The European Journal of Health Economics

, Volume 12, Issue 3, pp 253–261 | Cite as

Economic evaluation of irbesartan in combination with hydrochlorothiazide in the treatment of hypertension in Greece

  • Nikos ManiadakisEmail author
  • Mattias Ekman
  • Vasilios Fragoulakis
  • Vasiliki Papagiannopoulou
  • John Yfantopoulos
Original Paper



Hypertension is a major risk factor for cardiovascular disease and a leading cause of morbidity and mortality. This study evaluates irbesartan in relation to commonly used alternative hypertension therapies losartan and valsartan given in combination with hydrochlorothiazide (HCTZ) in the general hypertensive population in Greece.


A Markov model with eight states of health was constructed: hypertension, myocardial infarction (MI), post-MI, angina, stroke, poststroke, heart failure, and death. The model has an annual cycle and estimates mean quality-adjusted survival and treatment cost, which reflect the hypertension treatment and managing cardiovascular events. Risk functions were used to conduct extrapolations. Data on treatment effectiveness, quality of life (QOL) and epidemiology were obtained from published clinical trials and studies. The database of the main Greek National Social Insurance Institute (IKA) was analyzed to estimate the cost of events. The analysis was done from a payer perspective. All outcomes were discounted, and prices correspond to 2008.


The estimated patient cost per annum was stable angina €2,252, unstable angina €2,572, myocardial infarction €2,473, post-MI €1,677, stroke €12,233, poststroke €1,240, heart failure €2,655, coronary angiography €1,544, percutaneous transluminal coronary angioplasty €6,511, and coronary artery bypass graft surgery €11,514. For the baseline group (age 57 years, systolic blood pressure 147 mmHg, cholesterol 6.00 mmol/L, body mass index 29) of men with mild to moderate hypertension, for irbesartan, the total treatment cost was €15,146, for losartan €15,696 and for valsartan €15,613; the quality-adjusted life years (QALYs) were irbesartan 12.67, losartan 12.63 and valsartan 12.64. For the baseline group of women with mild to moderate hypertension, the total treatment cost was €12,945 for irbesartan, €13,424 for losartan and €13,379 for valsartan; QALYs were 14.29 for irbesartan, 14.27 for losartan and 14.27 for valsartan. For men with severe hypertension, for irbesartan and losartan, the total treatment cost was €18,679 and €21,488 and QALYs 12.47 and 12.37, respectively. For women, the total treatment cost was €16,202 and €19,099 and QALYs 14.16 and 14.09, respectively. Similar results were obtained in relation to other treatment groups in various sensitivity analysis scenarios.


Based on efficacy data from clinical trials and lower attainment costs in various hypertensive patient populations, irbesartan in combination with HCTZ compares favorably with losartan and valsartan in combination with HCTZ in the Greek setting.


Hypertension Angiotensin-II inhibitors Irbesartan Economic Cost Effectiveness 

JEL Classification

D61 I19 C44 C02 



This study was funded by Sanofi-Aventis Greece. The company had no involvement in the study design; collection, analysis, and interpretation of data; the writing of the manuscript; and the decision to submit it. The authors have no other conflicts of interest.


