PDF herunterladen
Thromb Haemost 2014; 111(01): 103-110
DOI: 10.1160/TH13-07-0557
Platelets and Blood Cells
Schattauer GmbH

Universal versus platelet reactivity assay-driven use of P2Y12 inhibitors in acute coronary syndrome patients

Cost-effectiveness analyses for six European perspectives
Craig I. Coleman
1   University of Connecticut School of Pharmacy, Storrs, Conneticut, USA
,
Brendan L. Limone
1   University of Connecticut School of Pharmacy, Storrs, Conneticut, USA
› Institutsangaben
Financial support: This work was supported by Accumetrics, Inc., San Diego, California, USA. The authors maintained full control over the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation and review of the manuscript. Accumetrics, Inc. reviewed the final manuscript prior to submission. Drs. Coleman and Limone had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Weitere Informationen

Publikationsverlauf

Received: 11. Juli 2013

Accepted after major revision: 08. September 2013

Publikationsdatum:
21. November 2017 (online)

   Lizenzen und Reprints

Summary

Platelet reactivity assays (PRAs) can predict patients’ likely response to clopidogrel. As ticagrelor and prasugrel are typically considered first-line agents for acute coronary syndrome in Europe, we assessed the cost-effectiveness of universal compared to PRA-driven selection of these agents. A Markov model was used to calculate five-year costs (2013£/€), quality-adjusted life-years and incremental cost-effectiveness ratios (ICERs) for one-year of universal ticagrelor or prasugrel (given to all) compared to each agents’ corresponding PRA-driven strategy (ticagrelor/prasugrel in those with high platelet reactivity [HPR, >208 on the VerifyNow P2Y12 assay], others given generic clopidogrel). We assumed patients had their index event at 65–70 years of age and had a 42.7% incidence of HPR 24–48 hours post-revascularisation. The analysis was conducted from the perspective of six countries (France, Germany, Italy, Spain, the Netherlands and United Kingdom) and used a one-year cycle length. Event data for P2Y12 inhibitors were taken from multinational randomised trials and adjusted using country-specific epidemiologic data. Neither universal ticagrelor nor prasugrel were found to be cost-effective (all ICERs >40,250€ or £36,600/QALY) compared to their corresponding PRA-driven strategies in any of the countries evaluated. Results were sensitive to differences in P2Y12 Inhibitors costs and drug-specific relative risks of major adverse cardiac events. Monte Carlo simulation suggested universal ticagrelor or prasugrel were cost-effective in only 25–44% and 11–17% of 10,000 iterations compared to their respective PRA-driven strategies, when applying a willingness-to-pay threshold = €30,000 or £20,000/QALY. In conclusion, the universal use of newer P2Y12 inhibitors is not likely cost-effective compared to PRA-driven strategies.

Keywords

Platelet reactivity assay - acute coronary syndrome - antiplatelet agents - cost-effectiveness analysis - Markov model

 

