Prevention of cardiovascular disease events in those with established disease or at high risk
- Charles H Hennekens, MD, DrPH
Charles H Hennekens, MD, DrPH
- First Sir Richard Doll Professor & Senior Academic Advisor to the Dean, Charles E. Schmidt College of Medicine, Florida Atlantic University
- Clinical Professor, Nova Southeastern University
- Voluntary Professor, University of Miami Miller School of Medicine, Meharry Medical College, and Baylor Colle
- Jose Lopez-Sendon, MD, PhD
Jose Lopez-Sendon, MD, PhD
- Chief, Cardiology Department
- Hospital Universitario La Paz
- Instituto de Investigación La PAZ
- Section Editors
- Christopher P Cannon, MD
Christopher P Cannon, MD
- Section Editor — Coronary Heart Disease
- Professor of Medicine
- Harvard Medical School
- Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
- Section Editor — Coronary Heart Disease
- Professor of Cardiovascular Science
- Director, Cardiovascular and Cell Sciences Research Institute
- St. George's, University of London
Patients with established cardiovascular disease (CVD) have a high risk of subsequent cardiovascular events, including myocardial infarction (MI), stroke, and death. Therapeutic lifestyle changes (TLCs) such as increased physical activity, dietary modification/weight loss, and smoking cessation are of proven benefit and are likely to improve outcomes beginning within a matter of months. Adjunctive drug therapies of proven benefit are principally aspirin and statins and in patients with MI or heart failure, they include beta blockers and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. TLCs and adjunctive drug therapies of proven benefit are likely to have additive benefits in the secondary as well as primary prevention of CVD.
Other individuals without established CVD are also at high risk of cardiovascular events and include individuals with multiple traditional risk factors for CVD or patients with chronic kidney disease.
Interventions to prevent CVD events in those with established disease or at high risk will be summarized here. More detailed discussions of each risk factor are presented elsewhere. (See "Overview of primary prevention of coronary heart disease and stroke".)
ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
All patients with established cardiovascular disease (CVD) including coronary heart disease, cerebrovascular disease, and peripheral artery disease should receive interventions to prevent a subsequent CVD event [1-3]. These are termed secondary preventive interventions. All healthcare providers should attempt to lower the risk of a subsequent event in all patients with CVD using therapeutic lifestyle changes as well as adjunctive drug therapies of proven benefit.
PATIENTS AT HIGH RISK
We define patients at high risk as those with a prior CVD event as well as those whose 10-year risk is >10 percent. These latter subjects are likely to include most patients with diabetes, and those with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) <45 mL/min/per 1.73 m2 as well as many with metabolic syndrome, the constellation of abdominal obesity, hypertension, diabetes, and dyslipidemia, which is also called the insulin resistance syndrome. In all subjects without a prior CVD event, preventive interventions are labelled as primary. (See "Estimation of cardiovascular risk in an individual patient without known cardiovascular disease" and "The metabolic syndrome (insulin resistance syndrome or syndrome X)", section on 'Prevalence and risk factors'.)
- Smith SC Jr, Benjamin EJ, Bonow RO, et al. 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.
- Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129:S76.
- Perk J, De Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012; 33:1635.
- Patel UD, Young EW, Ojo AO, Hayward RA. CKD progression and mortality among older patients with diabetes. Am J Kidney Dis 2005; 46:406.
- Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129:S1.
- LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352:1425.
- Bucher HC, Griffith LE, Guyatt GH. Effect of HMGcoA reductase inhibitors on stroke. A meta-analysis of randomized, controlled trials. Ann Intern Med 1998; 128:89.
- Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials. JAMA 1997; 278:313.
- Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010; 376:1670.
- Hennekens CH, Breuer NR, Gelb IJ, et al. Emerging clinical challenges in the use of statins. Am J Med 2013; 126:663.
- Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350:1495.
- Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372:2387.
- Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352:20.
- Morrow DA, de Lemos JA, Sabatine MS, et al. Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial. Circulation 2006; 114:281.
- Bohula EA, Giugliano RP, Cannon CP, et al. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation 2015; 132:1224.
- Ballantyne CM, Olsson AG, Cook TJ, et al. Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation 2001; 104:3046.
- Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366:1267.
- Mora S, Wenger NK, Demicco DA, et al. Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study. Circulation 2012; 125:1979.
- Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction. www.acc.org/qualityandscience/clinical/statements.htm (Accessed on August 24, 2006).
- Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289:2560.
- www.acc.org/qualityandscience/clinical/statements.htm (Accessed on September 18, 2007). www.acc.org/qualityandscience/clinical/statements.htm (Accessed on September 18, 2007).
- Iestra JA, Kromhout D, van der Schouw YT, et al. Effect size estimates of lifestyle and dietary changes on all-cause mortality in coronary artery disease patients: a systematic review. Circulation 2005; 112:924.
- Chow CK, Jolly S, Rao-Melacini P, et al. Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes. Circulation 2010; 121:750.
- Chow CK, Redfern J, Hillis GS, et al. Effect of Lifestyle-Focused Text Messaging on Risk Factor Modification in Patients With Coronary Heart Disease: A Randomized Clinical Trial. JAMA 2015; 314:1255.
- Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: a systematic review. JAMA 2003; 290:86.
- Rea TD, Heckbert SR, Kaplan RC, et al. Smoking status and risk for recurrent coronary events after myocardial infarction. Ann Intern Med 2002; 137:494.
- Krauss RM, Winston M, Fletcher RN, Grundy SM. Obesity: impact of cardiovascular disease. Circulation 1998; 98:1472.
- Willett WC, Manson JE, Stampfer MJ, et al. Weight, weight change, and coronary heart disease in women. Risk within the 'normal' weight range. JAMA 1995; 273:461.
- Manson JE, Willett WC, Stampfer MJ, et al. Body weight and mortality among women. N Engl J Med 1995; 333:677.
- Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med 2002; 347:305.
- Stevens VJ, Corrigan SA, Obarzanek E, et al. Weight loss intervention in phase 1 of the Trials of Hypertension Prevention. The TOHP Collaborative Research Group. Arch Intern Med 1993; 153:849.
- van Dam RM, Rimm EB, Willett WC, et al. Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med 2002; 136:201.
- Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995; 122:481.
- Clark AM, Hartling L, Vandermeer B, McAlister FA. Meta-analysis: secondary prevention programs for patients with coronary artery disease. Ann Intern Med 2005; 143:659.
- Muntwyler J, Hennekens CH, Buring JE, Gaziano JM. Mortality and light to moderate alcohol consumption after myocardial infarction. Lancet 1998; 352:1882.
- Knoops KT, de Groot LC, Kromhout D, et al. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 2004; 292:1433.
- Task Force Members, Montalescot G, Sechtem U, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34:2949.
- Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; 368:1279.
- Montori VM, Devereaux PJ, Adhikari NK, et al. Randomized trials stopped early for benefit: a systematic review. JAMA 2005; 294:2203.
- Bassler D, Briel M, Montori VM, et al. Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA 2010; 303:1180.
- Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines 6. Rating the quality of evidence--imprecision. J Clin Epidemiol 2011; 64:1283.
- Dehghan M, Mente A, Teo KK, et al. Relationship between healthy diet and risk of cardiovascular disease among patients on drug therapies for secondary prevention: a prospective cohort study of 31 546 high-risk individuals from 40 countries. Circulation 2012; 126:2705.
- Li S, Chiuve SE, Flint A, et al. Better diet quality and decreased mortality among myocardial infarction survivors. JAMA Intern Med 2013; 173:1808.
- Lau HL, Kwong JS, Yeung F, et al. Yoga for secondary prevention of coronary heart disease. Cochrane Database Syst Rev 2012; 12:CD009506.
- Authors/Task Force Members, Rydén L, Grant PJ, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013; 34:3035.
- Standards of Medical Care in Diabetes-2016: Summary of Revisions. Diabetes Care 2016; 39 Suppl 1:S4.
- Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71.
- Malmberg K, Norhammar A, Wedel H, Rydén L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. Circulation 1999; 99:2626.
- Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; 354:1706.
- Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012; 366:1404.
- Scirica BM, Bonaca MP, Braunwald E, et al. Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial. Lancet 2012; 380:1317.
