Applied Health Economics and Health Policy

, Volume 10, Issue 4, pp 261–271

Economic Evaluation of Clopidogrel in Acute Coronary Syndrome Patients without ST-Segment Elevation in Greece

A Cost-Utility Analysis
  • Georgia Kourlaba
  • Vassilis Fragoulakis
  • Nikos Maniadakis
Original Research Article


Background: Current guidelines recommend treatment with antiplatelet and anticoagulant therapy for the secondary prevention of atherothrombotic events among patients with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA). The CURE (Clopidogrel in Unstable angina to prevent Recurrent Events) trial has shown that clopidogrel alone or in combination with aspirin is more effective in reducing the risk of atherothrombotic events than aspirin alone in NSTEMI or UA patients. However, in the current climate of financial constraints, the effectiveness of a treatment should be considered in conjunction with its long-term economic costs to determine the best possible care.

Objective: To evaluate the cost effectiveness of 1 year of treatment with clopidogrel in addition to aspirin in NSTEMI or UA patients from the third-party-payer perspective in Greece.

Methods: An existing Markov model consisting of six states (NSTEMI/UA/no event, first year with stroke, history of stroke, first year with myocardial infarction [MI], history of MI and death) was adapted and extended to the Greek healthcare setting for year 2012. Utility values obtained from a Greek national study were assigned to each health state in order to estimate the quality-adjusted life-years (QALYs). Costs assigned to each health state included antiplatelet treatment cost, cost for the management of adverse events and the costs for concomitant medication, hospitalization, outpatient visits, rehabilitation and nursing. Cost effectiveness and cost utility was expressed as the cost per life-year (LY) gained and QALY gained, respectively. A probabilistic sensitivity analysis was conducted.

Results: The Markov analysis predicts a discounted survival of 8.27 years in the aspirin treatment group and 8.41 years in the aspirin plus clopidogrel treatment group. The corresponding discounted QALYs were 6.88 and 7.00, respectively. The cumulated lifetime costs per patient were €18 779 and €19191, for the aspirin and aspirin plus clopidogrel treatment arms, respectively. The incremental cost-effectiveness ratio (ICER) with the addition of clopidogrel was €2951 for each LY saved and €3541 for each QALY saved. Finally, clopidogrel plus aspirin was found to be cost effective in more than 95% of simulated samples at a threshold of €7000 per discounted QALY gained.

Conclusion: One-year treatment with clopidogrel in addition to aspirin is a cost-effective treatment option for secondary prevention in patients with acute coronary syndrome without ST-segment elevation in Greece.


