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Cost Effectiveness of Antiplatelet and Antithrombotic Therapy in the Setting of Acute Coronary Syndrome: Current Perspective and Literature Review

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Abstract

Acute coronary syndromes (ACS) are associated with high rates of morbidity and mortality. The advances of antiplatelet and anticoagulation therapy over several years time have resulted in improved in cardiac outcomes, but with increased health care costs. Multiple cost-effectiveness studies have been performed to evaluate the use of available antiplatelet agents and anticoagulation in the setting of both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Early on, the use of glycoprotein IIb/IIIa receptor inhibitors (GPIs) proved to be economically attractive in the management of ACS; however, the introduction of P2Y12 receptor antagonists limited their use to a bail out agents in complex interventions. Generic clopidogrel is probably still an economically attractive P2Y12 receptor antagonist choice, especially in low-risk ACS, while both ticagrelor and prasugrel present an economically attractive alternative option, especially in high-risk ACS and patients at risk for stent thrombosis. While enoxaparin presents an economically dominant alternative to heparin in NSTE-ACS, its role in STEMI in the contemporary era is unclear. During percutaneous coronary intervention (PCI), bivalirudin monotherapy was shown to be an economically dominant alternative to the combination of heparin and GPI in ACS. However, new studies may suggest that using heparin monotherapy may offer an attractive alternative. The comparative and cost effectiveness of different combinations of antiplatelet and antithrombotic therapy will be the focus of future expected clinical and economic assessments.

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References

  1. Man DL, Zipes DP, Libby P, Bonow R, editors. Braunwald’s Heart Disease: a textbook of cardiovascular disease, 10th edition. Philadelphia: Elsevier; 2014.

    Google Scholar 

  2. Writing Group M, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010;121(7):e46–215 (PubMed PMID: 20019324).

  3. Kolansky DM. Acute coronary syndromes: morbidity, mortality, and pharmacoeconomic burden. Am J Manag Care. 2009;15(2 Suppl):S36–41.

    PubMed  Google Scholar 

  4. Taylor MJ, Scuffham PA, McCollam PL, Newby DE. Acute coronary syndromes in Europe: 1-year costs and outcomes. Curr Med Res Opin. 2007;23(3):495–503.

    Article  PubMed  Google Scholar 

  5. Bagai A, Dangas GD, Stone GW, Granger CB. Reperfusion strategies in acute coronary syndromes. Circ Res. 2014;114(12):1918–28.

    Article  CAS  PubMed  Google Scholar 

  6. Mark DB, Hlatky MA. Medical economics and the assessment of value in cardiovascular medicine: part I. Circulation. 2002;106(4):516–20.

    Article  PubMed  Google Scholar 

  7. Wright JC, Weinstein MC. Gains in life expectancy from medical interventions—standardizing data on outcomes. N Engl J Med. 1998;339(6):380–6.

    Article  CAS  PubMed  Google Scholar 

  8. Gilder SS. London letter. Can Med Assoc J. 1971;104(6):473–81 (PubMed PMID: 20311761. Pubmed Central PMCID: 1930908).

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Simoens S. How to assess the value of medicines? Front Pharmacol. 2010;1:1–9. Art ID 115. (English).

  10. 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(5):437–52.

    Article  PubMed  Google Scholar 

  11. Boersma E. Primary Coronary Angioplasty vs. Thrombolysis G. Does time matter? A pooled analysis of randomized clinical trials comparing primary percutaneous coronary intervention and in-hospital fibrinolysis in acute myocardial infarction patients. Eur Heart J. 2006;27(7):779–88.

    Article  PubMed  Google Scholar 

  12. Huynh T, Perron S, O’Loughlin J, Joseph L, Labrecque M, Tu JV, et al. Comparison of primary percutaneous coronary intervention and fibrinolytic therapy in ST-segment-elevation myocardial infarction: bayesian hierarchical meta-analyses of randomized controlled trials and observational studies. Circulation. 2009;119(24):3101–9.

    Article  PubMed  Google Scholar 

  13. Machecourt J, Bonnefoy E, Vanzetto G, Motreff P, Marliere S, Leizorovicz A, et al. Primary angioplasty is cost-minimizing compared with pre-hospital thrombolysis for patients within 60 min of a percutaneous coronary intervention center: the Comparison of Angioplasty and Pre-hospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) cost-efficacy sub-study. J Am Coll Cardiol. 2005;45(4):515–24.

    Article  PubMed  Google Scholar 

  14. Aasa M, Henriksson M, Dellborg M, Grip L, Herlitz J, Levin LA, et al. Cost and health outcome of primary percutaneous coronary intervention versus thrombolysis in acute ST-segment elevation myocardial infarction-Results of the Swedish Early Decision reperfusion Study (SWEDES) trial. Am Heart J. 2010;160(2):322–8.

