Dtsch Med Wochenschr 2012; 137(40): 2047-2052
DOI: 10.1055/s-0032-1327203
Prävention & Versorgungsforschung | Review article
Versorgungsforschung, Fettstoffwechselstörungen
© Georg Thieme Verlag KG Stuttgart · New York

Lipidtherapie im Alltag

Leitliniengerechtes Lipidmanagement bei Patienten mit hohem kardiovaskulärem Risiko in der klinischen Praxis (LIMA Register)Lipid therapy in daily routineGuidelines compatible lipid management of patients with high cardiovascular risk in clinical practice (LIMA registry)
F. Sonntag
1   Facharztpraxis für Innere Medizin, Henstedt-Ulzburg
,
J. R. Schaefer
2   Dr. Pohl Stiftungsprofessur für Präventive Kardiologie, Innere Medizin – Kardiologie, Universitätsklinikum Gießen und Marburg, Philipps-Universität, Marburg/Lahn
,
A. K. Gitt
3   Stiftung Institut für Herzinfarktforschung an der Universität Heidelberg, c/o Klinikum Ludwigshafen, Ludwigshafen
,
A. Weizel
4   Vorsitzender der Deutschen Gesellschaft für Fettstoffwechselstörungen und deren Folgeerkrankungen (Lipid-Liga) e.V., München
,
C. Jannowitz
5   Medizinische Abteilung, MSD Sharp & Dohme GmbH, Haar
,
B. Karmann
5   Medizinische Abteilung, MSD Sharp & Dohme GmbH, Haar
,
D. Pittrow
6   Institut für Klinische Pharmakologie, Technische Universität Carl Gustav Carus, Dresden
,
K. Bestehorn
6   Institut für Klinische Pharmakologie, Technische Universität Carl Gustav Carus, Dresden
› Author Affiliations
Further Information

Publication History

23 May 2012

13 September 2012

Publication Date:
28 September 2012 (online)

Zusammenfassung

Patienten mit einem erhöhten kardiovaskulären Risiko sind in der klinischen Praxis häufig. Eine umfassende Behandlung der modifizierbaren Risikofaktoren, insbesondere der Dyslipidämie, ist erforderlich. Zahlreiche Studien in der hausärztlichen Praxis haben die Diskrepanz zwischen den Empfehlungen der einschlägigen Leitlinien und der tatsächlich erreichten Therapieeinstellung herausgearbeitet. Aktuelle Daten zur Behandlungssituation von Patienten mit hohem kardiovaskulären Risiko liefert das prospektive Register LIMA, in das niedergelassene Ärzte in 2387 Praxen in Deutschland insgesamt 13942 Patienten mit koronarer Herzkrankheit (KHK), Diabetes mellitus oder peripherer arterieller Verschlusskrankheit (PAVK) einschlossen. Die Vorbehandlung mit Simvastatin 40 mg/d war ein Einschlusskriterium. Die Ärzte dokumentierten die Arzneimittelanwendung, Laborwerte (Lipide, Blutzucker), Blutdruck und klinische Ereignisse über 1 Jahr, und erhielten nach Dateneingabe Informationen über die Zielwerterreichung ihrer Patienten. Im Mittel waren die Patienten 65,7 Jahre alt, und in 61,6 % Männer. KHK wurde in 70,6 % berichtet, Diabetes mellitus in 58,2 % und PAVK bei 14,9 %. Die meisten Patienten (68 %) erhielten auch nach der Eingangsdokumentation weiterhin Simvastatin als Monotherapie; 20,6 % der Patienten erhielten zusätzlich den Cholesterinabsorptionshemmer Ezetimib in den ersten 6 Monaten, und 23.3 % der Patienten in den zweiten 6 Monaten. Die Patienten erreichten den LDL-Cholesterin-Zielwert in 31,8 % zu Beginn und in 50,0 % nach einem Jahr. Den Blutdruckzielwert < 140 /90 mmHg erreichten 65,8 % nach 1 Jahr. Von den Patienten mit Diabetes mellitus erreichten 40,0 % einen HbA1c-Wert unter 6,5 %. Klinische Ereignisse (Tod, Krankenhauseinweisung, (kardio-)vaskuläre Ereignisse, Dialyse) traten in 11,7 % der Patienten zwischen Beginn und Monat 6, und in 12,0 % zwischen Monat 7 und 12 auf. In der täglichen Praxis bleibt die umfassende Einstellung der Risikofaktoren von Patienten mit hohem kardiovaskulären Risiko eine Herausforderung. Zur Normalisierung erhöhter LDL- Cholesterinwerte wird Ezetimib zu einer bestehenden Statintherapie hinzugefügt, was die Aussichten der Patienten für die Erreichung der Zielwerte verbessert.