  1. 1.
    Steg PG, Goldberg RJ, Gore JM, et al. Baseline characteristics, management practices, and in-hospital outcomes of patients hospitalized with acute coronary syndromes in the Global Registry of Acute Coronary Events (GRACE). Am J Cardiol 2002; 90: 358–63PubMedCrossRefGoogle Scholar
  2. 2.
    Goldberg RJ, Currie K, White K, et al. Six-month outcomes in a multinational registry of patients hospitalized with an acute coronary syndrome (the Global Registry of Acute Coronary Events [GRACE]). Am J Cardiol 2004; 93: 288–93PubMedCrossRefGoogle Scholar
  3. 3.
    Pitsavos Panagiotakos DB, Antonoulas A, et al. Epidemiology of acute coronary syndromes in a Mediterranean country: aims, design and baseline characteristics of the Greek study of acute coronary syndromes (GREECS). BMC Public Health 2005; 5: 23PubMedCrossRefGoogle Scholar
  4. 4.
    Munger MA, Hawkins DW. Atherothrombosis: epidemiology, pathophysiology, and prevention. J Am Pharm Assoc 2004; 44: S5–12CrossRefGoogle Scholar
  5. 5.
    Wright RS, Anderson JL, Adams CD, et al. 2011 AC-CF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol 2011; 57: e215–367PubMedCrossRefGoogle Scholar
  6. 6.
    Hamm CW, Bassand JP, Agewall S, et al. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the task force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 2999–3054PubMedCrossRefGoogle Scholar
  7. 7.
    Ling G, Ovbiagele B. Oral antiplatelet therapy in the secondary prevention of atherothrombotic events. Am J Cardiovasc Drugs 2009; 9: 197–209PubMedCrossRefGoogle Scholar
  8. 8.
    Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324(7329): 71–86CrossRefGoogle Scholar
  9. 9.
    Collinson J, Flather MD, Fox KA, et al. Clinical outcomes, risk stratification and practice patterns of unstable angina and myocardial infarction without ST elevation: Prospective Registry of Acute Ischaemic Syndromes in the UK (PRAIS-UK). Eur Heart J 2000; 21: 1450–7PubMedCrossRefGoogle Scholar
  10. 10.
    Plavix® (clopidogrel bisulfate tablets): US prescribing information [online]. Available from URL: [Accessed 2010 Oct 08]
  11. 11.
    CAPRIE Steering Committee., A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348: 1329–39CrossRefGoogle Scholar
  12. 12.
    Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–502PubMedCrossRefGoogle Scholar
  13. 13.
    Mehta SR, Yusuf S. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial programme: rationale, design and baseline characteristics including a meta-analysis of the effects of thienopyridines in vascular disease. Eur Heart J 2000; 21: 2033–41PubMedCrossRefGoogle Scholar
  14. 14.
    Latour-Perez J, Navarro-Ruiz A, Ridao-Lopez M, et al. Using clopidogrel in non-ST-segment elevation acute coronary syndrome patients: a cost-utility analysis in Spain. Value Health 2004; 7: 52–60PubMedCrossRefGoogle Scholar
  15. 15.
    Lindgren P, Jonsson Yusuf S. Cost-effectiveness of clopidogrel in acute coronary syndromes in Sweden: a longterm model based on the CURE trial. J Intern Med 2004; 255: 562–70PubMedCrossRefGoogle Scholar
  16. 16.
    Weintraub WS, Mahoney EM, Lamy A, et al. Long-term cost-effectiveness of clopidogrel given for up to one year in patients with acute coronary syndromes without ST-segment elevation. J Am Coll Cardiol 2005; 45: 838–45PubMedCrossRefGoogle Scholar
  17. 17.
    Karnon J, Bakhai A, Brennan A, et al. A cost-utility analysis of clopidogrel in patients with non-ST-segment-elevation acute coronary syndromes in the UK. Int J Cardiol 2006; 109: 307–16PubMedCrossRefGoogle Scholar
  18. 18.
    Bruggenjurgen B, Lindgren P, Ehlken B, et al. Long-term cost-effectiveness of clopidogrel in patients with acute coronary syndrome without ST-segment elevation in Germany. Eur J Health Econ 2007; 8: 51–7PubMedCrossRefGoogle Scholar
  19. 19.
    Kolm P, Yuan Y, Veledar E, et al. Cost-effectiveness of clopidogrel in acute coronary syndromes in Canada: a long-term analysis based on the CURE trial. Can J Cardiol 2007; 23: 1037–42PubMedCrossRefGoogle Scholar
  20. 20.
    World Health Organization. Life expectancy data (2009) [online]. Available from URL: [Accessed 2012 May 02]
  21. 21.
