal BC, Ninomiya T, Patel AA, Paul SK, Travert F, Woodward M; Control Group. Intensive glucose control and macrovascular outcomes in type 2 diabetes [published correction appears in Diabetologia. 2009;52:2470]. Diabetologia. 2009;52:2288 2298. 78. Ray KK, Seshasai SR, Wijesuriya S, Sivakumaran R, Nethercott S, Preiss D, Erqou S, Sattar N. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009;373: 1765 1772. 79. Currie CJ, Peters JP, Tynan A, Evans M, Heine RJ, Bracco OL, Zagar T, Poole CD. Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. Lancet. 2010;375:481 489. 80. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577 1589. 81. Becker RC, Meade TW, Berger PB, Ezekowitz M, O Connor CM, Vorchheimer DA, Guyatt GH, Mark DB, Harrington RA; American College of Chest Physicians. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133:776S 814S. 82. Antithrombotic Trialists (ATT) Collaboration; Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A. Aspirin in the primary and secondary prevention of vascular disease: collab- orative meta analysis of individual participant data from randomised trials. Lancet. 2009;373:1849 1860. 83. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation [pub- lished corrections appear in N Engl J Med. 2001;345:1506 and N Engl J Med. 2001;345:1716]. N Engl J Med. 2001;345:494 502. 84. 