Cardiovascular disease and risk management: Standards of medical care in diabetes- 2020

Diabetes Care

Volumn 43, Issue , 2020, Pages S111-S134

[No Author Info available]

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ALBIGLUTIDE; ALIROCUMAB; ANGIOTENSIN RECEPTOR ANTAGONIST; CALCIUM CHANNEL BLOCKING AGENT; CANAGLIFLOZIN; CLOPIDOGREL; DAPAGLIFLOZIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EMPAGLIFLOZIN; EVOLOCUMAB; EXENDIN 4; EZETIMIBE; FENOFIBRATE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ICOSAPENTAENOIC ACID; INDAPAMIDE PLUS PERINDOPRIL; LABETALOL; LAROPIPRANT PLUS NICOTINIC ACID; LIRAGLUTIDE; LIXISENATIDE; METHYLDOPA; NIFEDIPINE; PRASUGREL; SEMAGLUTIDE; SIMVASTATIN; THIAZIDE DIURETIC AGENT; TICAGRELOR;

ACUTE KIDNEY FAILURE; ALBUMINURIA; ARTICLE; BEDTIME DOSAGE; BLOOD PRESSURE MONITORING; BLOOD PRESSURE REGULATION; CALORIC INTAKE; CARDIOVASCULAR RISK; CHRONIC KIDNEY FAILURE; CLINICAL PRACTICE; COGNITION; CORONARY ARTERY ATHEROSCLEROSIS; DIASTOLIC BLOOD PRESSURE; DIET RESTRICTION; DISEASE SEVERITY; DYSLIPIDEMIA; FAMILY HISTORY; HEALTH CARE QUALITY; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART FAILURE WITH REDUCED EJECTION FRACTION; HIGH RISK PATIENT; HUMAN; HYPERKALEMIA; HYPERTENSION; INCIDENCE; INSULIN DEPENDENT DIABETES MELLITUS; LIFESTYLE MODIFICATION; LOW DRUG DOSE; MATERNAL HYPERTENSION; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PHYSICAL ACTIVITY; PRACTICE GUIDELINE; PREVALENCE; PRIMARY PREVENTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK ASSESSMENT; RISK MANAGEMENT; RISK REDUCTION; SECONDARY PREVENTION; SMOKING; SODIUM INTAKE; SYSTOLIC BLOOD PRESSURE; TREATMENT DURATION; TREATMENT OUTCOME; CARDIOVASCULAR DISEASE; DIABETES MELLITUS; DIABETIC ANGIOPATHY; ENDOCRINOLOGY; HISTORY; MEDICAL SOCIETY; ORGANIZATION AND MANAGEMENT; PROCEDURES; STANDARD; UNITED STATES;

CARDIOVASCULAR DISEASES; DIABETES MELLITUS; DIABETIC ANGIOPATHIES; ENDOCRINOLOGY; HEART DISEASE RISK FACTORS; HISTORY, 21ST CENTURY; HUMANS; REFERENCE STANDARDS; SOCIETIES, MEDICAL; STANDARD OF CARE; UNITED STATES;

EID: 85077048167     PISSN: 01495992     EISSN: 19355548     Source Type: Journal    
DOI: 10.2337/dc20-S010     Document Type: Article

References (188)

1. American Diabetes Association. Economic costs of diabetes in the U.S. in 2017. Diabetes Care 2018;41:917–928
2. Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in U.S.diabetescare,1999-2010.N EnglJMed2013; 368:1613–1624
3. Buse JB, Ginsberg HN, Bakris GL, et al.; American Heart Association; American Diabetes Association. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 2007;30: 162–172
4. Gaede P, Lund-Andersen H, Parving H-H, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008;358:580–591
5. Cavender MA, Steg PG, Smith SC Jr, et al.; REACH Registry Investigators. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the Reduction of Atherothrombosis for Continued Health (REACH) registry. Circulation 2015;132:923–931
6. McAllister DA, Read SH, Kerssens J, et al. Incidence of hospitalization for heart failure and case-fatality among 3.25 million people with and without diabetes mellitus. Circulation 2018;138: 2774–2786
7. Lam CSP, Voors AA, de Boer RA, Solomon SD, van Veldhuisen DJ. Heart failure with preserved ejection fraction: from mechanisms to therapies. Eur Heart J 2018;39:2780–2792
8. Zinman B, Wanner C, Lachin JM, et al.; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117–2128
9. Neal B, Perkovic V, Mahaffey KW, et al.; CANVAS Program Collaborative Group. Canagli-flozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644–657
10. Fitchett D, Butler J, van de Borne P, et al.; EMPA-REG OUTCOMEÒ trial investigators. Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOMEÒ trial. Eur Heart J 2018;39:363-370
11. Blood Pressure Lowering Treatment Trialists’ Collaboration. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet 2014;384:591–598
12. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/ APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;73:3168–3209
13. Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations. JAMA 2014;311:1406–1415
14. DeFilippisAP, Young R, McEvoyJW, et al. Risk score overestimation: the impact of individual cardiovascular risk factors and preventive therapies on the performance of the American Heart Association-American College of Cardiology-Ath-erosclerotic Cardiovascular Disease risk score in a modern multi-ethnic cohort. Eur Heart J 2017;38: 598–608