- Cavender MA, Scirica BM, Bonaca MP, et al. Vorapaxar in patients with diabetes mellitus and previous myocardial infarction: findings from the thrombin receptor antagonist in secondary prevention of atherothrombotic ischemic events-TIMI 50 trial. Circulation 2015; 131:1047.
- Warfarin Antiplatelet Vascular Evaluation Trial Investigators, Anand S, Yusuf S, et al. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med 2007; 357:217.
- Anand SS, Yusuf S. Oral anticoagulants in patients with coronary artery disease. J Am Coll Cardiol 2003; 41:62S.
- AHA, ACC, National Heart, Lung, and Blood Institute, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol 2006; 47:2130.
- DREAM Trial Investigators, Bosch J, Yusuf S, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med 2006; 355:1551.
- Gurfinkel EP, Leon de la Fuente R, Mendiz O, Mautner B. Flu vaccination in acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) Study. Eur Heart J 2004; 25:25.
- Naghavi M, Barlas Z, Siadaty S, et al. Association of influenza vaccination and reduced risk of recurrent myocardial infarction. Circulation 2000; 102:3039.
- Phrommintikul A, Kuanprasert S, Wongcharoen W, et al. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. Eur Heart J 2011; 32:1730.
- Udell JA, Zawi R, Bhatt DL, et al. Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis. JAMA 2013; 310:1711.
- Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342:154.
- Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999; 354:447.
- Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360:23.
- Cook NR, Albert CM, Gaziano JM, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study. Arch Intern Med 2007; 167:1610.
- Crittenden DB, Lehmann RA, Schneck L, et al. Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout. J Rheumatol 2012; 39:1458.
- Langevitz P, Livneh A, Neumann L, et al. Prevalence of ischemic heart disease in patients with familial Mediterranean fever. Isr Med Assoc J 2001; 3:9.
- Nidorf M, Thompson PL. Effect of colchicine (0.5 mg twice daily) on high-sensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease. Am J Cardiol 2007; 99:805.
- Hemkens LG, Ewald H, Gloy VL, et al. Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis. Heart 2016; 102:590.
- Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol 2013; 61:404.
- Lamas GA, Goertz C, Boineau R, et al. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. JAMA 2013; 309:1241.
- Nissen SE. Concerns about reliability in the Trial to Assess Chelation Therapy (TACT). JAMA 2013; 309:1293.
- Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2014; 64:1929.
- Rosenson RS, Hurt-Camejo E. Phospholipase A2 enzymes and the risk of atherosclerosis. Eur Heart J 2012; 33:2899.
- Nicholls SJ, Kastelein JJ, Schwartz GG, et al. Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial. JAMA 2014; 311:252.
- STABILITY Investigators, White HD, Held C, et al. Darapladib for preventing ischemic events in stable coronary heart disease. N Engl J Med 2014; 370:1702.
- O'Donoghue ML, Braunwald E, White HD, et al. Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial. JAMA 2014; 312:1006.
- Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012; 126:3097.
- Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012; 126:e354.
- Bhatt DL, Flather MD, Hacke W, et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol 2007; 49:1982.
- Pfeffer MA, Jarcho JA. The charisma of subgroups and the subgroups of CHARISMA. N Engl J Med 2006; 354:1744.
- ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
- PATIENTS AT HIGH RISK
- Diabetes mellitus
- Chronic kidney disease
- Older adults
- MULTIPLE RISK FACTOR INTERVENTION
- Initial therapy in stable patients
- LDL-C goal
- After an acute coronary syndrome
- Patients for whom statin monotherapy is insufficient
- Possible role of CRP
- HDL-cholesterol and triglycerides
- Residual risk
- LIFESTYLE MODIFICATION
- Cardiac rehabilitation programs
- Text messaging
- Smoking cessation
- Weight reduction
- Physical activity
- OTHER ADJUNCTIVE THERAPIES
- Antithrombotic therapy
- - Antiplatelet therapy
- - Anticoagulant therapy
- Beta blockers
- ACE inhibitors or ARBs
- Aldosterone blockade
- Influenza vaccination
- Fish oil and marine omega-3 fatty acids
- Therapies without well established benefit
- PATIENT EDUCATION
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS