Dtsch Med Wochenschr 2016; 141(12): 857-862
DOI: 10.1055/s-0042-106626
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© Georg Thieme Verlag KG Stuttgart · New York

Lipidsenkende Therapie in Europa und den USA

Treat to Target oder Fire and Forget?Lipid-lowering therapy in Europe and the United States – treat to target or fire and forget?
Vanessa Pfetsch*
1   Deutsches Herzzentrum München, Technische Universität München
,
Veronika Sanin*
1   Deutsches Herzzentrum München, Technische Universität München
,
Wolfgang Koenig
1   Deutsches Herzzentrum München, Technische Universität München
2   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
15. Juni 2016 (online)

Zusammenfassung

Die 2013 von der American Heart Association (AHA) und dem American College of Cardiology (ACC) vorgelegte neue Leitlinie zur Evaluation des kardiovaskulären Risikos empfiehlt eine Lipidsenkende Therapie mittels hochdosierter Statintherapie mit dem Ziel einer 30-50%-igen LDL-C-Reduktion [1]. Die Berücksichtigung eines LDL-Cholesterin (LDL-C)-Zielwertes wie sie in den europäischen Leitlinien enthalten ist, tritt in den Hintergrund. Begründet wird die Änderung der amerikanischen Leitlinien dadurch, dass für die bisher empfohlenen LDL-C-Zielwerte keine Evidenz in Form randomisierter Studien vorliege. Dieser Paradigmenwechsel führte bei den Fachgesellschaften zu kontroversen Diskussionen. Kritiker bemängeln die fehlende Möglichkeit einer Therapieevaluation oder Berücksichtigung zusätzlicher lipidmodifizierender Therapieoptionen. Die amerikanische Präventionsstrategie eines „Fire and Forget“ steht einem individualisierten, patientenorientierten europäischen Behandlungskonzept (Treat to target) gegenüber.

Abstract

The 2013 AHA/ ACC guidelines on the assessment of cardiovascular risk recommend high-dose statin treatment to reduce LDL-cholesterol (LDL-C) by at least 30-50% without suggesting a specific target value [1]. Favoring a strict Evidence Based Medicine approach the authors focus on randomized clinical trials only and neglect a target value since none of the randomized trials has titrated statin therapy to a specific LDL-C concentration. This is in contrast to current European guidelines. This paradigm shift has created a lot of controversy and confusion due to the lacking opportunity to assess medication adherence and the addition of further lipid lowering therapy. Moreover, these new guidelines might discourage clinicians to individualize patient care.

* Veronika Sanin und Vanessa Pfetsch teilen sich die Erstautorenschaft.


