American Journal of Cardiovascular Drugs

, Volume 10, Issue 6, pp 369–382

The Cost Effectiveness of Statin Therapies in Spain in 2010, after the Introduction of Generics and Reference Prices

Original Research Article



HMG-CoA reductase inhibitors (statins) are the first-line drugs for use in the reduction of low-density lipoprotein cholesterol (LDL-C) levels and prevention of coronary heart disease (CHD) in patients with hypercholesterolemia. Generic statins could change the cost effectiveness of statin therapies in Spain, and more population groups could be included in the recommendations for reduction of cholesterol levels based on cost effectiveness.


The objectives of this study were: (i) to assess the cost effectiveness of available statins for the reduction of LDL-C levels in Spain in 2010, after the introduction of generics and reference prices; (ii) to assess the cost effectiveness of combination therapy using a statin plus cholestyramine or ezetimibe; and (iii) to estimate the mean cost per patient to achieve National Cholesterol Education Program (Adult Treatment Panel-III) therapeutic objectives.


The following treatments were evaluated: rosuvastatin 5–20mg/day; atorvastatin, simvastatin, and pravastatin 10–40mg/day; lovastatin and fluvastatin 20–80mg/day; and combination therapy with a statin plus either cholestyramine 12–24g/day or ezetimibe 10mg/day. The cost effectiveness was evaluated in terms of cost per percentage point reduction in LDL-C, comparing the annual treatment costs with the effectiveness in reducing LDL-C. Treatment costs included those for medications (2010 wholesale prices), control measures, and treatment of adverse drug effects. The effectiveness of statins was estimated by developing a meta-analysis of clinical trials published between 1993 and 2005 that met several inclusion criteria. Average and incremental cost-effectiveness ratios were calculated to assess the efficiency of individual statin and combination therapies in reducing LDL-C levels.


The effectiveness in terms of percentage reduction in LDL-C ranged from 19% for pravastatin 10mg/day to 55% for atorvastatin 80mg/day. Annual treatment costs ranged from €189.7 for simvastatin 10mg/day to €759.3 for atorvastatin 80mg/day. The cost-effectiveness ratios, in terms of cost per percentage point reduction in LDL-C, were: €6 for simvastatin, €10–12 for rosuvastatin, €10 for lovastatin, €13–16 for atorvastatin, €13–14 for fluvastatin, and €14–20 for pravastatin. Rosuvastatin + ezetimibe, simvastatin + ezetimibe, and atorvastatin + ezetimibe were the most cost-effective combination therapies for reducing LDL-C levels. Rosuvastatin was the most cost-effective statin for achieving the LDL-C therapeutic goal in patients at high risk for CHD, with a mean cost per patient of €516. Simvastatin was the most cost-effective statin to achieve the LDL-C goal in patients with moderate or low CHD risk, with a cost per patient of €217 and €190, respectively.


Rosuvastatin should be the first-choice agent in patients with high CHD risk, while simvastatin should be the first choice in patients with moderate or low risk. The addition of ezetimibe to rosuvastatin, simvastatin, or atorvastatin should be the preferred combination therapies when greater LDL-C reductions are required. The cost effectiveness of all statin therapies has increased in Spain after the introduction of generic statins and reference prices.