Abstract

Patients with increased cardiovascular risk profile are frequently seen in general practice. Comprehensive management of modifiable risk factors, in particular dyslipidemia, is mandatory. Many studies in clinical practice have shown a gap between the recommendations in clinical guidelines and the actual situation. Current data on the management situation of patients with high cardiovascular risk is provided by the prospective registry LIMA. Primary care physicians in 2,387 offices throughout Germany documented 13,924 patients with coronary artery disease (CAD), diabetes mellitus or peripheral arterial disease (PAD). Treatment with simvastatin 40 mg was an inclusion criterion. Physicians documented drug utilization, laboratory values (lipids, blood glucose), blood pressure and clinical events over one year and received feedback about the target value attainment of their patients after data entry. Mean age of the patients was 65.7 years, and 61.6 % were men. CAD was reported in 70.6 %, diabetes mellitus in 58.2 % and PAD in 14.9 %. Most patients (68 %) received simvastatin as monotherapy also after the inclusion visit; 20.6 % of patients received in addition the cholesterol absorption inhibitor (ezetimibe) in the first 6 months, and 23.3 % in the second 6 months. Patients achieved the LDL-cholesterol target value in 31.8 % at entry and 50.0 % after one year. The blood pressure target < 140 /90 mmHg was reached by 65.8 % after one year. Of patients with diabetes mellitus 40.0 % reached an HbA1c value below 6.5 %. Clinical events (death, hospitalization, (cardio-) vascular events, and dialysis) were reported by 11.7 % of patients between entry and Month 6, and by 12.0 % between Month 7 and 12. In daily practice comprehensive management of risk factors in patients at high cardiovascular risk remains a challenge. For normalization of increased LDL cholesterol values addition of ezetimibe to existing statin therapy improves the chances of patients for target level attainment.