15. Bohula EA, Morrow DA, Giugliano RP, et al. Atherothrombotic risk stratification and ezeti-mibe for secondary prevention. J Am Coll Cardiol 2017;69:911–921
16. Bohula EA, Bonaca MP, Braunwald E, et al. Atherothrombotic risk stratification and the efficacy and safety of vorapaxar in patients with stable ischemic heart disease and previous myocardial infarction. Circulation 2016;134: 304–313
17. de Boer IH, Bangalore S, Benetos A, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care 2017;40:1273–1284
18. Bobrie G, Genès N, Vaur L, et al. Is “isolated home” hypertension as opposed to “isolated office” hypertension a sign of greater cardiovascular risk? Arch Intern Med 2001;161:2205–2211
19. Sega R, Facchetti R, Bombelli M, et al. Prognostic value of ambulatory and home blood pressures comparedwithoffice blood pressurein the general population: follow-up results from the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Circulation 2005;111: 1777–1783
20. Omboni S, Gazzola T, Carabelli G, Parati G. Clinical usefulness and cost effectiveness of home blood pressuretelemonitoring: meta-analysis of randomized controlled studies. J Hypertens 2013;31:455–467; discussion 467–468
21. Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 2015;313:603–615
22. Arguedas JA, Leiva V, Wright JM. Blood pressure targets for hypertension in people with diabetes mellitus. Cochrane Database Syst Rev 2013;10:CD008277
23. Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016;387:957–967
24. Brunström M, Carlberg B. Effect of antihy-pertensive treatment at different blood pressure levels in patients with diabetes mellitus: system-aticreviewandmeta-analyses. BMJ2016;352:i717
25. Bangalore S, Kumar S, Lobach I, Messerli FH. Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and Bayesian ran-dom-effects meta-analyses of randomized trials. Circulation 2011;123:2799–2810
26. Thomopoulos C, Parati G, Zanchetti A. Effects of blood-pressure-lowering treatment on outcome incidence in hypertension: 10-should blood pressure management differ in hypertensive patients with and without diabetes mellitus? Overview and meta-analyses of randomized trials. J Hypertens 2017;35:922–944
27. Xie X, Atkins E, Lv J, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet 2016;387:435–443
28. Cushman WC, Evans GW, Byington RP, et al.; ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575–1585
29. Patel A, MacMahon S, Chalmers J, et al.; ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007;370:829–840
30. Bakris GL. The implications of blood pressure measurement methods on treatment targets for blood pressure. Circulation 2016;134:904–905
31. Margolis KL, O’Connor PJ, Morgan TM, et al. Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial. Diabetes Care 2014; 37:1721–1728
32. Buckley LF, Dixon DL, Wohlford GF 4th, Wijesinghe DS, Baker WL, Van Tassell BW. Intensive versus standard blood pressure control in SPRINT-eligible participants of ACCORD-BP. Diabetes Care 2017;40:1733–1738
33. Brouwer TF, Vehmeijer JT, Kalkman DN, et al. Intensive blood pressure lowering in patients with and patients without type 2 diabetes: a pooled analysis from two randomized trials. Diabetes Care 2018;41:1142–1148
34. Lamprea-Montealegre JA, de Boer IH. Reevaluating the evidence for blood pressure targetsintype2diabetes.DiabetesCare2018;41: 1132–1133
35. de Boer IH, Bakris G, Cannon CP. Individu-alizing blood pressure targets for people with diabetes and hypertension: comparing the ADA and the ACC/AHA recommendations. JAMA 2018;319:1319–1320
36. Basu S, Sussman JB, Rigdon J, Steimle L, Denton BT, Hayward RA. Benefit and harm of intensive blood pressure treatment: derivation and validation of risk models using data from the SPRINT and ACCORD trials. PLoS Med 2017;14:e1002410
37. Phillips RA, Xu J, Peterson LE, Arnold RM, Diamond JA, Schussheim AE. Impact of cardiovascular risk on the relative benefit and harm of intensive treatment of hypertension. J Am Coll Cardiol 2018;71:1601–1610
38. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:e127–e248
39. Wright JT Jr, Williamson JD, Whelton PK, et al.; SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:2103–2116
40. Beddhu S, Greene T, Boucher R, et al. Intensive systolic blood pressure control and incident chronic kidney disease in people with and without diabetes mellitus: secondary analyses of two randomised controlled trials. Lancet Diabetes Endocrinol 2018;6:555–563