  1. 1.
    He, J., Whelton, P.K.: Epidemiology and prevention of hypertension. Med. Clin. North Am. 81, 1077–1097 (1997)PubMedCrossRefGoogle Scholar
  2. 2.
    Ezzati, M., Lopez, A.D., Rodgers, A., Vander Hoorn, S., Murray, C.J.: Selected major risk factors and global and regional burden of disease. Lancet 360, 1347–1360 (2002)PubMedCrossRefGoogle Scholar
  3. 3.
    World Health Organization, International Society of Hypertension Writing Group: 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J. Hypertens. 21, 1983–1992 (2003)CrossRefGoogle Scholar
  4. 4.
    Kearney, P., Whelton, M., Reynolds, K., Muntner, P., Whelton, P., Jiang, H.E.: Global burden of hypertension analysis of worldwide data. Lancet 365, 217–223 (2005)PubMedGoogle Scholar
  5. 5.
    Hodgson, T.A., Cai, L.: Medical care expenditures for hypertension, its complications, and its comorbidities. Med. Care 39, 599–615 (2001)PubMedCrossRefGoogle Scholar
  6. 6.
    Sanjeev, B., Thomas, J.: Incremental expenditure of treating hypertension in the United States. AJH 19, 810–816 (2006)Google Scholar
  7. 7.
    The Task force on the management of arterial hypertension of the European Society of Hypertension (ESH)and the European Society of Cardiology (ESC): 2007 Guidelines for the management of arterial hypertension. Eur. Heart J. 28, 1462–1536 (2007)Google Scholar
  8. 8.
    Anis, A.H., Sun, H., Singh, S., Woolcott, J.: A cost-utility analysis of losartan versus atenolol in the treatment of hypertension with left ventricular hypertrophy. PharmacoEconomics. 24, 387–400 (2006)PubMedCrossRefGoogle Scholar
  9. 9.
    Boersma, C., Carides, G.W., Atthobari, J., Voors, A., Jstma, M.: An economic assessment of losartan-based versus atenolol-based therapy in patients with hypertension and left-ventricular hypertrophy results from the Losartan Intervention for endpoint reduction (LIFE) study adapted to The Netherlands. Clin. Ther. 29, 963–971 (2007)PubMedCrossRefGoogle Scholar
  10. 10.
    Carides, G.W., Shahinfar, S., Dasbach, E.J.: The impact of losartan on the lifetime incidence of end-stage renal disease and costs in patients with type 2 diabetes and nephropathy. PharmacoEconomics 24, 549–558 (2006)PubMedCrossRefGoogle Scholar
  11. 11.
    Jonsson, L., Carides, G.W., Burke, T.A., Brandt, A.S., Salonen, T., Schon, S.: Cost-effective prevention of renal failure in type 2 diabetics using losartan. J. Med. Econ. 8, 131–138 (2005)CrossRefGoogle Scholar
  12. 12.
    Szucs, T.D., Burnier, M., Erne, P.: Cost-effectiveness of losartan versus atenolol in treating hypertension an analysis of the LIFE study from a Swiss perspective. Cardiovasc. Drugs Ther. 18, 391–397 (2004)PubMedCrossRefGoogle Scholar
  13. 13.
    Vora, J., Carides, G., Robinson, P.: Effects of losartan-based therapy on the incidence of end-stage renal disease and associated costs in type 2 diabetes mellitus a retrospective cost-effectiveness analysis in the United Kingdom. Curr. Ther. Res. Clin. Exp. 66, 475–485 (2005)CrossRefGoogle Scholar
  14. 14.
    Linjer, E., Hedner, T., Jönsson, B., Tord, E., Lindholm, H.L., Dahlöf, B., Ulf de Faire, Scherstén, B.: Cost analysis of different pharmacological treatment strategies in elderly hypertensives. Blood Press. 14, 107–113 (2005)PubMedCrossRefGoogle Scholar
  15. 15.
    Jonsson, B., Carides, G., Burke, T., Dasbach, E., Lindholm, L., Dahlof, B., the LIFE Study Group: Cost effectiveness of losartan in patients with hypertension and LVH an economic evaluation for Sweden of the LIFE trial. J. Hypertens. 23, 1425–1431 (2005)PubMedCrossRefGoogle Scholar
  16. 16.
