EFFECTIVENESS OF TICAGRELOR COMPARED TO CLOPIDOGREL IN REDUCING THE RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH CORONARY HEART DISEASE AFTER PERCUTANEOUS CORONARY INTERVENTION
Objective: Antiplatelet therapy is recommended in patients with coronary heart disease (CHD) who had the percutaneous coronary intervention (PCI) procedure to reduce major adverse cardiovascular events (MACE). There has been a lack of population-based studies that showed the superior effectiveness of ticagrelor over clopidogrel and similar studies have not been conducted in Indonesia yet. The aim of the study was to investigate the effectiveness of ticagrelor compared to clopidogrel in reducing the risk of MACE in patients with CHD after PCI.
Methods: A retrospective cohort study with 1-year follow-up was conducted. 361 patients consisted of 111 patients with ticagrelor exposure and 250 patients with clopidogrel exposure. The primary outcome was MACE, defined as a composite of repeat revascularization, myocardial infarction, or all-cause death. The association between antiplatelet exposure and the MACE was analyzed with Cox proportional hazard regression, adjusted for sex, age, comorbid, PCI procedures and concomitant therapy.
Results: MACE occurred in 22.7% of the subjects. Clopidogrel had a significantly higher risk of MACE compared with ticagrelor (28.8%, vs 9.0%, hazard ratio (HR): 1.96 (95% CI 1.01 to 3.81, p=0.047). There were no significant differences in risk of repeat revascularization (20.40% vs 5.40%, HR: 2.32, 95% CI 0.99 to 5.42, p = 0.05), myocardial infarction (11.60% vs 3.60%, HR: 2.08, 95% CI, 0.73 to 5.93, p = 0.17), and death (1.60% vs 1.80%, HR: 0.77, 95% CI, 0.14 to 4.25, p = 0.77).
Conclusion: Clopidogrel had a higher risk of MACE compared to clopidogrel in patients with CHD after PCI, but there were no significant differences in the risk of repeat revascularization, myocardial infarction, and all-cause death.Â
2. Mendis S, Thygesen K, Kuulasmaa K, Giamsssspaoli S, Mahonen M, Blackett KN, et al. World health organization definition of myocardial infarction: 2008-09 revision. Int J Epidemiol 2011;40:139â€“46.
3. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. ACCF/AHA/SCAI guideline for percutaneous coronary intervention. J Am Coll Cardiol 2011;58:81.
4. Oâ€™Gara PT, Kushner FG, Ascheim DD, Casey DE, Mina K, Lemos JA De, et al. Foundation/American heart association task force on practice guidelines ACCF/AHA guideline 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary a report of the american college of cardiology foundation. Circulation 2013;127:529â€“55.
5. Amsterdam Ea, Wenger NK, Brindis RG, Casey DE, Ganiats TG, Holmes DR, et al. 2014 AHA/ACC guideline for the management of patients with nonâ€“ST-elevation acute coronary syndromes. J Am Coll Cardiol 2014;64:e139â€“228.
6. Wallentin L. P2Y12 inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J 2009;30:1964â€“77.
7. Zhou YH, Wei X, Lu J, Ye XF, Wu MJ, Xu JF, et al. Effects of combined aspirin and clopidogrel therapy on cardiovascular outcomes: a systematic review and meta-analysis. PLoS One 2012;7:e31642.
8. Song PS, Kim DK, Seo GW, Kim KH, Seol SH, Yang JH, et al. Spironolactone lowers the rate of repeat revascularization in acute myocardial infarction patients treated with percutaneous coronary intervention. Am Heart J Mosby Inc 2014;168:346â€“53 e3.
9. Meliga E, Fiorina C, Valgimigli M, Belli R, Gagnor A, Sheiban I, et al. Early angio-guided complete revascularization versus culprit vessel PCI followed by ischemia-guided staged PCI in STEMI patients with multivessel disease. J Interv Cardiol 2011;24:535â€“41.
10. Juwana YB, Wirianta J, Ottervanger JP, Dambrink JHE, Vanâ€™t Hof AWJ, Gosselink TM, et al. Primary coronary intervention for ST-elevation myocardial infarction in Indonesia and the Netherlands: a comparison. Netherlands Hear J 2009;17:418â€“21.
11. Ueshima H, Sekikawa A, Miura K, Turin TC, Takashima N, Kita Y, et al. Cardiovascular disease and risk factors in asia: a selected review. Circulation 2008;118:2702â€“9.
12. Dharma S, Juzar DA, Firdaus I, Soerianata S, Wardeh AJ, Jukema JW. Acute myocardial infarction system of care in the third world. Netherlands Hear J 2012;20:254â€“9.