41. Sink KM, Evans GW, Shorr RI, et al. Syncope, hypotension, and falls in the treatment of hy-pertension: results from the randomized clinical systolic blood pressure intervention trial. J Am Geriatr Soc 2018;66:679–686
42. Abalos E, Duley L, Steyn DW. Antihyperten-sive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2014;2:CD002252
43. Magee LA, von Dadelszen P, Rey E, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med 2015;372:407–417
44. Brown MA, Magee LA, Kenny LC, et al.; International Society for the Study of Hypertension in Pregnancy(ISSHP).Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension 2018; 72:24–43
45. American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013;122:1122–1131
46. Al-Balas M, Bozzo P, Einarson A. Use of diuretics during pregnancy. Can Fam Physician 2009;55:44–45
47. Irgens HU, Reisaeter L, Irgens LM, Lie RT. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ 2001;323:1213–1217
48. Sacks FM, Svetkey LP, Vollmer WM, et al.; 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
49. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline forthe management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311: 507–520
50. Bakris GL, Weir MR; Study of Hypertension and the Efficacy of Lotrel in Diabetes (SHIELD) Investigators. Achieving goal blood pressure in patients with type 2 diabetes: conventional versus fixed-dose combination approaches. J Clin Hypertens (Greenwich) 2003;5:202–209
51. FeldmanRD, ZouGY, Vander voort MK, Wong CJ, Nelson SAE, Feagan BG. A simplified approach to the treatment of uncomplicated hypertension: a cluster randomized, controlled trial. Hypertension 2009;53:646–653
52. Webster R, Salam A, de Silva HA, Selak V, Stepien S, Rajapakse S, et al. Fixed low-dose triple combination antihypertensive medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka: a randomized clinical trial. JAMA 2018;320:566–579
53. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 2007;120:713–719
54. Catalá-López F, Macías Saint-Gerons D, González-Bermejo D, et al. Cardiovascular and renal outcomes of renin-angiotensin system blockade in adult patients with diabetes mellitus: a systematic review withnetwork meta-analyses. PLoS Med 2016;13:e1001971
55. Palmer SC, Mavridis D, Navarese E, et al. Comparative efficacy and safety of blood pres-sure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet 2015;385:2047–2056
56. Barzilay JI, Davis BR, Bettencourt J, et al.; ALLHAT Collaborative Research Group. Cardiovascular outcomes using doxazosin vs. chlortha-lidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study. J Clin Hypertens (Greenwich) 2004;6:116–125
57. Weber MA, Bakris GL, Jamerson K, et al.; ACCOMPLISH Investigators. Cardiovascular events during differing hypertension therapies in patients with diabetes. J Am Coll Cardiol 2010;56: 77–85
58. Bangalore S, Fakheri R, Toklu B, Messerli FH. Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials. BMJ 2016;352:i438
59. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet 2004;364:1684–1689
60. Yusuf S, Teo KK, Pogue J, et al.; ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547–1559
61. Fried LF, Emanuele N, Zhang JH, et al.; VA NEPHRON-D Investigators. Combined angio-tensin inhibition for the treatment of diabetic nephropathy. N Engl J Med 2013;369:1892-1903
62. Makani H, Bangalore S, Desouza KA, Shah A, Messerli FH. Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials. BMJ 2013;346:f360
63. Zhao P, Xu P, Wan C, Wang Z. Evening versus morning dosing regimen drug therapy for hypertension. Cochrane Database Syst Rev 2011; 10:CD004184
64. Hermida RC, Ayala DE, Mojón A, Fernández JR. Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care 2011;34:1270–1276
65. Nilsson E, Gasparini A, Ärnlöv J, et al. Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system. Int J Cardiol 2017;245:277–284
66. Bandak G, Sang Y, Gasparini A, et al. Hyper-kalemia after initiating renin-angiotensin system blockade: the Stockholm Creatinine Measurements (SCREAM) project. J Am Heart Assoc 2017; 6:e005428
67. Hughes-Austin JM, Rifkin DE, Beben T, et al. The relation of serum potassium concentration with cardiovascular events and mortality in community-living individuals. Clin J Am Soc Nephrol 2017;12:245–252