    McInnes, G., Burke, T.A., Carides, G.: Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study. J. Hum. Hypertens. 20, 51–58 (2006)PubMedCrossRefGoogle Scholar
  17. 17.
    Croom, K.F., Curran, M.P., Goa, K.L., Perry, C.M.: Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy. Drugs 64, 999–1028 (2004)PubMedCrossRefGoogle Scholar
  18. 18.
    Bobrie, G., Delonca, J., Moulin, C., Giacomino, A., Postel-Vinay, N., Asmar, R.: A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations. Am. J. Hypertens. 18, 1482–1488 (2005)PubMedCrossRefGoogle Scholar
  19. 19.
    Neutel, J.M., Smith, D.: Ambulatory blood pressure comparison of the anti-hypertensive efficacy of fixed combinations of irbesartan/hydrochlorothiazide and losartan/hydrochlorothiazide in patients with mild-to-moderate hypertension. J. Int. Med. Res. 33, 620–631 (2005)PubMedGoogle Scholar
  20. 20.
    Neutel, M.J., Franklin, S.S., Oparil, S., Bhaumik, A., Ptaszynska, A., Lapuerta, P.: Efficacy and safety of irbesartan/HCTZ combination therapy as initial treatment for rapid control of severe hypertension. J. Clin. Hypertens (Greenwich) 8, 850–857 (2006)CrossRefGoogle Scholar
  21. 21.
    Salerno, C.M., Demopoulos, L., Mukherjee, R., Gradman, A.H.: Combination angiotensin receptor blocker/hydrochlorothiazide as initial therapy in the treatment of patients with severe hypertension. J. Clin. Hypertens (Greenwich) 6, 614–620 (2004)CrossRefGoogle Scholar
  22. 22.
    Neutel, J.M., Saunders, E., Bakris, G.L., Cushman, W.C., Ferdinand, K.C., Ofili, E.O., et al.: The efficacy and safety of low- and high-dose fixed combinations of irbesartan/hydrochlorothiazide in patients with uncontrolled systolic blood pressure on monotherapy: the INCLUSIVE trial. J. Clin. Hypertens (Greenwich) 7, 578–586 (2005)CrossRefGoogle Scholar
  23. 23.
    Palmer, J.A., Tucker, M.D., Valentine, J.W., Roze, S., Gabriel, S., Cordonnier, J.D.: Cost-effectiveness of irbesartan in diabetic nephropathy: a systematic review of published studies. Nephrol. Dial. Transplant. 20, 1103–1109 (2005)PubMedCrossRefGoogle Scholar
  24. 24.
    Coyle, D., Rodby, R., Soroka, S., Levin, A.: Cost-effectiveness of irbesartan 300 mg given early versus late in patients with hypertension and a history of type 2 diabetes and renal disease: a Canadian perspective. Clin. Ther. 29, 1508–1523 (2007)PubMedCrossRefGoogle Scholar
  25. 25.
    Palmer, A.J., Valentine, W.J., Ray, J.A.: Health economic implications of irbesartan treatment versus standard blood pressure control in patients with type 2 diabetes, hypertension and renal disease: a Hungarian analysis. Eur. J. Health Econ. 8, 161–168 (2007)PubMedCrossRefGoogle Scholar
  26. 26.
    Palmer, A.J., Valentine, W.J., Ray, J.A.: Irbesartan treatment of patients with type 2 diabetes, hypertension and renal disease: a UK health economics analysis. Int. J. Clin. Pract. 61, 1626–1633 (2007)PubMedCrossRefGoogle Scholar
  27. 27.
    Palmer, A.J., Valentine, W.J., Tucker, D.M., Ray, J.A.: A French cost-consequence analysis of the renoprotective benefits of irbesartan in patients with type 2 diabetes and hypertension. Curr. Med. Res. Opin. 22, 2095–2100 (2006)PubMedCrossRefGoogle Scholar
  28. 28.
    Ekman, M., Bienfait-Beuzon, C., Jackson, J.: Cost-effectiveness of irbesartan/hydrochlorothiazide in patients with hypertension: an economic evaluation for Sweden. J. Hum. Hypertens. 22, 845–855 (2008)PubMedCrossRefGoogle Scholar
  29. 29.
    Glynn, J.R., L’Italien, J.G., Sesso, D.H., Jackson, A.E., Buring, E.J.: Development of predictive models for long-term cardiovascular risk associated with systolic and diastolic blood pressure. Hypertension 39(1), 105–110 (2002)PubMedCrossRefGoogle Scholar
  30. 30.