  1. 1.
    Nationa Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel-III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATP-III). JAMA 2001; 285: 2486–97.CrossRefGoogle Scholar
  2. 2.
    Plans-Rubió P. Cost-effectiveness of pharmacological therapies to reduce LDL-C levels. In: Pagano IS, Strait NB, editors. HDL and LDL cholesterol: physiology and clinical significance. New York (NY): Nova Biomedical Books, 2009.Google Scholar
  3. 3.
    Hilleman DE, Phillips JO, Mohiuddin SM, et al. A population-based treat-to-target pharmacoeconomic analysis of HMG-CoA reductase inhibitors in hypercholesterolemia. Clin Thera 1999; 21: 536–62.CrossRefGoogle Scholar
  4. 4.
    Tran BL, Frial T, Miller PSJ. Statin’s cost-effectiveness: a Canadian analysis of commonly used prescribed generic and brand name statins. Can J Clin Pharmacol 2007; 14: 205–14.Google Scholar
  5. 5.
    Plans-Rubió P. Cost-effectiveness analysis of cholesterol-lowering therapies in Spain. Am J Cardiovascular Drugs 2006; 6: 177–88.CrossRefGoogle Scholar
  6. 6.
    Plan Rubió P. Impacto sobre el sistema sanitario catalán de la aplicación de las recomendaciones del segundo y tercer informes del National Cholesterol Education Program (ATP-II y ATP-III) sobre prevención y control de la hipercolesterolemia en adultos. Clin Invest Arterioscl 2003; 15: 43–52.Google Scholar
  7. 7.
    Ministerio de Sanidad y Consumo (Spain). Principios activos de mayor consumo en el Sistema Nacional de Salud durante 2007. Información Terapéutica del Sistema Nacional de Salud 2008; 32: 99–100.Google Scholar
  8. 8.
    Ministerio de Sanidad y Consumo (Spain). Grupos terapéuticos y principios activos de mayor consumo en el Sistema Nacional de Salud durante 2003. Información Terapéutica del Sistema Nacional de Salud 2004; 28: 121–4.Google Scholar
  9. 9.
    López-Casasnovas G, Puig-Junoy J. Review of the literature on reference pricing. Health Policy 2000; 54: 87–123.PubMedCrossRefGoogle Scholar
  10. 10.
    Vademecum Internacional. Madrid: Medicom SA, 2010.Google Scholar
  11. 11.
    COMB. Nomenclator, 2010. COMB, Barcelona, 2010.Google Scholar
  12. 12.
    García-Rodríguez LA, Luján Massó-González E, Wallander MA, et al. The safety of rosuvastatin in comparison with other statins in over 100 000 statin users in UK primary care. Pharmacol Drug Saf 2008; 17: 943–52.CrossRefGoogle Scholar
  13. 13.
    Harinder SM, Goa KL. Atorvastatin: an updated review of its pharmacological properties and use in dyslipidaemia. Drugs 2007; 61: 1835–81.Google Scholar
  14. 14.
    Haria M, NcTavish D. Pravastatin: a reappraisal of its pharmacological properties and clinical effectiveness in the management of coronary heart disease. Drugs 1997; 53: 299–336.PubMedCrossRefGoogle Scholar
  15. 15.
    Langtry HD, Markham A. Fluvastatin: a review of its use in lipid disorders. Drugs 1999; 57: 583–606.PubMedCrossRefGoogle Scholar
  16. 16.
    Newman C, Tsai J, Szarek M, et al. Comparative safety of atorvastatin 80mg versus 10mg derived from analysis of 49 completed trials in 14,236 patients. Am J Cardiol 2006; 97: 61–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Henwood UM, Heel RC. Lovastatin. A preliminary review of its pharmaco-dynamic properties and therapeutic use in hyperlipidaemia. Drugs 1988; 36: 429–54.PubMedCrossRefGoogle Scholar
  18. 18.
    Higgins JPT, Thomson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. Br Med J 2009; 327: 557–60.CrossRefGoogle Scholar
  19. 19.
    Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR trial). Am J Cardiol 2003; 92: 152–60.PubMedCrossRefGoogle Scholar
  20. 20.
    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. Br Med J 2003; 326: 1423–9.CrossRefGoogle Scholar
  21. 21.
    Briggs A. Handling uncertainty in economic evaluations and presenting the results. In: Drummond M, McGuire A, editors. Economic evaluation in health care. Oxford: Oxford University Press, 2001: 172–214.Google Scholar
  22. 22.
    Johannesson M, Weinstein MC. On decision rules of cost-effectiveness analysis. J Health Econom 1993; 12:459–67.CrossRefGoogle Scholar
  23. 23.
    Schulman KA, Kinosian B, Jacobson TA, et al. Reducing high blood cholesterol level with drugs: cost-effectiveness of pharmacologic management. JAMA 1991; 265: 1949–50.Google Scholar
  24. 24.
    Kastelein JJP, Akdim F, Stroes ESG, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. New Engl J Med 2008; 358: 1431–43.PubMedCrossRefGoogle Scholar
  25. 25.
    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: 1453–60.PubMedCrossRefGoogle Scholar
  26. 26.