68. James MT, Grams ME, Woodward M, et al.; CKD Prognosis Consortium. A meta-analysis of the association of estimated GFR, albuminuria, diabetes mellitus, and hypertension with acute kidney injury. Am J Kidney Dis 2015;66: 602–612
69. Iliescu R, Lohmeier TE, Tudorancea I, LaffinL, Bakris GL. Renal denervation for the treatment of resistant hypertension: review and clinical perspective. Am J Physiol Renal Physiol 2015;309: F583–F594
70. Bakris GL, Agarwal R, Chan JC, et al.; Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy (ARTS-DN) Study Group. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA 2015;314:884–894
71. Williams B, MacDonald TM, Morant S, et al.; British Hypertension Society’s PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015;386:2059–2068
72. Filippatos G, Anker SD, Böhm M, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J 2016;37: 2105–2114
73. Bomback AS, Klemmer PJ. Mineralocorticoid receptor blockade in chronic kidney disease. Blood Purif 2012;33:119–124
74. Jensen MD, Ryan DH, Apovian CM, et al.; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 2014;63(25 Pt B): 2985–3023
75. Estruch R, Ros E, Salas-Salvadó J, et al.; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34
76. 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 2013;129:S76–S99
77. Chasman DI, Posada D, Subrahmanyan L, Cook NR, Stanton VP Jr, Ridker PM. Pharmaco-genetic study of statin therapy and cholesterol reduction. JAMA 2004;291:2821–2827
78. Meek C, Wierzbicki AS, Jewkes C, et al. Daily and intermittent rosuvastatin 5 mg therapy in statin intolerant patients: an observational study. Curr Med Res Opin 2012;28:371-378
79. Mihaylova B, Emberson J, Blackwell L, et al.; Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380:581–590
80. Baigent C, Keech A, Kearney PM, et al.; Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lower-ing treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-1278
81. Pyŏrälä K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 1997;20:614–620
82. Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003;361:2005–2016
83. Goldberg RB, Mellies MJ, Sacks FM, et al.; The Care Investigators. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the Cholesterol and Recurrent Events (CARE) trial. Circulation 1998;98: 2513–2519
84. Shepherd J, Barter P, Carmena R, et al. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care 2006;29:1220–1226
85. Sever PS, Poulter NR, Dahlöf B, et al. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial-lipid-lowering arm (ASCOT-LLA). Diabetes Care 2005;28:1151–1157
86. Knopp RH, d’Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN). Diabetes Care 2006;29: 1478–1485
87. Colhoun HM, Betteridge DJ, Durrington PN, etal.; CARDSinvestigators. Primaryprevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685-696
88. Kearney PM, Blackwell L, Collins R, et al.; Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008; 371:117–125
89. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013; 1:CD004816
90. Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study [published correction appears in BMJ 2013;347:f4356]. BMJ 2013;346:f2610
91. Baigent C, Blackwell L, Emberson J, et al.; Cholesterol Treatment Trialists’ (CTT) Collaboration. 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;376:1670–1681
92. Cannon CP, Blazing MA, Giugliano RP, et al.; IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015;372:2387–2397
93. De Ferranti SD, de Boer IH, Fonseca V, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation 2014;130: 1110–1130
94. Cannon CP, Braunwald E, McCabe CH, et al.; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350: 1495–1504
95. Sabatine MS, Giugliano RP, Keech AC, et al.; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376:1713–1722
96. Giugliano RP, Cannon CP, Blazing MA, et al.; IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus: results from IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Tri-al). Circulation 2018;137:1571–1582
97. Das SR, Everett BM, Birtcher KK, et al. 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2018;72:3200–3223
98. Moriarty PM, Jacobson TA, Bruckert E, et al. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol 2014;8: 554–561
99. Zhang X-L, Zhu Q-Q, Zhu L, et al. Safety and efficacy of anti-PCSK9 antibodies: a meta-anal-ysis of 25 randomized, controlled trials. BMC Med 2015;13:123
100. Sabatine MS, Leiter LA, Wiviott SD, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol 2017;5:941–950
