Download PDF
Gesundheitsökonomie & Qualitätsmanagement 2003; 8(5): 307-313
DOI: 10.1055/s-2003-43167
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Originalpräparate versus Generika - Das Beispiel Statine

ein systematischer Literaturvergleich zwischen Atorvastatin und SimvastatinStatins - Innovative Drugs versus Generic DrugsA systematic literature search on Atorvastatin and SimvastatinR. Rychlik1 , T. K. Nordt2 , S. Nelles1
  • 1Institut für Empirische Gesundheitsökonomie, Burscheid
  • 2Klinik für Herz- und Gefäßkrankheiten, Klinikum Stuttgart - Katharinenhospital
Further Information

Publication History

Publication Date:
27 October 2003 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Im Rahmen eines systematischen Literaturvergleichs wurden 62 Publikationen zum direkten Vergleich zwischen Atorvastatin und Simvastatin hinsichtlich Indikation, Dosierung (inklusive Titration), Surrogatparameter (Gesamtcholesterin, LDL, HDL, Triglyceride), Verträglichkeit, Risikofaktoren, Kosteneffektivität und Leitlinienkonformität untersucht.

Ohne Titration zeigen sich dabei Dosierungen von 10 mg Atorvastatin und 40 mg Simvastatin für Surrogatparameter als vergleichbar. Die Wirksamkeit über alle Studien ist bei beiden Substanzen bereits nach 8-12 Wochen nachweisbar. Gesamtcholesterin und LDL-C werden unter Atorvastatin stärker gesenkt, HDL-C und Triglyceride sind für beide Substanzen auch nach Titration ähnlich, lediglich bei studienübergreifender Betrachtung zeigt sich ein Vorteil für Atorvastatin.

Im direkten Vergleich von 10 mg Atorvastatin und 40 mg Simvastatin sind beide Substanzen für alle Surrogatparameter vergleichbar, die Vorgaben der internationalen Leitlinien werden mit Atorvastatin jedoch deutlich früher erreicht. Die Verträglichkeit ist als vergleichbar gut einzustufen.

Aufgrund der unterschiedlichen Leistungsprofile und fehlender Äquivalenz kann ein Kostenvergleich als Kostenminimierungsanalyse nicht erfolgen. Keinesfalls können die Preise der Packungsgrößen oder Tagestherapiekosten gegenübergestellt werden.

Damit zeigt sich, dass der Generikawettbewerb für Statine derzeit nicht zu einer Kostensenkung im deutschen Gesundheitswesen beiträgt.

Abstract

Atorvastatin and Simvastatin were compared in a systematic literature review of 62 clinical studies for claimed indication, dosage incl. titration, surrogate parameters (total cholesterol, LDL-C, HDL-C and triglycerides), safety, risk factors, cost-effectiveness and compliance with international guidelines.

When not applying dose titration, dosages of Atorvastatin 10 mg and Simvastatin 40 mg seem to be equivalent. Efficacy is reached within 8 to 12 weeks. Total cholesterol and LDL-C are reduced more with Atorvastatin, HDL-C and triglycerides are comparable for both drugs also if dosages are titrated.

Atorvastatin 10 mg and Simvastatin 40 mg reveal similar laboratory values comparing surrogate parameters. However, if international guidelines are applied, values are reached earlier with Atorvastatin.

Both, Atorvastatin and Simvastatin are safe drugs.

In terms of comparing different potential properties of both drugs, no cost-minimization analysis may be performed and prices and ddd are not applicable. As a result, at this time generic competition within the class of HMG-CoA-reductase inhibitors is not cost saving in Germany from the perspective of third party payers.