 
  • Literatur

  • 1 Anand SS, Yusuf S. Stemming the global tsunami of cardiovascular disease. Lancet 2011; 377: 529-532
  • 2 Armitage J, Bowman L, Wallendszus K et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 2010; 376: 1658-1669
  • 3 Assmann G, Benecke H, Neiss A et al. Gap between guidelines and practice: attainment of treatment targets in patients with primary hypercholesterolemia starting statin therapy. Results of the 4E-Registry (Efficacy Calculation and Measurement of Cardiovascular and Cerebrovascular Events Including Physicians' Experience and Evaluation). Eur J Cardiovasc Prev Rehabil 2006; 13: 776-783
  • 4 Baessler A, Fischer M, Huf V et al. Failure to achieve recommended LDL cholesterol levels by suboptimal statin therapy relates to elevated cardiac event rates. Int J Cardiol 2005; 101: 293-298
  • 5 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
  • 6 Becker RC, Meade TW, Berger PB et al. The Primary and Secondary Prevention of Coronary Artery Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 776S-814
  • 7 Berry JD, Dyer A, Cai X et al. Lifetime risks of cardiovascular disease. N Engl J Med 2012; 366: 321-329
  • 8 Bertoni AG, Bonds DE, Chen H et al. Impact of a multifaceted intervention on cholesterol management in primary care practices: guideline adherence for heart health randomized trial. Arch Intern Med 2009; 169: 678-686
  • 9 Bestehorn K, Jannowitz C, Karmann B et al. Characteristics, management and attainment of lipid target levels in patients enrolled in Disease Management Program versus those in routine care: LUTZ registry. BMC Public Health 2009; 9: 280
  • 10 Bohler S, Scharnagl H, Freisinger F et al. Unmet needs in the diagnosis and treatment of dyslipidemia in the primary care setting in Germany. Atherosclerosis 2007; 190: 397-407
  • 11 Bulbulia R, Bowman L, Wallendszus K et al. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: a randomised controlled trial. Lancet 2011; 378: 2013-2020
  • 12 Cabana MD, Rand CS, Powe NR et al. Why Don't Physicians Follow Clinical Practice Guidelines?: A Framework for Improvement. J Am Med Ass 1999; 282: 1458-1465
  • 13 Center for Disease Control and Prevention (CDC). Morbidity and Mortality Weekly Report (MMWR). QuickStats: Age-Adjusted Death Rates for Heart Disease and Cancer – United States, 1999-2009*. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6021a6.htm?s_cid=mm6021a6_w Letzter Zugriff 3.12.2011
  • 14 Danaei G, Finucane MM, Lin JK et al. National, regional, and global trends in systolic blood pressure since 1980: systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 5.4 million participants. Lancet 2011; 377: 568-577
  • 15 Diehm C, Allenberg JR, Pittrow D et al. Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic Peripheral Artery Disease. Circulation 2009; 120: 2053-2061
  • 16 Doggrell SA. The ezetimibe controversy – can this be resolved by comparing the clinical trials with simvastatin and ezetimibe alone and together?. Expert Opin Pharmacother 2012; 13: 1469-1480
  • 17 European Epidemiology Federation. Good Epidemiological Practice (GEP): Proper Conduct in Epidemiologic Research. . Updated 2007. http://www.ieaweb.org/index.php?view=article&catid=20%3Agood-epidemiological-practice-gep&id=15%3Agood-epidemiological-practice-gep&format=pdf&option=com_content&Itemid=43 Letzter Zugriff 26.06.2012
  • 18 Expert Panel on Detection E, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-2497
  • 19 Farzadfar F, Finucane MM, Danaei G et al. National, regional, and global trends in serum total cholesterol since 1980: systematic analysis of health examination surveys and epidemiological studies with 321 country-years and 3.0 million participants. Lancet 2011; 377: 578-586
  • 20 Finucane MM, Stevens GA, Cowan MJ et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 2011; 377: 557-567
  • 21 Food and Drug Administration. FDA drug safety communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. . Rockville 8 June 2011 http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm Letzter Zugriff 5.3.2012
  • 22 Geller JC, Cassens S, Brosz M et al. Achievement of guideline-defined treatment goals in primary care: the German Coronary Risk Management (CoRiMa) study. Eur Heart J 2007; ehm520
  • 23 Gitt AK, Juenger C, Jannowitz C et al. Guideline-oriented ambulatory lipid-lowering therapy of patients at high risk for cardiovascular events by cardiologists in clinical practice: the 2L cardio registry. Eur J Cardiovasc Prev Rehabil 2009; 16: 438-444
  • 24 Gitt AK, Junger C, Smolka W et al. Prevalence and overlap of different lipid abnormalities in statin-treated patients at high cardiovascular risk in clinical practice in Germany. Clin Res Cardiol 2010; 99: 723-733
  • 25 Goldstein LB, Adams R, Alberts MJ et al. Primary Prevention of Ischemic Stroke. A Guideline From the American Heart Association/American Stroke Association Stroke Council. Stroke 2006; 01.STR.0000223048.0000270103.F0000223041
  • 26 Greenland P, Alpert JS, Beller GA et al. 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol 2010; 56: 2182-2199
  • 27 Klose G, Schwabe U. Lipidsenkende Mittel. : Arzneiverordnungs-Report 2010. Berlin: Springer; 2010: 671
  • 28 Krone W, Böhm M, Wöhrmann A et al. Erhebung und Verbesserung der Behandlungssituation von Patienten mit Diabetes mellitus. Das DUTY-Register. Bundesgesundheitsblatt – Gesundheitsforschung – Gesundheitsschutz 2004; 47: 540-546
  • 29 Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. Brit Med J 2003; 326: 1423-1430
  • 30 Lloyd-Jones D, Adams RJ, Brown TM et al. Heart disease and stroke statistics – 2010 update: a report from the American Heart Association. Circulation 2010; 121: e46-e215
  • 31 Lloyd-Jones DM, Hong Y, Labarthe D et al. Defining and Setting National Goals for Cardiovascular Health Promotion and Disease Reduction. Circulation 2010; 121: 586-613
  • 32 Mancia G, De Backer G, Dominiczak A et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007; 28: 1462-1536
  • 33 Mikhailidis DP, Lawson RW, McCormick AL et al. Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis. Curr Med Res Opin 2011; 27: 1191-1210
  • 34 Mikhailidis DP, Sibbring GC, Ballantyne CM et al. Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy. Curr Med Res Opin 2007; 23: 2009-2026
  • 35 Pearson TA, Denke MA, McBride PE et al. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial. Mayo Clin Proc 2005; 80: 587-595
  • 36 Pittrow D, Pieper L, Klotsche J (Hrsg.) DETECT. Ergebnisse einer klinisch-epidemiologischen Querschnitts- und Verlaufsstudie mit 50.000 Patienten in 3.000 Hausarztpraxen. München: Elsevier; 2007
  • 37 Ruof J, Klein G, März W et al. Lipid-lowering medication for secondary prevention of coronary heart disease in a German outpatient population: the gap between treatment guidelines and real life treatment patterns. Prev Med 2002; 35: 48-53
  • 38 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 2008; 117: 1945-1954
  • 39 Smith Jr SC, Allen J, Blair SN 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. Circulation 2006; 113: 2363-2372
  • 40 Toth PP, Morrone D, Weintraub WS et al. Safety profile of statins alone or combined with ezetimibe: a pooled analysis of 27 studies including over 22,000 patients treated for 6-24 weeks. Int J Clin Pract 2012; 66: 800-812
  • 41 Yusuf S, Hawken S, Ounpuu S et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937-952