101. Berglund L, Brunzell JD, Goldberg AC, et al.; Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97:2969–2989
102. Bhatt DL, Steg PG, Miller M, et al.; REDUC-E-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11–22
103. Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutic target: a systematic review. JAMA 2007;298:786–798
104. Keech A, Simes RJ, Barter P, et al.; FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005;366:1849–1861
105. Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate 1 statin versus gemfibrozil 1 any statin. Am J Cardiol 2005;95: 120–122
106. Ginsberg HN, Elam MB, Lovato LC, et al.; ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010;362:1563–1574
107. Kowa Research Institute, Inc. Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes (PROM-INENT) In: ClinicalTrials.gov [Internet]. Bethesda, MD, National Library of Medicine. NLM Identifier: NCT03071692. Accessed 8 October 2018. Available from https://clinicaltrials.gov/ct2/show/NCT03071692
108. Boden WE, Probstfield JL, Anderson T, et al.; AIM-HIGH Investigators. Niacin in patients withlow HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011;365:2255–2267
109. Landray MJ, Haynes R, Hopewell JC, et al.; HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014;371: 203–212
110. Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care 2009;32:1924–1929
111. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375:735–742
112. RidkerPM, PradhanA,MacFadyenJG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 2012;380: 565–571
113. Mach F, Ray KK, Wiklund O, et al.; European Atherosclerosis Society Consensus Panel. Adverse effects of statin therapy: perception vs. the evidence -focus on glucose homeostasis, cognitive, renal and hepatic function, haemor-rhagic stroke and cataract. Eur Heart J 2018;39: 2526–2539
114. 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
115. Shepherd J, Blauw GJ, Murphy MB, et al.; PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623–1630
116. Trompet S, van Vliet P, de Craen AJM, et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol 2010;257: 85–90
117. Yusuf S, Bosch J, Dagenais G, et al.; HOPE-3 Investigators. Cholesterol lowering in interme-diate-risk persons without cardiovascular disease. N Engl J Med 2016;374:2021–2031
118. Giugliano RP, Mach F, Zavitz K, et al.; EBBINGHAUS Investigators. Cognitive function in a randomizedtrial ofevolocumab.NEngl J Med 2017;377:633–643
119. Richardson K, Schoen M, French B, et al. Statins and cognitive function: a systematic review. Ann Intern Med 2013;159:688–697
120. Baigent C, Blackwell L, Collins R, et al.; Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849–1860
121. Perk J, De Backer G, Gohlke H, et al.; European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). 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 (consti-tuted by representatives of nine societies and by invited experts). Eur Heart J 2012;33:1635-1701
122. Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antiox-idants in patients with diabetes and asymptom-atic peripheral arterial disease. BMJ 2008;337: a1840
123. Zhang C, Sun A, Zhang P, et al. Aspirin for primary prevention of cardiovascular events in patients with diabetes: a meta-analysis. Diabetes Res Clin Pract 2010;87:211–218
124. De Berardis G, Sacco M,Strippoli GFM,et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. BMJ 2009;339: b4531
125. ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018;379:1529-1539
126. Gaziano JM, Brotons C, Coppolecchia R, et al.; ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet 2018;392:1036–1046
127. McNeilJJ, Wolfe R,WoodsRL, etal.; ASPREE Investigator Group. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018;379:1509–1518
128. Pignone M, Earnshaw S, Tice JA, Pletcher MJ. Aspirin, statins, or both drugs for the primary prevention of coronary heart disease events in men:acost-utilityanalysis. Ann Intern Med2006; 144:326–336
129. Huxley RR, Peters SAE, Mishra GD, Woodward M. Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2015;3:198–206
130. Peters SAE, Huxley RR, Woodward M. Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events. Diabetologia 2014; 57:1542–1551
131. Kalyani RR, Lazo M, Ouyang P, et al. Sex differences in diabetes and risk of incident coronary artery disease in healthy young and middle-aged adults. Diabetes Care 2014;37:830–838