    Kaplan, E.L., Meier, P.: Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53, 457–481 (1958)CrossRefGoogle Scholar
  31. 31.
    Ford, E.S., Giles, W.H., Croft, J.B.: Prevalence of nonfatal coronary heart disease among American adults. Am. Heart J. 139, 371–377 (2000)PubMedCrossRefGoogle Scholar
  32. 32.
    Kannel, W.B.: Incidence and epidemiology of heart failure. Heart Fail. Rev. 5, 167–173 (2000)PubMedCrossRefGoogle Scholar
  33. 33.
    Kannel, W.B., Belanger, A.J.: Epidemiology of heart failure. Am. Heart J. 121, 951–957 (1991)PubMedCrossRefGoogle Scholar
  34. 34.
    Lloyd-Jones, D.M., Larson, M.G., Leip, E.P., Beiser, A., D’Agostino, R.B., Kannel, W.B., et al.: Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Circulation. 106, 3068–3072 (2002)PubMedCrossRefGoogle Scholar
  35. 35.
    Mejhert, M., Persson, H., Edner, M., Kahan, T.: Epidemiology of heart failure in Sweden—a national survey. Eur. J. Heart Fail. 3, 97–103 (2001)PubMedCrossRefGoogle Scholar
  36. 36.
    Truelsen, T., Piechowski-Jozwiak, B., Bonita, R., Mathers, C., Bogousslavsky, J., Boysen, G.: Stroke incidence and prevalence in Europe: a review of available data. Eur. J. Neuro. 13, 581–598 (2006)CrossRefGoogle Scholar
  37. 37.
    Psaltopoulou, T., Orfanos, P., Naska, A., Lenas, D., Trichopoulos, D., Trichopoulou, A.: Prevalence, awareness, treatment and control of hypertension in a general population sample of 26, 913 adults in the Greek EPIC study. Int. J. Epidemiol. 33, 1345–1352 (2004)PubMedCrossRefGoogle Scholar
  38. 38.
    Efstratopoulos, A.D., Voyaki, S.M., Baltas, A.A., Vratsistas, F.A., Kirlas, D.E., Kontoyannis, J.T., Sakellariou, J.G., Triantaphyllou, G.B., Alokrios, G.A., Lianas, D.N., Vasilakis, E.A., Fotiadis, K.N., Kastritsea, E.E.: Prevalence, awareness, treatment and control of hypertension in Hellas, Greece: the hypertension study in general practice in Hellas (HYPERTENSHELL) national study. Am. J. Hypertens. 19, 53–56 (2006)PubMedCrossRefGoogle Scholar
  39. 39.
    Athyros, V.G., Mikhailidis, D.P., Papageorgiou, A.A., Didangelos, T.P., Ganotakis, E.S., Symeonidis, A.N., Daskalopoulou, S.S., Kakafika, A.I., Elisaf, M., the METS-GREECE Collaborative Group: Prevalence of atherosclerotic vascular disease among subjects with the metabolic syndrome with or without diabetes mellitus: the METSGREECE Multicentre Study. Curr. Med. Res. Opin. 20, 1691–1701 (2004)PubMedCrossRefGoogle Scholar
  40. 40.
    Panagiotakos, D.P., Fitzgeralns, A.P., Pitsavos, P., Pipilis, A., Graham, A., Stefanadis, C.: Statistical Modelling of 10-year fatal cardiovascular disease in Greece: The HellenicSCORE (a Calibration of the ESC SCORE Project. Hellenic J. Cardiol. 48, 55–63 (2007)PubMedGoogle Scholar
  41. 41.
    Burström, K., Johannesson, M., Diderichsen, F.: Swedish population health-related quality of life results using the EQ-5D. Qual. Life Res. 10, 621–635 (2001)PubMedCrossRefGoogle Scholar
  42. 42.
    Tengs, T.O., Lin, T.H.: A meta-analysis of quality-of-life estimates for stroke. Pharmacoeconomics 21, 191–200 (2003)PubMedCrossRefGoogle Scholar
  43. 43.
    Kirsch, J., McGuire, A.: Establishing health state valuations for disease specific states: an example from heart disease. Health Econ. 9, 149–158 (2000)PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Nikos Maniadakis
    • 1
    Email author
  • Mattias Ekman
    • 2
  • Vasilios Fragoulakis
    • 1
  • Vasiliki Papagiannopoulou
    • 3
  • John Yfantopoulos
    • 3
  1. 1.Department of Health Services ManagementNational School of Public HealthAthensGreece
  2. 2.StockholmSweden
  3. 3.Department of Health EconomicsNational Centre for Social ResearchAthensGreece

Personalised recommendations