Schlüsselwörter

Generischer Wettbewerb - Atorvastatin - Simvastatin

Key words

Generic competition - Atorvastatin - Simvastatin

Literatur

  • 1 Staffa J A, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis.  N Engl J Med. 2002;  346 (7) 539-540
    CrossrefPubMedGoogle Scholar
  • 2 Schwabe U, Paffrath D. (Hrsg) .Arzneiverordnungsreport 2002,. Berlin/Heidelberg; Springer-Verlag 2003 955
    Google Scholar
  • 3 Schwabe U, Paffrath D. (Hrsg) .Arzneiverordnungsreport 2002,. Berlin/Heidelberg; Springer-Verlag 2003 789
    Google Scholar
  • 4 Dietrich E S, Schoop S, Bartmann B. et al .Arzneimitteltherapie in Deutschland - Bedarf und Realität, Eine Dokumentation der Kassenärztlichen Bundesvereinigung. Köln; Kassenärztliche Bundesvereinigung 2003
    Google Scholar
  • 5 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.  Preventive medicine. 2002;  35 (1) 48-53
    CrossrefPubMedGoogle Scholar
  • 6 Auer J, Eber B. A clinical focus on statins.  Current opinion in investigational drugs. 2001;  2 (3) 382-388
    PubMedGoogle Scholar
  • 7 Schwartz G G, Olsson A G, Ezekowitz P. et al . for the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of Atorvastatin on Early Recurrent Ischemic Events in Acute Coronary Syndromes. The MIRACL Study: A randomized controlled Trial.  The Journal of the American Medical Association. 2001;  285 1711-1718
    CrossrefPubMedGoogle Scholar
  • 8 Pitt B, Waters D, Brown W V. et al . for the Atorvastatin versus Revascularization Treatment Investigators. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease.  The New England Journal of Medicine. 1999;  341 (2) 70-76
    CrossrefPubMedGoogle Scholar
  • 9 Smilde T J, van Wissen S, Wollersheim H. et al . Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial.  The lancet. 2001;  357 577-581
    CrossrefPubMedGoogle Scholar
  • 10 National Heart Lung and Blood Institute, National Institutes of Health. Third Report of the Expert Panal on Detection, Evalution, and Treatment ot High Blood Cholesterol in Adults (adult treatment panal III) [online] Available from URL: http://www.nhlbi.nih.gov/guidelines/cholesterol/[assessed May 30 2003]. 
    Google Scholar
  • 11 Hilleman D E, Heineman S M, Foral P A. Pharmacoeconomic assessment of HMG-CoA-reductase inhibitor therapy: an analysis based on the CURVES study.  Pharmacotherapy. 2000;  20 (7) 819-822
    CrossrefPubMedGoogle Scholar
  • 12 Smith D G, McBurney C R. An Economic Analysis of the Atorastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS).  PharmacoEconomics. 2003;  21 (1) 13-23
    PubMedGoogle Scholar
  • 13 McKenney J M. The cost of treating dyslipidemia using National Cholesterol Education Program (NCEP) guidelines.  PharmacoEconomics. 1998;  14 (3) 19-28
    PubMedGoogle Scholar
  • 14 Huse D M, Russell M W, Miller J D. et al . Cost-effectiveness of statins.  The American journal of cardiology. 1998;  82 (11) 1357-1363
    CrossrefPubMedGoogle Scholar
  • 15 Farmer J A. Economic implications of lipid-lowering trials: current considerations in selecting a statin.  The American journal of cardiology. 1998;  82 (6A) 26M-31M
    CrossrefPubMedGoogle Scholar
  • 16 Olsson A G, Eriksson M, Johnson O. et al . A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: the treat-to-target (3T) study.  Clinical therapeutics. 2003;  25 (1) 119-138
    CrossrefPubMedGoogle Scholar
  • 17 Athyros V G, Papageorgiou A A, Athyrou V V. et al . Atorvastatin versus four statin-fibrate combinations in patients with familial combinated hyperlipidemia.  Journal of cardiovascular risk. 2002;  9 (1) 33-39
    CrossrefPubMedGoogle Scholar
  • 18 Branchi A, Fiorenza A M, Torri A. et al . Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia.  Clinical therapeutics. 2001;  23 (6) 851-857
    CrossrefPubMedGoogle Scholar
  • 19 Insull W, Kafonek S, Goldner D. et al . Comparison of efficacy and safety of atorvastatin (10 mg) with simvastatin (10 mg) at six weeks. ASSET Investigators.  The American journal of cardiology. 2001;  87 (5) 554-559
    CrossrefPubMedGoogle Scholar
  • 20 Joukhadar C, Klein N, Prinz M. et al . Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia.  Thrombosis and haemostasis. 2001;  85 (1) 47-51
    PubMedGoogle Scholar
  • 21 Recto C S 2nd, Acosta S, Dobs A. Comparison of the efficacy and tolerability of simvastatin and atorvastatin in the treatment of hypercholesterolemia.  Clinical cardiology. 2000;  23 (9) 682-688
    PubMedGoogle Scholar
  • 22 Hilleman D E, Heineman S M, Foral P A. Pharmacoeconomic assessment of HMG-CoA-reductase inhibitor therapy: an analysis based on the CURVES study.  Pharmaco-therapy. 2000;  20 (7) 819-822
    CrossrefPubMedGoogle Scholar
  • 23 Farnier M, Portal J J, Maigret P. Efficacy of atorvastatin compared with simvastatin in patients with hypercholesterolemia.  Journal of cardiovascular pharmacology and therapeutics. 2000;  5 (1) 27-32
    PubMedGoogle Scholar
  • 24 Branchi A, Fiorenza A M, Rovellini A. et al . Lowering effects of four different statins on serum triglyceride level.  European Journal of clinical pharmacology. 1999;  55 (7) 499-502