    EUROSTAT. Causes of death by region — Crude death rate (per 100,000 inhabitants, annual data) [online]. Available from URL: [Accessed 2012 May 02]
  22. 22.
    Greek Ministry of Health. Drug price bulletin [online]. Available from URL: [Accessed 2012 Jan 11]
  23. 23.
    Kontodimopoulos N, Pappa E, Niakas D, et al. Validity of the EuroQoL (EQ-5D) instrument in a Greek general population. Value Health 2008; 11:1162–9PubMedCrossRefGoogle Scholar
  24. 24.
    Maniadakis N, Fragoulakis V, Pallis AG, et al. Economic evaluation of docetaxel-gemcitabine versus vinorelbine-cisplatin combination as front-line treatment of patients with advanced/metastatic non-small-cell lung cancer in Greece: a cost-minimization analysis. Ann Oncol 2010; 21: 1462–7PubMedCrossRefGoogle Scholar
  25. 25.
    Maniadakis N, Pallis A, Fragoulakis V, et al. Economic analysis of a multicentre, randomised, phase III trial comparing FOLFOXIRI with FOLFIRI in patients with metastatic colorectal cancer in Greece. Curr Med Res Opin 2007; 23: 2251–7PubMedCrossRefGoogle Scholar
  26. 26.
    Government Gazette. Presidential Decree 127/2005. Increase of salaries of doctors’ visits. 2005: Athens, GreeceGoogle Scholar
  27. 27.
    Government Gazette. Common Ministerial Decree Y4a/OIK.1320/1998. Definition of hospital charges. 1998: Athens, GreeceGoogle Scholar
  28. 28.
    Government Gazette. Presidential Decree 427/1991, FEK 156. Costing of medical practices. 1991: Athens, GreeceGoogle Scholar
  29. 29.
    Government Gazette. Presidential Decree 157/1991, FEK 62. Increase of salaries of doctors’ visits and medical and dental practices. 1991: Athens, GreeceGoogle Scholar
  30. 30.
    Moran JL, Solomon PJ, Peisach AR, et al. New models for old questions: generalized linear models for cost prediction. J Eval Clin Pract 2007; 13: 381–9PubMedCrossRefGoogle Scholar
  31. 31.
    Remak E, Charbonneau C, Negrier S, et al. Economic evaluation of sunitinib malate for the first-line treatment of metastatic renal cell carcinoma. J Clin Oncol 2008; 26: 3995–4000PubMedCrossRefGoogle Scholar
  32. 32.
    Briggs A, Claxton K, Sculpher M. Decision modelling for health economic evaluation. In: Gray A, Briggs A, editors. Handbooks in health economic evaluation. New York: Oxford University Press Inc., 2006Google Scholar
  33. 33.
    Barber JA, Thompson SG. Analysis of cost data in randomized trials: an application of the non-parametric bootstrap. Stat Med 2000; 19: 3219–36PubMedCrossRefGoogle Scholar
  34. 34.
    Lothgren M, Zethraeus N. Definition, interpretation and calculation of cost-effectiveness acceptability curves. Health Econ 2000; 9: 623–30PubMedCrossRefGoogle Scholar
  35. 35.
    Eichler HG, Kong SX, Gerth WC, et al. Use of cost-effectiveness analysis in health-care resource allocation decision-making: how are cost-effectiveness thresholds expected to emerge? Value Health 2004; 7: 518–28PubMedCrossRefGoogle Scholar
  36. 36.
    Tengs TO. Cost-effectiveness versus cost-utility analysis of interventions for cancer: does adjusting for health-related quality of life really matter? Value Health 2004; 7: 70–8PubMedCrossRefGoogle Scholar
  37. 37.
    Devlin N, Parkin D. Does NICE have a cost-effectiveness threshold and what other factors influence its decisions? A binary choice analysis. Health Econ 2004; 13: 437–52PubMedCrossRefGoogle Scholar
  38. 38.
    World Health Organization. WHO Commission on Macroeconomics and Health: Macroeconomics and health: investing in health for economic development. Report of the Commission on Macroeconomics and Health. Geneva: WHO, 2001Google Scholar
  39. 39.
    Murray CJ, Evans DB, Acharya A, et al. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ 2000; 9: 235–51PubMedCrossRefGoogle Scholar
  40. 40.
    Lyseng-Williamson KA, Plosker GL. Clopidogrel: a pharm-acoeconomic review of its use in patients with non-ST elevation acute coronary syndromes. Pharmacoeconomics 2006; 24: 709–26PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Georgia Kourlaba
    • 1
  • Vassilis Fragoulakis
    • 1
  • Nikos Maniadakis
    • 1
  1. 1.Department of Health Services ManagementNational School of Public HealthAthensGreece
  2. 2.National School of Public HealthAthensGreece

Personalised recommendations