    Article  PubMed  Google Scholar 

  15. Grines CL, Schreiber T. Primary percutaneous coronary intervention: the deception of delay. J Am Coll Cardiol. 2013;61(16):1696–7.

    Article  PubMed  Google Scholar 

  16. Wallentin L, Lagerqvist B, Husted S, Kontny F, Stahle E, Swahn E. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC II Investigators. Fast Revascularisation during Instability in Coronary artery disease. Lancet. 2000;356(9223):9–16.

    Article  CAS  PubMed  Google Scholar 

  17. Janzon M, Levin LA, Swahn E. Cost-effectiveness of an invasive strategy in unstable coronary artery disease; results from the FRISC II invasive trial. The Fast Revascularisation during InStability in Coronary artery disease. Eur Heart J. 2002;23(1):31–40.

    Article  CAS  PubMed  Google Scholar 

  18. Cannon CP, Weintraub WS, Demopoulos LA, Vicari R, Frey MJ, Lakkis N, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344(25):1879–87.

    Article  CAS  PubMed  Google Scholar 

  19. Mahoney EM, Jurkovitz CT, Chu H, Becker ER, Culler S, Kosinski AS, et al. Cost and cost-effectiveness of an early invasive vs conservative strategy for the treatment of unstable angina and non-ST-segment elevation myocardial infarction. JAMA. 2002;288(15):1851–8.

    Article  PubMed  Google Scholar 

  20. The ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2(8607):349–60.

    Google Scholar 

  21. The RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis) Invistigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis. Circulation. 1997;96(5):1445–53.

    Article  Google Scholar 

  22. Weintraub WS, Culler S, Boccuzzi SJ, Cook JR, Kosinski AS, Cohen DJ, et al. Economic impact of GPIIB/IIIA blockade after high-risk angioplasty: results from the RESTORE trial. Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis. J Am Coll Cardiol. 1999;34(4):1061–6.

    Article  CAS  PubMed  Google Scholar 

  23. The PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. The PURSUIT Trial Investigators. Platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy. N Engl J Med. 1998;339(7):436–43.

    Article  Google Scholar 

  24. Mark DB, Harrington RA, Lincoff AM, Califf RM, Nelson CL, Tsiatis AA, et al. Cost-effectiveness of platelet glycoprotein IIb/IIIa inhibition with eptifibatide in patients with non-ST-elevation acute coronary syndromes. Circulation. 2000;101(4):366–71.

    Article  CAS  PubMed  Google Scholar 

  25. Rupprecht HJ, Darius H, Borkowski U, Voigtlander T, Nowak B, Genth S, et al. Comparison of antiplatelet effects of aspirin, ticlopidine, or their combination after stent implantation. Circulation. 1998;97(11):1046–52.

    Article  CAS  PubMed  Google Scholar 

  26. Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;358(9281):527–33.

    Article  CAS  PubMed  Google Scholar 

  27. Mahoney EM, Mehta S, Yuan Y, Jackson J, Chen R, Gabriel S, et al. Long-term cost-effectiveness of early and sustained clopidogrel therapy for up to 1 year in patients undergoing percutaneous coronary intervention after presenting with acute coronary syndromes without ST-segment elevation. Am Heart J. 2006;151(1):219–27.

    Article  CAS  PubMed  Google Scholar 

  28. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–15.

    Article  CAS  PubMed  Google Scholar 

  29. Mahoney EM, Wang K, Arnold SV, Proskorovsky I, Wiviott S, Antman E, 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(1):71–9.

    Article  PubMed  Google Scholar 

  30. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–57.

    Article  CAS  PubMed  Google Scholar 

  31. Nikolic E, Janzon M, Hauch O, Wallentin L, Henriksson M, Group PHES. Cost-effectiveness of treating acute coronary syndrome patients with ticagrelor for 12 months: results from the PLATO study. Eur Heart J. 2013;34(3):220–8.

    Article  Google Scholar 

  32. Theroux P, Ouimet H, McCans J, Latour JG, Joly P, Levy G, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319(17):1105–11.

    Article  CAS  PubMed  Google Scholar 

  33. Oler A, Whooley MA, Oler J, Grady D. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis. JAMA. 1996;276(10):811–5.

    Article  CAS  PubMed  Google Scholar 

  34. Cohen M, Demers C, Gurfinkel EP, Turpie AG, Fromell GJ, Goodman S, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997;337(7):447–52.

    Article  CAS  PubMed  Google Scholar 

  35. Mark DB, Cowper PA, Berkowitz SD, Davidson-Ray L, DeLong ER, Turpie AG, et al. Economic assessment of low-molecular-weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patients: results from the ESSENCE randomized trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events [unstable angina or non-Q-wave myocardial infarction]. Circulation. 1998;97(17):1702–7.

