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Diabetologie und Stoffwechsel 2018; 13(05): 403-422
DOI: 10.1055/s-0043-124740
DOI: 10.1055/s-0043-124740
CME-Fortbildung
Medikamentöse Therapie von Fettstoffwechselstörungen bei Patienten mit Typ-2-Diabetes
Koronare Risikoreduktion durch intensive Senkung von LDL-CholesterinFurther Information
Publication History
Publication Date:
11 October 2018 (online)
Diabetes ist meist mit einem deutlich erhöhten kardiovaskulären Risiko assoziiert. Atherogene Lipoproteine, wie z. B. LDL (Low Density Lipoprotein), sind ein kausaler Risikofaktor, und ihre Senkung mittels einer Erhöhung der hepatischen LDL-Rezeptoren durch Statine, Ezetimib und/oder PCSK-9-Antikörper ist mit einer Reduktion kardiovaskulärer Komplikationen assoziiert.
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Literatur
- 1 Schramm TK, Gislason GH, Kober L. et al. Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3.3 million people. Circulation 2018; 117: 1945-1954
- 2 Rawshani A, Sattar N, Franzen S. et al. Excess mortaility and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet 2018; 392: 477-486
- 3 Rawshani A, Rawshani A, Franzen S. et al. Risk factors, mortality, and cardiovasular outcomes in patients with type 2 diabetes. N Engl J Med 2018; 379: 633-644
- 4 Gaede P, Oellgaard J, Carstensen B. et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years of follow-up on the Steno-2 randomised trial. Diabetologia 2016; 59: 2298-2307
- 5 Brownrigg JR, Hughes CO, Burleigh D. et al. Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study. Lancet Diabetes Endocrinol 2016; 4: 588-597
- 6 Merkel M, Müller-Wieland D, von Eckerdstein A. Fettstoffwechsel. In: Blum HE, Müller-Wieland D. Hrsg Klinische Pathophysiologie. Stuttgart, New York: Thieme Verlag; 2018: 200-231
- 7 Taskinen MR, Boren J. New insights into the pathophysiology of dyslipidemia in type 2 diabetes. Atherosclerosis 2015; 239: 483-495
- 8 Hagihkia A, Landmesser U. HDL Effects of apolipoprotein a-I/High-Density Lipoprotein cholesterol on atherosclerotic vascular disease: Critical impact of atherosclerosis disease stage and disease milieu?. JACC Basic Transl Sci 2018; 3: 210-212
- 9 Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell 2015; 161: 161-172
- 10 Catapano AL, Graham I, De Backer G. et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016; 37: 2999-3058 ; Epub ahead August 27, doi:10.1093/eurheartj/ehw272. 11
- 11 Shaikh M, Wootton R, Nordestgaard BG. et al. Quantitative studies of transfer in vivo of low density, Sf 12-60, and Sf 60-400 lipoproteins between plasma and arterial intima in humans. Arterioscler Thromb Vasc Biol 1991; 11: 569-577
- 12 Nordestgaard BG, Wootton R, Lewis B. Selective retention of VLDL, IDL, and LDL in the arterial intima of genetically hyperlipidemic rabbits in vivo. Arterioscler Thromb Vasc Biol 1995; 15: 534-542
- 13 Varbo A, Benn M, Tybjærg-Hansen A. et al. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013; 61: 427-436
- 14 Varbo A, Nordestgaard BG. Remnant cholesterol and triglyceride-rich lipoproteins in atherosclerosis progression and cardiovascular disease. Arterioscler Thromb Vasc Biol 2016; 36: 2133
- 15 Joshi PH, Khokhar AA, Massaro JM. et al. Remnant lipoprotein cholesterol and incident coronary heart disease: the jackson heart and framingham offspring cohort studies. J Am Heart Assoc 2016; 5: e002765
- 16 Boekholdt SM, Arsenault BJ, Mora S. et al. Association of LDL cholesterol, non–HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. J Am Med Assoc 2012; 307: 1302-1309
- 17 Robinson JG, Wang S, Smith BJ. et al. 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
- 18 Cui Y, Blumenthal RS, Flaws JA. et al. Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med 2001; 161: 1413-1419
- 19 Liu J, Sempos C, Donahue RP. et al. Joint distribution of non-HDL and LDL cholesterol and coronary heart disease risk prediction among individuals with and without diabetes. Diabetes Care 2005; 28: 1916-1921
- 20 Vallejo-Vaz AJ, Fayyad R, Boekholdt SM. et al. Triglycerid-rich lipoprotein cholesterol and risk of cardiovascular events among patients receiving statin therapy in the Treating to New Targets (TNT) trial. Circulation 2018;
- 21 Jacobsen TA, Ito MK, Maki KC. et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1-ececutive summary. J Clin Lipidol 2014; 8: 473-488