  • References

  • 1 Hamm CW, Bassand JP, Agewall S. et al. ESC Committee for Practice Guidelines. 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: 2999-3054.
    CrossrefPubMedSuche in Google Scholar
  • 2 VerifyNow* PRUTest. Available at: http://www.accumetrics.com/verifynow-prutest . Accessed November 5, 2012.
    PubMed
  • 3 Campo G, Parrinello G, Ferraresi P. et al. Prospective evaluation of on-clopido-grel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol 2011; 57: 2474-2483.
    CrossrefPubMedSuche in Google Scholar
  • 4 Marcucci R, Gori AM, Paniccia R. et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation 2009; 119: 237-242.
    CrossrefPubMedSuche in Google Scholar
  • 5 Fileti L, Campo G, Valgimigli M. Latest clinical data on testing for high on-treatment platelet reactivity. Rev Cardiovasc Med 2011; 12 (Suppl. 01) S14-22.
    CrossrefPubMedSuche in Google Scholar
  • 6 Stone GW, Witzenbichler B, Weisz G. et al. ADAPT-DES Investigators. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-elut-ing stents (ADAPT-DES): a prospective multicentre registry study. Lancet 2013; 382: 614-623.
    CrossrefPubMedSuche in Google Scholar
  • 7 Yusuf S, Zhao F, Mehta SR. et al. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST segment elevation. N Engl J Med 2001; 345: 494-502.
    CrossrefPubMedSuche in Google Scholar
  • 8 Wallentin L, Becker RC, Budaj A, et al. PLATO Investigators. Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.
    CrossrefPubMedSuche in Google Scholar
  • 9 Wiviott SD, Braunwald E, McCabe CH. et al. TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
    CrossrefPubMedSuche in Google Scholar
  • 10 Bagust A, Boland A, Blundell M. et al. Ticagrelor for the treatment of acute coronary syndromes: A Single Technology Appraisal. LRiG, The University of Liverpool 2011
    PubMedSuche in Google Scholar
  • 11 AstraZeneca UK Ltd. Ticagrelor for the treatment of acute coronary syndromes. Single technology appraisal 2010 Available at: http://guidance.nice.org.uk/TA236 . Last accessed June 20, 2013.
    PubMedSuche in Google Scholar
  • 12 Nikolic E, Janzon M, Hauch O. et al. PLATO Health Economic Substudy Group. Cost-effectiveness of treating acute coronary syndrome patients with ti-cagrelor for 12 months: results from the PLATO study. Eur Heart J 2013; 34: 220-228.
    CrossrefPubMedSuche in Google Scholar
  • 13 Theidel U, Asseburg C, Giannitsis E. et al. Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany. Clin Res Cardiol 2013; 102: 447-458.
    CrossrefPubMedSuche in Google Scholar
  • 14 Allen LA, O’Donnell CJ, Camargo Jr. CA. et al. Comparison of long-term mortality across the spectrum of acute coronary syndromes. Am Heart J 2006; 151: 1065-1071.
    CrossrefPubMedSuche in Google Scholar
  • 15 Chevreul K, Durand-Zaleski I, Gouépo A. et al. Cost of stroke in France. Eur J Neurol 2013; 20: 1094-1100.
    CrossrefPubMedSuche in Google Scholar
  • 16 Dennis MS, Burn JP, Sandercock PA. et al. Long-term survival after first-ever stroke: the Oxfordshire Community Stroke Project. Stroke 1993; 24: 796-800.
    CrossrefPubMedSuche in Google Scholar
  • 17 Norhammar A, Stenestrand U, Lindback J. et al. Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA). Women younger than 65 years with diabetes mellitus are a high-risk group after myocardial infarction: a report from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA). Heart 2008; 94: 1565-1570.
    CrossrefPubMedSuche in Google Scholar
  • 18 Olai L, Omne-Ponten M, Borgquist L. et al. Survival, hazard function for a new event, and healthcare utilization among stroke patients over 65 years old. Stroke 2009; 40: 3585-3590.
    CrossrefPubMedSuche in Google Scholar
  • 19 Marques-Vidal P, Ruidavets JB, Cambou JP. et al. Incidence, recurrence, and case fatality rates for myocardial infarction in southwestern France, 1985 to 1993. Heart 2000; 84: 171-175.
    CrossrefPubMedSuche in Google Scholar
  • 20 Béjot Y, Rouaud O, Jacquin A. et al. Stroke in the very old: incidence, risk factors, clinical features, outcomes and access to resources-- a 22-year population-based study. Cerebrovasc Dis 2010; 29: 111-121.
    CrossrefPubMedSuche in Google Scholar