132. Peters SAE, Huxley RR, Woodward M. Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775,385 individuals and 12,539 strokes. Lancet 2014;383: 1973–1980
133. Miedema MD, Duprez DA, Misialek JR, et al. Use of coronary artery calcium testing to guide aspirin utilization for primary prevention: esti-mates from the multi-ethnic study of athero-sclerosis. Circ Cardiovasc Qual Outcomes 2014;7: 453–460
134. Dimitriu-Leen AC, Scholte AJHA, van Rosendael AR, et al. Value of coronary computed tomography angiography in tailoring aspirin therapy for primary prevention of atherosclerotic events in patients at high risk with diabetes mellitus. Am J Cardiol 2016;117: 887–893
135. Mora S, Ames JM, Manson JE. Low-dose aspirin in the primary prevention of cardiovascular disease: shared decision making in clinical practice. JAMA 2016;316:709–710
136. Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA 2007;297:2018–2024
137. Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007;357:2482-2494
138. Larsen SB, Grove EL, Neergaard-Petersen S, Würtz M, Hvas A-M, Kristensen SD. Determinants of reduced antiplatelet effect of aspirin in patients with stable coronary artery disease. PLoS One 2015;10:e0126767
139. Zaccardi F, Rizzi A, Petrucci G, et al. In vivo platelet activation and aspirin responsiveness in type 1 diabetes. Diabetes 2016;65:503–509
140. Bethel MA, Harrison P, Sourij H, et al. Randomized controlled trial comparing impact on platelet reactivity of twice-daily with oncedaily aspirin in people with type 2 diabetes. Diabet Med 2016;33:224–230
141. Rothwell PM, Cook NR, Gaziano JM, et al. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. Lancet 2018;392:387–399
142. Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Guidelines [published correction appears in Chest 2012;141:1129]. Chest 2012; 141(Suppl.):e637S–e668S
143. Bhatt DL, Bonaca MP, Bansilal S, et al. Reduction in ischemic events with ticagrelor in diabetic patients with prior myocardial infarction in PEGASUS-TIMI 54. J Am Coll Cardiol 2016;67:2732–2740
144. Bax JJ, Young LH, Frye RL, Bonow RO, Steinberg HO, Barrett EJ; ADA. Screening for coronary artery disease in patients with diabetes. Diabetes Care 2007;30:2729–2736
145. Boden WE, O’Rourke RA, Teo KK, et al.; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503–1516
146. BARI 2D Study Group, Frye RL, August P, et al. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009;360:2503–2015
147. Wackers FJT, Chyun DA, Young LH, et al.; Detection of Ischemia in Asymptomatic Diabetics (DIAD) Investigators. Resolution of asymptomatic myocardial ischemia in patients with type 2 diabetes in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Diabetes Care 2007;30:2892–2898
148. Elkeles RS, Godsland IF, Feher MD, et al.; PREDICT Study Group. Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study. Eur Heart J 2008;29: 2244–2251
149. Raggi P, Shaw LJ, Berman DS, Callister TQ. Prognostic value of coronary artery calcium screening in subjects with and without diabetes. J Am Coll Cardiol 2004;43:1663–1669
150. Anand DV, Lim E, Hopkins D, et al. Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy. Eur Heart J 2006;27:713–721
151. Young LH, Wackers FJT, Chyun DA, et al.; DIAD Investigators. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA 2009;301:1547–1555
152. Wackers FJT, Young LH, Inzucchi SE, et al.; Detection of Ischemia in Asymptomatic Diabetics Investigators. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care 2004;27:1954–1961
153. Scognamiglio R, Negut C, Ramondo A, Tiengo A, Avogaro A. Detection of coronary artery disease in asymptomatic patients with type 2 diabetes mellitus. J Am Coll Cardiol 2006; 47:65–71
154. Hadamitzky M, Hein F, Meyer T, et al. Prognostic value of coronary computed tomo-graphic angiography in diabetic patients without known coronary artery disease. Diabetes Care 2010;33:1358–1363
155. Choi E-K, ChunEJ, Choi S-I,etal. Assessment of subclinical coronary atherosclerosis in asymptomatic patients with type 2 diabetes mellitus with single photon emission computed tomog-raphy and coronary computed tomography an-giography. Am J Cardiol 2009;104:890–896
156. Malik S, Zhao Y, Budoff M, et al. Coronary artery calcium score for long-term risk classification in individuals with type 2 diabetes and metabolic syndrome from the multi-ethnic study of atherosclerosis. JAMA Cardiol 2017;2:1332-1340
