Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Meta-Analysis

Efficacy and Safety of Ticagrelor Compared to Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis

Author(s): Haihong Wu, Xiuying Xiang, Dandan Li, Su Shen* and Xingang Li*

Volume 26, Issue 46, 2020

Page: [5988 - 5997] Pages: 10

DOI: 10.2174/1381612826666200614184007

Price: $65

conference banner
Abstract

Background: The Platelet Inhibition and Patient Outcomes (PLATO) study found that ticagrelor plus aspirin (TA) was more effective than clopidogrel plus aspirin (CA), without an increase in the risk of massive bleeding in patients undergoing percutaneous coronary intervention (PCI). Data from other studies indicate that the conclusion is controversial with the results obtained by PLATO.

Aim: To investigate the efficacy and safety of TA, compared with CA, in patients with acute coronary syndrome (ACS) after PCI.

Methods: A systematic literature search was performed in the MEDLINE, EMBASE, and Cochrane databases to compare the efficacy and safety of CA and TA treatment in patients with ACS after PCI. The endpoints were major adverse cardiac events (MACEs), death, stroke, myocardial infarction (MI), stent thrombosis, and bleeding events. The data analysis was performed using RevMan 5.3 software, and the odds ratios (ORs) and their 95% confidence intervals (CI) were calculated. The standards of reporting were in accordance with the PRISMA guidelines.

Results: 13 studies with a total of 58,062 patients were included in this study with a subgroup analysis of the European/American and Asian populations. In terms of effectiveness for MACEs, the European, American and Asian populations benefitted more from the TA treatment than the CA treatment (European and American populations, OR = 0.82, P = 0.0002; Asian, OR = 0.66, P < 0.0001; total, OR = 0.78, P < 0.0001). In terms of specific effectiveness indicators, such as stroke, MI, and stent thrombosis, the results of TA and CA groups in the European, American, and Asian populations were not consistent. In terms of safety, there was no statistical difference in total bleeding events between TA and CA treatments (OR = 1.19, P = 0.21). However, in the Asian population, the incidence of total bleeding events (OR = 1.52, P = 0.0004) in the TA group was higher than that in the CA group.

Conclusion: The TA treatment in the European and American populations is more beneficial and safer than CA treatment. However, although the Asian population has this benefit, the risk of bleeding is significantly increased as well, and antiplatelet drugs should be chosen carefully.

Keywords: Ticagrelor, clopidogrel, percutaneous coronary intervention, efficacy, safety, bleeding, meta-analysis.