    Article  CAS  PubMed  Google Scholar 

  36. Antman EM, Morrow DA, McCabe CH, Murphy SA, Ruda M, Sadowski Z, et al. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med. 2006;354(14):1477–88.

    Article  CAS  PubMed  Google Scholar 

  37. Marcoff L, Zhang Z, Zhang W, Ewen E, Jurkovitz C, Leguet P, et al. Cost effectiveness of enoxaparin in acute ST-segment elevation myocardial infarction: the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) study. J Am Coll Cardiol. 2009;54(14):1271–9.

    Article  PubMed  Google Scholar 

  38. Fifth Organization to Assess Strategies in Acute Ischemic Syndromes I, Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006;354(14):1464–76 (PubMed PMID: 16537663).

  39. Sculpher MJ, Lozano-Ortega G, Sambrook J, Palmer S, Ormanidhi O, Bakhai A, et al. Fondaparinux versus Enoxaparin in non-ST-elevation acute coronary syndromes: short-term cost and long-term cost-effectiveness using data from the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators (OASIS-5) trial. Am Heart J. 2009;157(5):845–52.

    Article  CAS  PubMed  Google Scholar 

  40. Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, et al. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA. 2006;295(13):1519–30.

    Article  CAS  PubMed  Google Scholar 

  41. Stone GW, White HD, Ohman EM, Bertrand ME, Lincoff AM, McLaurin BT, et al. Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Trial. Lancet. 2007;369(9565):907–19.

    Article  CAS  PubMed  Google Scholar 

  42. Pinto DS, Stone GW, Shi C, Dunn ES, Reynolds MR, York M, et al. Economic evaluation of bivalirudin with or without glycoprotein IIb/IIIa inhibition versus heparin with routine glycoprotein IIb/IIIa inhibition for early invasive management of acute coronary syndromes. J Am Coll Cardiol. 2008;52(22):1758–68.

    Article  CAS  PubMed  Google Scholar 

  43. Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med. 2008;358(21):2218–30.

    Article  CAS  PubMed  Google Scholar 

  44. Schwenkglenks M, Toward TJ, Plent S, Szucs TD, Blackman DJ, Baumbach A. Cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor in the treatment of acute ST-segment elevation myocardial infarction. Heart. 2012;98(7):544–51.

    Article  CAS  PubMed  Google Scholar 

  45. Shahzad A, Kemp I, Mars C, Wilson K, Roome C, Cooper R, et al. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet. 2014;384(9957):1849–58.

    Article  CAS  PubMed  Google Scholar 

  46. Han Y, Guo J, Zheng Y, Zang H, Su X, Wang Y, Chen S, et al. Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial. JAMA. 2015;313(13):1336–46.

    Article  CAS  PubMed  Google Scholar 

  47. Cavender MA, Sabatine MS. Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials. Lancet. 2014;384(9943):599–606.

    Article  CAS  PubMed  Google Scholar 

  48. Cassese S, Byrne RA, Laugwitz KL, Schunkert H, Berger PB, Kastrati A. Bivalirudin versus heparin in patients treated with percutaneous coronary intervention: a meta-analysis of randomised trials. EuroIntervention. 2014. doi:10.4244/EIJY14M08_01.

    PubMed  Google Scholar 

  49. Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371(23):2155–66.

    Article  PubMed Central  PubMed  Google Scholar 

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Funding source

The time spent by Dr. Weintraub overseeing and guiding Dr. Fanari writing the manuscript was funded by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number U54-GM104941 (PI: Binder-Macleod).

Conflict of interest disclosure statements

Dr. Weintraub is a consultant to, and has had previous grant funding from, Sanofi-Aventis, AstraZeneca, Lilly and Daiichi- Sankyo. Drs. Fanari and Weiss report no potential conflicts of interest that might be relevant to the contents of this review.

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  1. Section of Cardiology, Christiana Care Health System, 4755 Ogletown-Stanton Rd., Newark, DE, 19718, USA

    Zaher Fanari, Sandra Weiss & William S. Weintraub

  2. Value Institute, Christiana Care Health System, Newark, DE, USA

    William S. Weintraub

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  1. Zaher Fanari
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  2. Sandra Weiss
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Correspondence to Zaher Fanari.

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Fanari, Z., Weiss, S. & Weintraub, W.S. Cost Effectiveness of Antiplatelet and Antithrombotic Therapy in the Setting of Acute Coronary Syndrome: Current Perspective and Literature Review. Am J Cardiovasc Drugs 15, 415–427 (2015). https://doi.org/10.1007/s40256-015-0131-6

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