- 22 Okopien B, Buldak L, Boldys A. Fibrates in the management of atherogenic dyslipidemia. Expert Rev Cardiovasc Ther 2017; 15: 913-921
- 23 Rubins HB, Robins SJ, Collins D. et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med 2002; 162: 2597-2604
- 24 Rubins HB, Robins SJ, Collins D. et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs high-density lipoprotein cholesterol intervention trial study group. N Engl J Med 1999; 341: 410-418
- 25 Frick MH, Elo O, Haapa K. et al. 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
- 26 Arbel Y, Klempfner R, Erez A. et al. Bezafibrate for the treatment of diyslipidemia in patients with coronary artery disease: 20-ywear mortaility follow-up of the BIP randomized control trial. Cardiovasc Diabetol 2016;
- 27 Scott R, O´Brien R, Fulcher G. et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9795 individuals with type 2 diabetes and various components of the metabolic syndrome: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care 2009; 32: 493-498
- 28 Ginsberg HN, Elam MB. ACCORD Study Group. et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010; 362: 1563-1574
- 29 Ridker PM. LDL cholesterol: controversies and future therapeutic directions. Lancet 2014; 384: 607-617
- 30 Olsson AG, Angelin B, Assmann G. et al. Can LDL cholesterol be too low? Possible risks of extreme low levels. J Intern Med 2017; 281: 534-553
- 31 Mach F, Ray KK, Wiklund O. et al. Adverse effects of statin therapy: perception vs. the evidence – focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. Eur Heart J 2018; 39: 2526-2539
- 32 Robinson JG. Statins and diabetes risk: how real is it and what are the mechanisms?. Curr Opin Lipidol 2015; 26: 228-235
- 33 Muscogiuri G, Samo G, Gastaldelli A. et al. The good and bad effects of statins on insulin sensitivity and insulin secretion. Endocr Res 2014; 39: 137-143
- 34 Betteridge DJ, Carmena R. The diabetogenic action of statins – mechanisms and clinical implications. Nat Rev Endocrinol 2016; 12: 99-110
- 35 Kearney PM, Blackwell L, Collins R. Cholesterol Treatment Trialists (CTT) Collaborators. et al. Efficacy of cholesterol-lowering therapy in 18686 people with diabetes in 14 randomized trials of statins: a meta-analysis. Lancet 2008; 371: 117-125
- 36 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: 2005-2026
- 37 Colhoun HM, Betteridge DJ, Durrington PN. on behalf of the CARDS investigators. et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabets in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685-696
- 38 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
- 39 Cannon CP, Braunwald E, McCabe CH. et al. for the 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
- 40 Phan BA, Dayspring TD, Toth PP. Ezetimibe therapy: mechanisms of action and clinical update. Vasc Health Risk Manag 2012; 8: 415-427
- 41 Friedman HS, Rajagopalan S, Barnes JP. et al. Combination therapy with ezetimibe/simvastatin versus statin monotherapy for low density lipoprotein cholesterol reduction and goal attainment in a real world setting. Clin Ther 2011; 33: 212-224
- 42 Cannon CP, Blazing MA, Giugliano RP. et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372: 2387-2397
- 43 Giugliano RP, Cannon CP, Blazing MA. et al. 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 Trial). Circulation 2018; 137: 1571-1582
- 44 Nissen SE, Tuzcu EM, Schoenhagen P. for the REVERSAL Investigators. et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis. A randomized controlled trial. JAMA 2004; 291: 1071-1080
- 45 Nissen SE, Nicholls SJ, Sipahi I. et al. for the ASTEROID Investigators: Effect of very high-intensity statin therapy on regression of coronary atherosclerosis. The ASTEROID Trial. JAMA 2006; 295: E1-E10
- 46 Nicholls SJ, Puri R, Anderson T. et al. Effect of evolocumab on progression of coronary disease in statin-treated patients. The GLAGOV randomized clinical trial. JAMA 2016; 316: 2373-2384
- 47 Abifadel M, Varret M, Rabes JP. et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003; 34: 154-156
- 48 Cohen JC, Boerwinkle E, Mosley Jr TH. et al. Sequence variations in PCSK9, low LDL, and protection agaimst coronary heart disease. N Engl J Med 2006; 354: 1264-1272
