A cost-effectiveness and safety analysis of dual antiplatelet therapy comparing aspirin–clopidogrel to aspirin–ticagrelor in patients with acute coronary syndrome
AbstractBackground: Dual antiplatelet therapy (DAPT) using either an aspirin–clopidogrel (A–C) combination or aspirin–ticagrelor (A–T) combination has become the standard therapy for acute coronary syndrome (ACS). Ticagrelor shows better pharmacokinetic profiles but is more expensive. This study aimed to compare cost-effectiveness and safety profiles of A–C versus A–T in patients with ACS.
Methods: This was a retrospective cohort study of ACS patient at the Cipto Mangunkusumo Hospital between 2014 and 2016. ACS patients treated for the first time with A–T or A–C were included. Occurrence of major adverse cardiovascular events (MACE) within 3, 6, 9, and 12 months were used as effectiveness outcomes, while safety outcomes were measured based on the incidence of adverse drug reactions (major and minor bleeding, dyspnea, and hyperuricemia). Cost-effectiveness analysis was presented as incremental cost-effectiveness ratio (ICER).
Results: Data records obtained from 123 ACS patients treated with A–C and 57 ACS patients treated with A–T were evaluated. Within the first three months, the MACE rate was 15.8% in the A–T group and 31.7% in the A–C group (RR: 0.498, 95% CI: 0.259–0.957, p=0.039). There was no statistically significant difference observed in the number of MACE between groups after 6, 9, and 12 months. The A–T group had a higher incidence of major bleeding (melena) than the A–C group (5.3% vs 1.62%, p=0.681), especially in geriatric patients. Minor bleeding was observed in three patients of the A–C group, but in none of the patients in the A–T group. The cost of ICER was IDR 279,438, indicating the additional cost needed for avoiding MACE within 3 months, if A–T was used.
Conclusion: The aspirin–ticagrelor combination is a clinically superior and cost-effective option for MACE prevention among ACS patients, especially during the first three months of DAPT, with a slight but not significantly higher major bleeding risk when compared to the aspirin–clopidogrel combination.
Finegold JA, Asaria P, Francis DP. Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int J Cardiol. 2013;1658(2):934–45. https://doi.org/10.1016/j.ijcard.2012.10.046
Kementerian Kesehatan RI. Riset Kesehatan Dasar: Riskesdas 2013 [Internet]. Available from:http://www.depkes.go.id/resources/download/general/Hasil%20Riskesdas%202013.pdf
World Health Organization. Cardiovascular diseases (CVDs), [websites], Available from: http://www.who.int/mediacentre/factsheets/fs317/en/
Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST–segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European society of cardiology (ESC). Eur Heart J. 2016;37(3):267–315. https://doi.org/10.1093/eurheartj/ehv320
Parodi G, Marcucci R, Valenti R, Gori AM, Migliorini A, Giusti B, et al. High residual platelet reactivity after clopidogrel loading and long–term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA. 2011;306(11):1215–23. https://doi.org/10.1001/jama.2011.1332
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.
Anonym. Brilinta. Ticagrelor. Azta zeneca, package insert.
Madiyono B, Sastroasmoro S, Budiman I, Purwanto SH. Perkiraan besar sampel. Dalam: Sastroasmoro S, Ismail S, editors. Dasar–dasar metodologi penelitiank linis. Jakarta: SagungSeto; 2014. p352–87. [Indonesian].
Kementrian Kesehatan Republik Indonesia 2015. Pedoman penerapan kajian farmako ekonomi. P:18–41.[Indonesian].
Kim K, Lee TA, Touchette DR, DiDomenico RJ, Ardati AK, Walton SM. Contemporary trends in oral antiplatelet agent use in patients treated with percutaneous coronary intervention for acute coronary syndrome. J Manag Care Spec Pharm. 2017;23(1):57–63. https://doi.org/10.18553/jmcp.2017.23.1.57
Husted S, James S, Becker RC, Horrow J, Katus H, Storey RF, et al. Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes: a substudy from the prospective randomized PLATelet inhibition and patient outcomes (PLATO) trial. Circ Cardiovasc Qual Outcomes. 2012;5(5):680–8.
Siller–Matula JM, Trenk D, Schrör K, Gawaz M, Kristensen SD, Storey RF, et al. Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv. 2013; 6(11):1111–28. https://doi.org/10.1016/j.jcin.2013.06.011
Guha S, Sardar P, Guha P, Roy S, Mookerjee S, Chakrabarti P, et al. Dual antiplatelet drug resistance in patients with acute coronary syndrome. Indian Heart J. 2009;61(1):68–73.
Kumar S, Saran RK, Puri A, Gupta N, Sethi R, Surin WR, et al. Profile and prevalence of clopidogrel resistance in patients of acute coronary syndrome. Indian Heart J. 2007;59(2):152–6.
The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325(25):293–302. https://doi.org/10.1056/NEJM199108013250501
Cattaneo M, Faioni E. Why does ticagrelor induce dyspnea? Thromb Haemost. 2012;108(6):1031–6. https://doi.org/10.1160/TH12-08-0547
Lucenteforte E, Lombardi N, Barchielli A, Torrini M, Mugelli A, Vannacci A. Ticagrelor–related dyspnea in patients with acute coronary syndrome: a three year cohort study. 2015.
Copyright (c) 2018 Nafrialdi Nafrialdi, Novita M. Handini, Instiaty Instiaty, Ika P. Wijaya
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.