    CrossrefPubMedGoogle Scholar
  • 25 Badia X, Russo P, Attanasio E. A comparative economic analysis of simvastatin versus atorvastatin: results of the Surrogate Marker Cost-Efficacy (SMaC) study.  Clinical Therapeutics. 1999;  21 (10) 1788-1796
    CrossrefPubMedGoogle Scholar
  • 26 Wolfenbuttel B H, Mahla G, Muller D. et al . Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in comparison with simvastatin and pravastatin, in subjects with with hypercholesterolaemia.  The Netherlands journal of medicine. 1998;  52 (4) 131-137
    CrossrefPubMedGoogle Scholar
  • 27 Dart A, Jerums G, Nicolsin G. et al . A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolaemia.  The American journal of cardiology. 1997;  80 (1) 39-44
    CrossrefPubMedGoogle Scholar
  • 28 Huse D M, Russell M W, Miller J D. et al . Cost-effectiveness of statins.  The American journal of cardiology. 1998;  82 (11) 1357-1363
    CrossrefPubMedGoogle Scholar
  • 29 Gentile S, Turco S, Guarino G. et al . Comparative efficacy study of atorvastatin vs. simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia.  Diabetes, obesity & metabolism. 2000;  2 (6) 355-362
    PubMedGoogle Scholar
  • 30 Frolkis J P, Pearce G L, Nambi V. et al . Statins do not meet expectations for lowering low-density lipoprotein cholesterol levels when used in clinical practise.  The American journal of medicine. 2002;  113 (8) 625-629
    CrossrefPubMedGoogle Scholar
  • 31 Joukhadar C, Klein N, Prinz M. et al . Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia.  Thrombosis and haemostasis. 2001;  85 (1) 47-51
    PubMedGoogle Scholar
  • 32 Recto C S 2nd, Acosta S, Dobs A. Comparison of the efficacy and tolerability of simvastatin and atorvastatin in the treatment of hypercholesterolemia.  Clinical cardiology. 2000;  23 (9) 682-688
    PubMedGoogle Scholar
  • 33 Kastelein J J, Isaacsohn J L, Hunninhake D B. et al . Comparison of effects of simvastatin versus atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I levels.  American Journal of cardiology. 2000;  86 (2) 221-223
    CrossrefPubMedGoogle Scholar
  • 34 Hilleman D E, Heineman S M, Foral P A. Pharmacoeconomic assessment of HMG-CoA-reductase inhibitor therapy: an analysis based on the CURVES study.  Pharmaco-therapy. 2000;  20 (7) 819-822
    CrossrefPubMedGoogle Scholar
  • 35 März W, Wollschläger H, Klein G. et al . Safety of low-density lipoprotein cholesterol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial).  American Journal of Cardiology. 1999;  84 (1) 7-13
    PubMedGoogle Scholar
  • 36 Jones P, Kafonek S, Laurora I. et al . Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin and fluvastatin in patients with hypercholesterolaemia (The CURVES study).  The American journal of cardiology. 1998;  81 (5) 582-587
    CrossrefPubMedGoogle Scholar
  • 37 McKenney J M. The cost of treating dyslipidemia using National Cholesterol Education Program (NCEP) guidelines.  PharmacoEconomics. 1998;  14 (3) 19-28
    PubMedGoogle Scholar
  • 38 Farmer J A. Economic implications of lipid-lowering trials: current considerations in selecting a statin.  The American journal of cardiology. 1998;  82 (6A) 26M-31M
    CrossrefPubMedGoogle Scholar
  • 39 Wierzbicki A S, Lumb P J, Semra Y. et al . Atorvastatin compared with simvastatin-based therapies in the management of severe familial hyper lipidaemias.  Q J Med. 1999;  92 (7) 387-394
    PubMedGoogle Scholar
  • 40 Jones H J. Comparative dose efficacy of statins.  Cardiology Review. 1998;  15 (12) 25-28
    PubMedGoogle Scholar
  • 41 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.  Preventive medicine. 2002;  35 (1) 48-53
    CrossrefPubMedGoogle Scholar
  • 42 Malhotra H S, Goa K L. Atorvastatin: an updated review of its pharmacological properties and use in dyslipidaemia.  Drugs. 2001;  61 (12) 1835-1881
    CrossrefPubMedGoogle Scholar
  • 43 McKenney J M. The cost of treating dyslipidemia using National Cholesterol Education Program (NCEP) guidelines.  PharmacoEconomics. 1998;  14 (3) 19-28
    PubMedGoogle Scholar
  • 44 Wehling M. Fragwürdiges Gruppenkonzept. Wie austauschbar sind so genannte Analogpräparate? Questionable group concept. How interchangeable are so-called analog drug preparations?.  MMW Fortschritte der Medizin. 2002;  144 (46) 56-58
    PubMedGoogle Scholar
  • 45 Petersen K U. Originale und Nachahmer. Original brands and generic preparations.  Medizinische Klinik. 2000;  95 (1) 26-30
    PubMedGoogle Scholar
  • 46 King D R, Kanavos P. Encouraging the use of generic medicines: implications for transition economies.  Croatian medical journal. 2002;  43 (4) 462-469
    PubMedGoogle Scholar
  • 47 Schwabe U, Paffrath D. (Hrsg) .Arzneiverordnungsreport 2000. Berlin/Heidelberg; Springer-Verlag 2001 696
    Google Scholar
  • 48 Schwabe U, Paffrath D. (Hrsg) .Arzneiverordnungsreport 2000. Berlin/Heidelberg; Springer-Verlag 2001 697
    Google Scholar

Prof. Dr. Dr. R. Rychlik

Institut für Empirische Gesundheitsökonomie

Am Ziegelfeld 28

51399 Burscheid

Email: reinhard.rychlik@ifeg.de