13. Alhejily WA, Ohman EM. Repeat revascularization after PCI: are we reinventing the wheel or redefining achillesâ€™ heel? Circ Cardiovasc Interv 2012;5:746â€“7.
14. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012;60:1581â€“98.
15. Cannon CP, Brindis RG, Chaitman BR, Cohen DJ, Cross JT, Drozda JP, et al. ACCF/AHA key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes and coronary artery disease: a report of the American college of cardiology foundation/American heart association. Circulation 2013;127:1052â€“89.
16. Leander K, Wiman B, Hallqvist J, Andersson T, Ahlbom A, de Faire U. Primary risk factors influence risk of recurrent myocardial infarction/death from coronary heart disease: results from the stockholm heart epidemiology program (SHEEP). Eur J Cardiovasc Prev Rehabil 2007;14:532â€“7.
17. Picariello C, Lazzeri C, AttanÃ P, Chiostri M, Gensini GF, Valente S. The impact of hypertension on patients with acute coronary syndromes. Int J Hypertens 2011. http://dx.doi.org/ 10.4061/2011/563657
18. Lee MG, Jeong MH, Lee KH, Park KH, Sim DS, Yoon HJ, et al. Prognostic impact of diabetes mellitus and hypertension for the mid-term outcome of patients with acute myocardial infarction who underwent percutaneous coronary intervention. J Cardiol Jpn College Cardiol 2012;60:257â€“63.
19. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: a meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. Be Med J 2009;338:b1665.
20. Kumar S. Dental management of patients on antiplatelet therapy: literature update. Asian J Pharm Clin Res 2016;9:26-31.
21. Schroeder WS, Ghobrial L, Gandhi PJ. Possible mechanisms of drug-induced aspirin and clopidogrel resistance. J Thromb Thrombolysis 2006;22:139â€“50.
22. Bashir S, Poornima R. Pharmacogenetic variations related to clopidogrel resistance and its clinical implications: an issue which remains largely unaddressed. Asian J Pharm Clin Res 2016;9:12-4.
23. Dobesh PP, Oestreich JH. Ticagrelor: pharmacokinetics, pharmacodynamics, clinical efficacy, and safety. Pharmacother J Hum Pharmacol Drug Ther 2014;34:1077â€“90.
24. Tourmousoglou CE, Rokkas CK. Clopidogrel and aspirin in cardiovascular medicine: responders or not--current best available evidence. Cardiovasc Hematol Agents Med Chem 2008;6:312â€“22.
25. Patil TR, Patil S, Patil A, Patil ST. Cardiovascular effects of proton pump inhibitors-a review. Int J Curr Pharm Rev Res 2016;7:198-203.
26. Yasmina A, de Boer A, Klungel OH, Deneer VH. Pharmacogenomics of oral antiplatelet drugs. Pharmacogenomics 2014;15:509â€“28.
27. Husted S, van Giezen JJJ. Ticagrelor: the first reversibly binding oral P2Y 12 receptor antagonist. Cardiovasc Ther 2009;27:259â€“74.
28. Dhillon S. Ticagrelor: a review of its use in adults with acute coronary syndromes. Am J Cardiovasc Drugs 2015;15:51â€“68.
29. Teng R. Ticagrelor: pharmacokinetic, pharmacodynamic and pharmacogenetic profile: an update. Clin Pharmacokinet 2015;54:1125â€“38.
30. Lindholm D, Varenhorst C, Cannon CP, Harrington RA, Himmelmann A, Maya J, et al. Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial. Eur Heart J 2014;35:2083â€“93.
31. Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP, et al. Ticagrelor versus clopidogrel in patients with st-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: a platelet inhibition and patient outcomes (PLATO) trial subgroup analysis. Circulation 2010;122:2131â€“41.
32. Kang HJ, Clare RM, Gao R, Held C, Himmelmann A, James SK, et al. Ticagrelor versus clopidogrel in Asian patients with acute coronary syndrome: a retrospective analysis from the platelet inhibition and patient outcomes (PLATO) trial. Am Heart J 2015;169:899â€“905. e1.
33. Andersson C, MÃ©rie C, JÃ¸rgensen M, Gislason GH, Torp-Pedersen C, Overgaard C, et al. Association of Î²-blocker therapy with risks of adverse cardiovascular events and deaths in patients with ischemic heart disease undergoing noncardiac surgery. JAMA Intern Med 2014;174:336.
34. Al-Gobari M, El Khatib C, Pillon F, Gueyffier F. Beta-blockers for the prevention of sudden cardiac death in heart failure patients: a meta-analysis of randomized controlled trials. BMC Cardiovasc Disord 2013;13:52.