157. Wing RR, Bolin P, Brancati FL, et al.; Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 di-abetes. N Engl J Med 2013;369:145–154
158. Braunwald E, Domanski MJ, Fowler SE, et al.; PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 2004;351:2058-2068
159. Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators, Yusuf S, Teo K, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet 2008;372:1174–1183
160. Kezerashvili A, Marzo K, De Leon J. Beta blocker use after acute myocardial infarction in the patient with normal systolic function: when is it “ok” to discontinue? Curr Cardiol Rev 2012;8: 77–84
161. U.S. Food and Drug Administration. Guidance for industry. Diabetes mellitusdevaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. Silver Spring, MD, 2008. Accessed 3 November 2017. Available from http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071627.pdf
162. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380:2295-2306
163. Neal B, Perkovic V, Matthews DR, et al.; CANVAS-R Trial Collaborative Group. Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R): a randomized, placebocontrolled trial. Diabetes Obes Metab 2017;19: 387–393
164. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347–357
165. Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375: 311–322
166. Marso SP, Bain SC, Consoli A, et al.; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375: 1834–1844
167. Husain M, Birkenfeld AL,Donsmark M,et al. Oral semaglutideand cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2019; 381:841–851
168. Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 2018;392:1519–1529
169. Gerstein HC, Colhoun HM, Dagenais GR, et al.; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (RE-WIND): a double-blind, randomised placebo-controlled trial. Lancet 2019;394:121–130
170. Pfeffer MA, Claggett B, Diaz R, et al.; ELIXA Investigators. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 2015;373:2247–2257
171. Holman RR, Bethel MA, Mentz RJ, et al.; EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017;377:1228–1239
172. Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotrans-porter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation 2019;139: 2022–2031
173. Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019;393:31–39
174. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol 1974;34:29–34
175. Dormandy JA, Charbonnel B, Eckland DJA, et al.; PROactive Investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVas-cular Events): a randomised controlled trial. Lancet 2005;366:1279–1289
176. Singh S, Loke YK, FurbergCD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 2007;298:1189–1195
177. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patientswithtype2diabetesmellitus:ameta-analysis of randomized trials. JAMA 2007;298:1180–1188
178. Inzucchi SE, Masoudi FA, McGuire DK. Metformin in heart failure. Diabetes Care 2007;30:e129–e129
179. Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care 2005;28:2345–2351
180. U.S. Food and Drug Administration. FDA drug safety communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function, 2016. Accessed 14 October 2016. Available from http://www.fda.gov/Drugs/DrugSafety/ucm493244.htm
181. Scirica BM, Bhatt DL, Braunwald E, et al.; SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317–1326
182. Zannad F, Cannon CP, Cushman WC, et al.; EXAMINE Investigators. Heart failure and mortality outcomes in patients with type 2 diabetes taking aloglipt in versus place boin EXAMINE: amulti centre, randomised, double-blind trial. Lancet 2015;385: 2067–2076
183. Green JB, Bethel MA, Armstrong PW, et al.; TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;373:232–242
184. Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA 2019;321:69–79
185. Hansson L, Zanchetti A, Carruthers SG, et al.; HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998;351:1755-1762
186. White WB, Cannon CP, Heller SR, et al.; EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369:1327–1335
187. Rosenstock J, Perkovic V, Alexander JH, et al. Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin (CARMELINA): a randomized, double-blind, placebocontrolled clinical trial in patients with type 2 diabetes and high cardio-renal risk. Cardiovasc Diabetol 2018;17:39
188. Cefalu WT, Kaul S, Gerstein HC, et al. Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? Reflections from a Diabetes Care Editors’ Expert Forum. Diabetes Care 2018;41:14–31