 
  • Literatur

  • 1 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. 2014; 63: 2889-2934
  • 2 Lewington S, Whitlock G, Clarke R et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55, 000 vascular deaths. Lancet 2007; 370: 1829-1839
  • 3 Böhm M. Positionstherapie zur Statintherapie. Clin Res Cardiol Suppl 2007; 2: 8-15
  • 4 Grundy SM, Cleeman JI, Merz CN et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110: 227-239
  • 5 Boekholdt SM, Hovingh GK, Mora S et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol 2014; 64: 485-494
  • 6 Jansen H, Samani NJ, Schunkert H. Mendelian randomization studies in coronary artery disease. European heart journal 2014; 35: 1917-1924
  • 7 Reiner Z, Catapano AL, De Backer G et al. ESC / EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; 32: 1769-1818
  • 8 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. JAMA 2012; 307: 1302-1309
  • 9 Kastelein JJ, van der Steeg WA, Holme I et al. Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation 2008; 117: 3002-3009
  • 10 Schwingshackl L, Christoph M, Hoffmann G. Effects of olive oil on markers of inflammation and endothelial function – a systematic review and meta-analysis. Nutrients 2015; 7: 7651-7675
  • 11 Casas R, Sacanella E, Urpi-Sarda M et al. The effects of the mediterranean diet on biomarkers of vascular wall inflammation and plaque vulnerability in subjects with high risk for cardiovascular disease. A randomized trial. PLoS One 2014; 9: e100084
  • 12 Estruch R, Ros E, Salas-Salvado J et al. Primary prevention of cardiovascular disease with a mediterranean diet. N Engl J Med 2013; 368: 1279-1290
  • 13 de Lorgeril M, Salen P, Martin JL et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 1999; 99: 779-785
  • 14 Tawakol A, Fayad ZA, Mogg R et al. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography / computed tomography feasibility study. J Am Coll Cardiol 2013; 62: 909-917
  • 15 Puri R, Libby P, Nissen SE et al. Long-term effects of maximally intensive statin therapy on changes in coronary atheroma composition: insights from SATURN. Eur Heart J Cardiovasc Imaging 2014; 15: 380-388
  • 16 Nicholls SJ, Ballantyne CM, Barter PJ et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011; 365: 2078-2087
  • 17 Weng TC, Yang YH, Lin SJ et al. A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharm Ther 2010; 35: 139-151
  • 18 Mukhtar RY, Reid J, Reckless JP. Pitavastatin. Int J Clin Pract 2005; 59: 239-252
  • 19 Roberts WC. The rule of 5 and the rule of 7 in lipid-lowering by statin drugs. Am J Cardiol 1997; 80: 106-107
  • 20 Cannon CP, Braunwald E, McCabe CH et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. New Engl J Med 2004; 350: 1495-1504
  • 21 Pedersen TR, Olsson AG, Faergeman O et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation 1998; 97: 1453-1460
  • 22 Simes RJ, Marschner IC, Hunt D et al. Relationship between lipid levels and clinical outcomes in the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Trial: to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels?. Circulation 2002; 105: 1162-1169
  • 23 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: 1267-1278
  • 24 Baigent C, Blackwell L, Emberson J 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: 1670-1681
  • 25 Mihaylova B, Emberson J, Blackwell L et al. 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
  • 26 Wiviott SD, Cannon CP, Morrow DA et al. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol 2005; 46: 1411-1416
  • 27 LaRosa JC, Grundy SM, Kastelein JJ et al. 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
  • 28 Hsia J, MacFadyen JG, Monyak J et al. Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol < 50 mg / dl with rosuvastatin. The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). J Am Coll Cardiol 2011; 57: 1666-1675
  • 29 Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe added to statin therapy after acute coronary syndromes. New Engl J Med 2015; 372: 2387-2397
  • 30 Stein EA, Honarpour N, Wasserman SM et al. Effect of the proprotein convertase subtilisin / kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation 2013; 128: 2113-2120
  • 31 Sabatine MS, Giugliano RP, Wiviott SD et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. New Engl J Med 2015; 372: 1500-1509
  • 32 Navarese EP, Kolodziejczak M, Schulze V et al. Effects of proprotein convertase Subtilisin / Kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis. Ann Intern Med 2015; 163: 40-51
  • 33 Robinson JG, Heistad DD, Fox KA. Atherosclerosis stabilization with PCSK-9 inhibition: an evolving concept for cardiovascular prevention. Atherosclerosis 2015; 243: 593-597
  • 34 Cannon CP, Blazing MA, Braunwald E. Ezetimibe plus a statin after acute coronary syndromes. New Engl J Med 2015; 373: 1476-1477
  • 35 Nissen SE, Tuzcu EM, Schoenhagen P 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
  • 36 Nissen SE, Tuzcu EM, Libby P et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA 2004; 292: 2217-2225
  • 37 Tardif JC, Gregoire J, L’Allier PL et al. Effects of the acyl coenzyme A: cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation 2004; 110: 3372-3377
  • 38 Nissen SE, Nicholls SJ, Wolski K et al. Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA 2008; 299: 1547-1560
  • 39 Lakoski SG, Lagace TA, Cohen JC et al. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab 2009; 94: 2537-2543
  • 40 Victor RG, Haley RW, Willett DL et al. The Dallas Heart Study: a population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health. Am J Cardiol 2004; 93: 1473-1480
  • 41 Cohen JC, Boerwinkle E, Mosley Jr TH et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. New Engl J Med 2006; 354: 1264-1272
  • 42 Zhao Z, Tuakli-Wosornu Y, Lagace TA et al. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 2006; 79: 514-523
  • 43 Hooper AJ, Marais AD, Tanyanyiwa DM et al. The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis 2007; 193: 445-448
  • 44 Robinson JG, Farnier M, Krempf M et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. New Engl J Med 2015; 372: 1489-1499
  • 45 Hirsh BJ, Smilowitz NR, Rosenson RS et al. Utilization of and adherence to guideline-recommended lipid-lowering therapy after acute coronary syndrome: opportunities for improvement. J Am Coll Cardiol 2015; 66: 184-192
  • 46 Jernberg T, Hasvold P, Henriksson M et al. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J 2015; 36: 1163-1170
  • 47 Gohlke H, Koenig W, Schunkert H et al. Stellungnahme der Deutschen Gesellschaft für Kardiologie zu den neuen US-Leitlinien zur Verminderung des Atheroskleroserisikos mittels lipidsenkender Therapie. Kardiologe 2014; DOI: 10. 1007/s12181-014–0555–2. 8: 120-124
  • 48 Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet 2013; 382: 1762-1765
  • 49 Keaney Jr JF, Curfman GD, Jarcho JA. A pragmatic view of the new cholesterol treatment guidelines. New Engl J Med 2014; 370: 275-278
  • 50 Ray KK, Kastelein JJ, Boekholdt SM et al. The ACC / AHA 2013 guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: the good the bad and the uncertain: a comparison with ESC / EAS guidelines for the management of dyslipidaemias 2011. Eur Heart J 2014; 35: 960-968
  • 51 Giugliano RP, Desai NR, Kohli P et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin / kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 2012; 380: 2007-2017
  • 52 Blom DJ, Hala T, Bolognese M et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. New England J Med 2014; 370: 1809-1819
  • 53 AHA / ACC. 2013 Prevention guideline tools – CV risk calculator. http://my.americanheart.org/cvriskcalculator (letzter Zugriff: 22.4.2016)