- 49 Robinson JG, Farnier M, Krempf M. et al. Efiicacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372: 1489-1499
- 50 Sabatine MS, Giugliano RP, Wiviott SD. et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372: 1500-1509
- 51 Karatasakis A, Daenk BA, Karacsonyi J. et al. Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia: A meta-analysis of 35 randomized controlled trials. J Am Heart Assoc 2017; 6: ee006910 . DOI: 10.1161/JAHA.117.006910
- 52 Watts GF, Chan DC, Somarantne R. et al. Controlled study of the effect of proprotein convertase subtilisin-kexin type 9 inhibition with evolocumab on lipoprotein (a) particle kinetics. Eur Heart J 2018; 39: 2577-2585
- 53 Handelsman Y, Lepor NE. PCSK9 inhibitors in lipid management of patients with diabetes mellitus and high cardiovascular risk: a review. J Am Heart Assoc 2018;
- 54 Henry RR, Müller-Wieland D, Taub PR. et al. Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials. Diabetes Obes Metab 2018; 20: 1632-1641
- 55 Ginsberg HN, Farnier M, Robinson JG. et al. Efficacy and safety of alirocumab in individuals with diabetes emllitus: pooled analyses from five placebo-controlled phase 3 studies. Diabetes Ther 2018; 9: 1317-1334
- 56 Blom DJ, Koren MJ, Roth E. et al. Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome. Diabetes Obes Metab 2017; 19: 98-107
- 57 Cao YX, Liu HH, Dong QT. et al. Effect of proprotein convertase subtilisin7kexin type 9 (PCSK9) monoclonal antibodies on new-onset diabetes mellitus and glucose metabolism: A systematic review and meta-analysis. Diabetes Obes Metab 2018; 20: 1391-1398
- 58 de Carvalho LSF, Campos AM, Sposito AC. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incident type 2 diabetes: a systematic review and meta-analysis with over 96000 patient-years. Diabetes Care 2018; 41: 364-336
- 59 Sattar N, Toth PP, Blom DJ. et al. Effect of proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab on glycemia, body weight, and new-onset diabetes mellitus. Am J Cardiol 2017; 120: 1521-1527
- 60 Leiter LA, Cariou B, Müller-Wieland D. et al. Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM-INSULIN randomized trial. Diabetes Obes Metab 2017; 19: 1781-1792
- 61 Müller-Wieland D, Leiter LA, Cariou B. et al. Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidemia at high cardiovascular risk. Cardiovasc Diabetol 2017; 16: 70 . doi: 10.1186/s12933-0
- 62 Ray KK, Leiter LA, Müller-Wieland D. et al. Alirocumab vs usual lipid-lowering care as add-on to statin therapy in indiciduals with type 2 diabetes and mixed dyslipidemia: The ODYSSEY DM-DYSLIDEMIA randomized trial. Diabetes Obes Metab 2018; 20: 1479-1489
- 63 Reyes-Soffer G, Pavlyha M, Ngai C. et al. Effects of PCSK9 inhibition with alirocumab on lipoprotein metabolism in healthy humans. Circulation 2017; 135: 352-362
- 64 Sabatine MS, Giugliano RP, Keech AC. et al. Evolocumab and clinical outomes in patinets with cardiovascular disease. N Engl J Med 2017; 376: 1713-1722
- 65 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 glycemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol 2017; 5: 941-950
- 66 Schwartz GG, Szarek M, Bhatt DL. et al. The ODYSSEY OUTCOMES Trial: Topline results Alirocumab in patients after acute coronary syndrome. American College of Cardiology – 67th Scientific Sessions. March 10, 2018
- 67 Ray KK, Colhoun H, Szarek M. et al. Alirocumab and cardiovascular outcomes in patients with acute coronary syndrome (ACS) and diabetes – prespecified analyses of ODYSSEY OUTCOMES. ADA; 2018: 6-LB 9
- 68 Giugliano RP, Pedersen TR, Park JG. et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified analysis of the FOURIER trial. Lancet 2017; 390: 1962-1971
- 69 Landmesser U, Chapman MJ, Stock JK. et al. 2017 update of ESC/EAS Task Force on practical clinical guidance for proprotein convertase subtilisin/kexin 9 inhibition in patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia. Eur Heart J 2018; 39: 1131-1143
- 70 Landmesser U, Chapman MJ, Stock JK. et al. New perspectives for PCSK9 inhibition?. Eur Heart J 2018; 39: 2600-2601
- 71 Wiegman A, Gidding SS, Watts GF. et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015; 36: 2425-2437
- 72 Laufs U, Scharnagl H, Halle M. et al. Behandlungsoptionen bei Statin-assoziierten Muskelbeschwerden. Dtsch Arztebl Int 2015; 112: 748-755