Thromb Haemost 2014; 111(02): 290-299
DOI: 10.1160/TH13-08-0679
Platelets and Blood Cells
Schattauer GmbH

A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients

Niels Straub*
1   Institute of Market Research, Statistics and Prognosis (IMSP), Munich, Germany
,
Andreas Beivers*
2   Fresenius University of Applied Sciences Munich, Germany
,
Ekaterina Lenk
3   Verum Diagnostica GmbH, Roche Professional Diagnostics, Munich, Germany
,
Daniel Aradi#
4   Department of Cardiology, Heart Center, Balatonfüred, Hungary
,
Dirk Sibbing#
5   Department of Cardiology, Ludwig-Maximilians University, Munich, Germany
› Author Affiliations
Further Information

Publication History

Received: 19 August 2013

Accepted after major revision: 27 September 2013

Publication Date:
27 November 2017 (online)

Summary

Although some observational studies reported that the measured level of P2Y12-inhibition is predictive for thrombotic events, the clinical and economic benefit of incorporating PFT to personalize P2Y12-receptor directed antiplatelet treatment is unknown. Here, we assessed the clinical impact and cost-effectiveness of selecting P2Y12-inhibitors based on platelet function testing (PFT) in acute coronary syndrome (ACS) patients undergoing PCI. A decision model was developed to analyse the health economic effects of different strategies. PFT-guided treatment was compared with the three options of general clopidogrel, prasugrel or ticagrelor treatment. In the PFT arm, low responders to clopidogrel received prasugrel, while normal responders carried on with clopidogrel. The associated endpoints in the model were cardiovascular death, stent thrombosis and major bleeding. With a simulated cohort of 10,000 patients treated for one year, there were 93 less events in the PFT arm compared to general clopidogrel. In prasugrel and ticagrelor arms, 110 and 86 events were prevented compared to clopidogrel treatment, respectively. The total expected costs (including event costs, drug costs and PFT costs) for generic clopidogrel therapy were US$ 1,059/patient. In the PFT arm, total costs were US$ 1,494, while in the prasugrel and ticagrelor branches they were US$ 3,102 and US$ 3,771, respectively. The incrementalcost- effectiveness-ratio (ICER) was US$ 46,770 for PFT-guided therapy, US$ 185,783 for prasugrel and US$ 315,360 for ticagrelor. In this model-based analysis, a PFT-guided therapy may have fewer adverse outcomes than general treatment with clopidogrel and may be more cost-effective than prasugrel or ticagrelor treatment in ACS patients undergoing PCI.

* Both authors are first authors of this manuscript.


# Both authors are senior authors of this manuscript.


 
  • References

  • 1 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: 2999-3054.
  • 2 Steg PG, James SK, Atar D. et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J 2012; 33: 2569-2619.
  • 3 Wallentin L, Becker RC, Budaj A. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.
  • 4 Wiviott SD, Braunwald E, McCabe CH. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
  • 5 Trenk D, Stone GW, Gawaz M. et al. A Randomized Trial of Prasugrel Versus Clopidogrel in Patients With High Platelet Reactivity on Clopidogrel After Elective Percutaneous Coronary Intervention With Implantation of Drug-Eluting Stents: Results of the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) Study. J Am Coll Cardiol 2012; 59: 2159-2164.
  • 6 Price MJ, Berger PB, Teirstein PS. et al. 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.
  • 7 Collet JP, Cuisset T, Range G. et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367: 2100-2109.
  • 8 Stone GW ADAPT-DES: A Large-Scale, Prospective, Multicenter Registry Examining the Relationship of Platelet Responsiveness to Stent Thrombosis After DES Implantation. Transcatheter Cardiovascular Therapeutics 2011, San Francisco, November 9, 2011.
  • 9 Sibbing D, Steinhubl SR, Schulz S. et al. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 2010; 56: 317-318.
  • 10 Bonello L, Tantry US, Marcucci R. et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56: 919-933.
  • 11 Cutlip DE, Windecker S, Mehran R. et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007; 115: 2344-2351.
  • 12 TIMI bleeding definition defined according to http://www.timi.org?page_id=76; Accessed on March 1, 2013.
  • 13 Cannon CP, Harrington RA, James S. et al. Comparison of ticagrelor with clopi-dogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet 2010; 375: 283-293.
  • 14 Schulz S, Sibbing D, Braun S. et al. Platelet response to clopidogrel and restenosis in patients treated predominantly with drug-eluting stents. Am Heart J 2010; 160: 355-361.
  • 15 Aradi D, Pinter T, Magayari B. Optimizing P2Y12-Receptor Inhibition in Acute Coronary Syndrome Patients after PCI Using Platelet Function Testing: Impact of Prasugrel versus High-Dose Clopidogrel. J Am Coll Cardiol 2013; 61 (Suppl A) A477.
  • 16 Siller-Matula JM, Francesconi M, Dechant C. et al. Personalized antiplatelet treatment after percutaneous coronary intervention: The MADONNA study. Int J Cardiol. 2012 Epub ahead of print.
  • 17 Hazarbasanov D, Velchev V, Finkov B. et al. Tailoring clopidogrel dose according to multiple electrode aggregometry decreases the rate of ischemic complications after percutaneous coronary intervention. J Thromb Thrombolysis 2012; 34: 85-90.
  • 18 United States Department of Labor, Bureau of labor statistics. Available at: http://www.bls.gov/cpi/tables.htm. Accessed on March 1, 2013.
  • 19 GoodRx.. Available at: www.goodrx.com Accessed on March 1, 2013.
  • 20 HealthWarehouse.. Available at: www.healthwarehouse.com Accessed on March 1, 2013.
  • 21 Rote Liste.. Available at: www.rote-liste.de Accessed on March 1, 2013.
  • 22 Schleinitz MD, Heidenreich PA. A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone. Ann Intern Med 2005; 142: 251-259.
  • 23 Reynolds MR, Rinaldi MJ, Pinto DS. et al. Current clinical characteristics and economic impact of subacute stent thrombosis. J Invasive Cardiol 2002; 14: 364-368.
  • 24 Ewen EF, Zhao L, Kolm P. et al. Determining the in-hospital cost of bleeding in patients undergoing percutaneous coronary intervention. J Interv Cardiol 2009; 22: 266-273.
  • 25 Wright RS, Anderson JL, Adams CD. et al. 2011 ACCF/AHA focused update of the Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2011; 57: 1920-1959.
  • 26 Coleman CI, Limone BL. Cost-Effectiveness of Universal and Platelet Reactivity Assay-Driven Antiplatelet Therapy in Acute Coronary Syndrome. Am J Cardiol. 2013 Epub ahead of print.
  • 27 Mahoney EM, Wang K, Arnold SV. et al. Cost-effectiveness of prasugrel versus clopidogrel in patients with acute coronary syndromes and planned percutaneous coronary intervention: results from the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with Prasugrel-Thrombolysis in Myocardial Infarction TRITON-TIMI 38. Circulation 2010; 121: 71-79.
  • 28 Nikolic E, Janzon M, Hauch O. et al. Cost-effectiveness of treating acute coronary syndrome patients with ticagrelor for 12 months: results from the PLATO study. Eur Heart J 2013; 34: 220-228.
  • 29 Floyd JS, Serebruany VL. Prasugrel as a potential cancer promoter: review of the unpublished data. Arch Intern Med 2010; 170: 1078-1080.