  • 21 Latour-Pérez J, Navarro-Ruiz A, Ridao-López M. et al. Using clopidogrel in non-ST-segment elevation acute coronary syndrome patients: a cost-utility analysis in Spain. Value Health 2004; 7: 52-60.
    CrossrefPubMedSuche in Google Scholar
  • 22 Robinson M, Palmer S, Sculpher M. et al. Cost effectiveness of alternative strategies for the initial medical management of non-ST elevation acute coronary syndrome: systematic review and decisionanalytical modelling. Health Technol Assess 2005; 9: iii-xi.
    CrossrefPubMedSuche in Google Scholar
  • 23 Díaz Guzmán J. Cardioembolic stroke: epidemiology. Neurología 2012; 27 (Suppl. 01) 4-9.
    CrossrefPubMedSuche in Google Scholar
  • 24 Vega T, Zurriaga O, Ramos JM. et al. Group of research for the RECENT project. Stroke in Spain: epidemiologic incidence and patterns; a health sentinel network study. J Stroke Cerebrovasc Dis 2009; 18: 11-16.
    CrossrefPubMedSuche in Google Scholar
  • 25 Fernández de Bobadilla J, Sicras-Mainar A, Navarro-Artieda R. et al. Estimation of the prevalence, incidence, comorbidities and direct costs associated to stroke patients requiring care in an area of the Spanish population. Rev Neurol 2008; 46: 397-405.
    PubMedSuche in Google Scholar
  • 26 Eurostat Harmonised Index of Consumer Prices. Available at: http://epp.euros-tat.ec.europa.eu/cache/ITY_SDDS/en/prc_hicp_esms.html . Last accessed on June 19, 2013.
    PubMed
  • 27 United Kindom Office of National Statistics. Consumer price inflation. Available at: http://www.ons.gov.uk/ons/index.html . Last accessed on June 20, 2103.
    PubMed
  • 28 Youman P, Wilson K, Harraf F. et al. The economic burden of stroke in the United Kingdom. Pharmacoeconomics 2003; 21 (Suppl. 01) 43-50.
    CrossrefPubMedSuche in Google Scholar
  • 29 Karnon J, Holmes MW, Williams R. et al. A cost-utility analysis of clopidogrel in patients with ST elevation acute coronary syndromes in the UK. Int J Cardiol 2010; 140: 315-322.
    CrossrefPubMedSuche in Google Scholar
  • 30 Crespin DJ, Federspiel JJ, Biddle AK. et al. Ticagrelor versus genotype-driven antiplatelet therapy for secondary prevention after acute coronary syndrome: a cost-effectiveness analysis. Value Health 2011; 14: 483-491.
    CrossrefPubMedSuche in Google Scholar
  • 31 Pignone M, Earnshaw S, Pletcher MJ. et al. Aspirin for the primary prevention of cardiovascular disease in women: a cost-utility analysis. Arch Intern Med 2007; 167: 290-295.
    CrossrefPubMedSuche in Google Scholar
  • 32 Augustovski FA, Cantor SB, Thach CT. et al. Aspirin for primary prevention of cardiovascular events. J Gen Intern Med 1998; 13: 824-835.
    CrossrefPubMedSuche in Google Scholar
  • 33 Meenan RT, Saha S, Chou R. et al. Cost-effectiveness of echocardiography to identify intracardiac thrombus among patients with first stroke or transient ischemic attack. Med Decis Making 2007; 27: 161-177.
    CrossrefPubMedSuche in Google Scholar
  • 34 Tengs TO, Lin TH. A meta-analysis of quality-of-life estimates for stroke. Phar-macoeconomics 2003; 21: 191-200.
    CrossrefPubMedSuche in Google Scholar
  • 35 Gold MR. Cost-Effectiveness in Health and Medicine. New York: Oxford University Press; 1996
    Suche in Google Scholar
  • 36 Husereau D, Drummond M, Petrou S. et al. CHEERS Task Force. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Br Med J 2013; 346: f1049
    CrossrefPubMedSuche in Google Scholar
  • 37 Collet JP, Cuisset T, Rangé G. et al. ARCTIC Investigators. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367: 2100-2109.
    CrossrefPubMedSuche in Google Scholar
  • 38 Sardella G, Calcagno S, Mancone M. et al. Pharmacodynamic effect of switching therapy in patients with high on-treatment platelet reactivity and genotype variation with high clopidogrel dose versus prasugrel: the RESET GENE trial. Circ Cardiovasc Interv 2012; 5: 698e704
    CrossrefPubMedSuche in Google Scholar
  • 39 Price MJ, Berger PB, Teirstein PS. et al. GRAVITAS Investigators. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. J Am Med Assoc 2011; 305: 1097-1105.
    CrossrefPubMedSuche in Google Scholar
  • 40 Coleman CI, Limone BL. Cost-Effectiveness of universal and platelet reactivity assay-driven antiplatelet therapy in acute coronary syndrome. Am J Cardiol 2013; 112: 355-362.
    CrossrefPubMedSuche in Google Scholar