    Shepherd J, Cobe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333: 1301–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Heinonen TM, Stein E, Weiss SR, et al. The lipid-lowering effects of atorvastatin, a new HMG-CoA reductase inhibitor: results of a randomized, double-masked study. Clin Ther 1996; 18: 853–63.PubMedCrossRefGoogle Scholar
  28. 28.
    Andrews TC, Ballantyne CM, Hsia JA, et al. Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins. Am J Med 2001; 111: 185–91.PubMedCrossRefGoogle Scholar
  29. 29.
    Karalis DG, Ross AM, Vacari RM, et al. Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease. Am J Cardiol 2002; 89: 667–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Olsson AG, Eriksson M, Johnson O, et al., 3T Study Investigators. 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. Clin Ther 2003; 25: 119–38.PubMedCrossRefGoogle Scholar
  31. 31.
    Bakker-Arkema RG, Best J, Fayyad R, et al. A brief review paper of the efficacy and safety of atorvastatin in early clinical trials. Atherosclerosis 1997; 131:17–23.PubMedCrossRefGoogle Scholar
  32. 32.
    Japan Cholesterol Lowering Atorvastatin Study (J-CLAS) Group. Efficacy of atorvastatin in primary hypercholesterolemia. Am J Cardiol 1997; 79:1248–52.CrossRefGoogle Scholar
  33. 33.
    Nawrocki JW, Weiss SR, Davidson MH, et al. Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor. Arterioscler Thromb Vasc Biol 1995; 15: 678–82.PubMedCrossRefGoogle Scholar
  34. 34.
    Branchi A, Fiorenza AM, Rovellini A, et al. Lowering effects of four different statins on serum triglyceride level. Eur J Clin Pharmacol 1999; 55: 499–502.PubMedCrossRefGoogle Scholar
  35. 35.
    Black DM, Bakker-Arkema R, Heinonen T, et al. Does the presence of either concurrent hypertension or non-insulin-dependent diabetes mellitus affect the efficacy and safety of atorvastatin in patients with hypercholesterolemia? Am J Hypertens 1998; 11:75–9.CrossRefGoogle Scholar
  36. 36.
    Illingworth DR, Tobert JA. A review of clinical trials comparing HMG-CoA reductase inhibitors. Clin Ther 1994; 16: 366–85.PubMedGoogle Scholar
  37. 37.
    The Simvastatin Pravastatin Study Group. Comparison of the efficacy, safety and tolerability of simvastatin and pravastatin for hypercholesterolemia. Am J Cardiol 1993; 71: 1408–14.CrossRefGoogle Scholar
  38. 38.
    Farmer JA, Washington LC, Jones PH, et al. Comparative effects of simvastatin and lovastatin in patients with hypercholesterolemia. The Simvastatin and Lovastatin Multicenter Study Participants. Clin Ther 1992; 14: 708–17.PubMedGoogle Scholar
  39. 39.
    Jacotot B, Benghozi R, Pfister P, et al. Comparison of fluvastatin versus pravastatin treatment of primary hypercholesterolemia. French Fluvastatin Study Group. Am J Cardiol 1995; 76: 54A–6A.PubMedCrossRefGoogle Scholar
  40. 40.
    Dart A, Jerums G, Nicholson G, et al. A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia. Am J Cardiol 1997; 80: 39–44.PubMedCrossRefGoogle Scholar
  41. 41.
    Keech A, Collins R, MacMahon S, et al. Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study. Eur Heart J 1994; 15: 255–69.PubMedCrossRefGoogle Scholar
  42. 42.
    Jula A, Marniemi J, Huupponen R, et al. Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial. JAMA 2002; 287: 598–605.PubMedCrossRefGoogle Scholar
  43. 43.
    Brown WV, Bays HE, Hassman DR, et al. Rosuvastatin Study Group: effectiveness and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia: a randomized, double-blind, 52-week trial. Am Heart J 2002; 144: 1036–43.PubMedCrossRefGoogle Scholar
  44. 44.
    Ose L, Davidson MH, Stein EA, et al. Lipid-altering efficacy and safety of simvastatin 80mg/day: long-term experience in a large group of patients with hypercholesterolemia. World Wide Expanded Dose Simvastatin Study Group. Clin Cardiol 2000; 23: 39–46.PubMedCrossRefGoogle Scholar
  45. 45.
    The Lovastatin Pravastatin Study Group. A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia. Am J Cardiol 1993; 71: 810–5.CrossRefGoogle Scholar
  46. 46.
    Banga JD, Jacotot B, Pfister P, et al. Long-term treatment of hypercholesterolemia with fluvastatin: a 52-week multicenter safety and efficacy study. French-Dutch Fluvastatin Study Group. Am J Med 1994; 96: 87S–93S.PubMedCrossRefGoogle Scholar
  47. 47.
    Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Lewis SJ, Sacks FM, Mitchell JS, et al. Effect of pravastatin on cardiovascular events in women after myocardial infarction: the cholesterol and recurrent events (CARE) trial. J Am Coll Cardiol 1998; 32: 140–6.PubMedCrossRefGoogle Scholar
  49. 49.
    The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349–57.CrossRefGoogle Scholar
  50. 50.
    Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360: 1623–30.PubMedCrossRefGoogle Scholar
  51. 51.
    Prisant LM, Downton M, Watkins LO, et al. Efficacy and tolerability of lovastatin in 459 African-Americans with hypercholesterolemia. Am J Cardiol 1996; 78: 420–4.PubMedCrossRefGoogle Scholar
  52. 52.
    Castano G, Menendez R, Mas R, et al. Effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia associated with type 2 diabetes mellitus. Int J Clin Pharmacol Res 2002; 22: 89–99.PubMedGoogle Scholar
  53. 53.
    Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med 1991; 151: 43–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Davidson M, McKenney J, Stein E, et al. Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I. Am J Cardiol 1997; 79: 1475–81.PubMedCrossRefGoogle Scholar
  55. 55.
    Rindone JP, Hiller D, Arriola G. A comparison of fluvastatin 40mg every other day versus 20mg every day in patients with hypercholesterolemia. Pharmacotherapy 1998; 18: 836–9.PubMedGoogle Scholar
  56. 56.
    Herd JA, Ballantyne CM, Farmer JA, et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am J Cardiol 1997; 80: 278–86.PubMedCrossRefGoogle Scholar
  57. 57.
    Malhotra HS, Goa KL. Atorvastatin: an updated review of its pharmacological properties and use in dyslipidaemia. Drugs 2001; 61: 1835–81.PubMedCrossRefGoogle Scholar
  58. 58.
    Zavoral JH, Haggerty BJ, Winick AG, et al. Efficacy of fluvastatin, a totally synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. FLUENT Study Group. Fluvastatin Long-Term Extension Trial. Am J Cardiol 1995; 76: 37A–40A.PubMedCrossRefGoogle Scholar
  59. 59.
    Jacotot B, Banga JD, Waite R, et al. Long-term efficacy with fluvastatin as monotherapy and combined with cholestyramine (a 156-week multicenter study). French-Dutch Fluvastatin Study Group. Am J Cardiol 1995; 76 (Suppl.): 41A–46A.PubMedCrossRefGoogle Scholar
  60. 60.
    Peters TK, Muratti EN, Mehra M. Fluvastatin in primary hypercholesterolemia: efficacy and safety in patients at high risk. An analysis of a clinical trial database. Am J Med 1994; 96: 79S–83S.PubMedCrossRefGoogle Scholar
  61. 61.
    Peters TK. Fluvastatin in severe hypercholesterolemia: analysis of a clinical trial database. Am J Cardiol 1995; 76: 71A–5A.PubMedCrossRefGoogle Scholar
  62. 62.
    Serruys PW, Foley DP, Jackson G, et al. A randomized placebo-controlled trial of fluvastatin for prevention of restenosis after succesful coronary balloon angioplasty: final results of the fluvastatin angiographic restenosis (FLARE) trial. Eur Heart J 1998; 20: 58–69.CrossRefGoogle Scholar
  63. 63.
    Blum CB. Comparison and properties of four inhibitors of 3-hydroxy-3-methylglutaril-coenzyme A reductase. Am J Cardiol 1994; 73: 3D–11D.PubMedCrossRefGoogle Scholar
  64. 64.
    Drazen JM, Jarcho JA, Morrissey S, et al. Cholesterol lowering and ezetimibe. New Engl J Med 2008; 358: 1507–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Koren MJ, Smith DG, Hunninghake DB et al. The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolemic patients: a comparison of atorvastatin, simvastatin, lovastatin and fluvastatin. Pharmacoeconomics 1998; 14: 59–70.PubMedCrossRefGoogle Scholar
  66. 66.
    MacLaine GDH, Patel H. A cost-effectiveness model of alternative statins to achieve target LDL-C levels. Int J Clin Pract 2001; 55: 243–9.PubMedGoogle Scholar
  67. 67.
    Benner JS, Smith TW, Klingman D, et al. Cost-effectiveness of rosuvastatin compared with other statins from a managed care perspective. Value Health 2005; 8: 618–28.PubMedCrossRefGoogle Scholar
  68. 68.
    Gouveia Pinto C, Oliveira Carrageta M, Silva Miguel L. Cost-effectiveness of rosuvastatin in the prevention of ischemic heart disease in Portugal. Value Health 2008; 11: 154–9.CrossRefGoogle Scholar
  69. 69.
    Zweifel P, Crivelli L. Price regulation of drugs: lessons from Germany. J Regulatory Economics 1996; 10: 257–73.CrossRefGoogle Scholar
  70. 70.
    Giuliani G, Selke G, Garattini L. The German experience in reference pricing. Health Policy 1998; 44: 73–85.PubMedCrossRefGoogle Scholar
  71. 71.
    Puig-Junoy J. The impact of reference pricing interventions in the statin market. Health Policy 2007; 84: 14–29.PubMedCrossRefGoogle Scholar
  72. 72.
    Farmaindustria. El mercado del medicamento en España. Boletin de Coyuntura 2006; 11: 1–2.Google Scholar
  73. 73.
    Higgins MJ, Graham SJH. Balancing innovation and access: patent challenges tip the scales. Science 2009; 326: 370–1.PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2010

Authors and Affiliations

  1. 1.General Directorate of Public Health, Health DepartamentHealth RegistriesBarcelonaSpain

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