[1]
Joseph P, Leong D, McKee M, et al. Reducing the global burden of cardiovascular disease, part 1: The epidemiology and risk factors. Circ Res 2017; 121(6): 677-94.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.308903] [PMID: 28860318]
[2]
Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the management of patients with non-ST-elevation acute coronary syndromes: A report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol 2014; 64(24): e139-228.
[http://dx.doi.org/10.1016/j.jacc.2014.09.017] [PMID: 25260718]
[3]
Amsterdam EA, Wenger NK, Brindis RG, et al. ACC/AHA task force members; society for cardiovascular angiography and interventions and the society of thoracic surgeons. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130(25): 2354-94.
[http://dx.doi.org/10.1161/CIR.0000000000000133] [PMID: 25249586]
[4]
Dehmer GJ, Blankenship JC, Cilingiroglu M, et al. Society for Cardiovascular Angiography and Interventions; American College of Cardiology; American Heart Association. SCAI/ACC/AHA Expert Consensus Document: 2014 update on percutaneous coronary intervention without on-site surgical backup. Catheter Cardiovasc Interv 2014; 84(2): 169-87.
[http://dx.doi.org/10.1002/ccd.25371] [PMID: 25045090]
[5]
Neumann FJ, Sousa-Uva M, Ahlsson A, et al. [2018 ESC/EACTS Guidelines on myocardial revascularization]. Kardiol Pol 2018; 76(12): 1585-664.
[http://dx.doi.org/10.5603/KP.2018.0228] [PMID: 30566213]
[6]
Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 2006; 27(9): 1038-47.
[http://dx.doi.org/10.1093/eurheartj/ehi754] [PMID: 16476694]
[7]
Storey RF, Husted S, Harrington RA, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol 2007; 50(19): 1852-6.
[http://dx.doi.org/10.1016/j.jacc.2007.07.058] [PMID: 17980251]
[8]
Wallentin L, Becker RC, Budaj A, et al. PLATO Investigators Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361(11): 1045-57.
[http://dx.doi.org/10.1056/NEJMoa0904327] [PMID: 19717846]
[9]
Chen IC, Lee CH, Fang CC, et al. ESTATE Investigators Efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome in Taiwan: A multicenter retrospective pilot study. J Chin Med Assoc 2016; 79(10): 521-30.
[http://dx.doi.org/10.1016/j.jcma.2016.02.010] [PMID: 27339180]
[10]
Tang X, Li R, Jing Q, et al. Assessment of Ticagrelor Versus Clopidogrel Treatment in Patients With ST-elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. J Cardiovasc Pharmacol 2016; 68(2): 115-20.
[http://dx.doi.org/10.1097/FJC.0000000000000390] [PMID: 27010809]
[11]
Jimenez-Britez G, Freixa X, Flores-Umanzor E, et al. Out-of-hospital cardiac arrest and stent thrombosis: Ticagrelor versus clopidogrel in patients with primary percutaneous coronary intervention under mild therapeutic hypothermia. Resuscitation 2017; 114(141-145)
[12]
Goto S, Huang CH, Park SJ, Emanuelsson H, Kimura T. Ticagrelor vs. clopidogrel in Japanese, Korean and Taiwanese patients with acute coronary syndrome -- randomized, double-blind, phase III PHILO study. Circ J 2015; 79(11): 2452-60.
[http://dx.doi.org/10.1253/circj.CJ-15-0112] [PMID: 26376600]
[13]
Kang HJ, Clare RM, Gao R, 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(6): 899-905. e891.
[14]
Park KH, Jeong MH, Ahn Y, et al. Comparison of short-term clinical outcomes between ticagrelor versus clopidogrel in patients with acute myocardial infarction undergoing successful revascularization; from Korea Acute Myocardial Infarction Registry-National Institute of Health. Int J Cardiol 2016; 215: 193-200.
[15]
Wang HY, Li Y, Xu XM, Li J, Han YL. Impact of baseline bleeding risk on efficacy and safety of ticagrelor versus clopidogrel in chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Chin Med J (Engl) 2018; 131(17): 2017-24.
[http://dx.doi.org/10.4103/0366-6999.239306] [PMID: 30127210]
[16]
Kip KE, Hollabaugh K, Marroquin OC, Williams DO. The problem with composite end points in cardiovascular studies: the story of major adverse cardiac events and percutaneous coronary intervention. J Am Coll Cardiol 2008; 51(7): 701-7.
[http://dx.doi.org/10.1016/j.jacc.2007.10.034] [PMID: 18279733]
[17]
Mehran R, Pocock SJ, Nikolsky E, et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol 2010; 55(23): 2556-66.
[http://dx.doi.org/10.1016/j.jacc.2009.09.076] [PMID: 20513595]
[18]
Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123(23): 2736-47.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.009449] [PMID: 21670242]
[19]
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557-60.
[http://dx.doi.org/10.1136/bmj.327.7414.557] [PMID: 12958120]
[20]
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25(9): 603-5.
[http://dx.doi.org/10.1007/s10654-010-9491-z] [PMID: 20652370]
[21]
Nur’amin HW, Dwiprahasto I, Kristin E. 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. Pharmacoepidemiol Drug Saf 2016; 25(S3): 567-7.
[22]
Kim C, Shin DH, Hong SJ, et al. One-year clinical outcomes of ticagrelor compared with clopidogrel after percutaneous coronary intervention in patients with acute myocardial infarction: From Korean Health Insurance Review and Assessment Data. J Cardiol 2019; 73(3): 191-7.
[http://dx.doi.org/10.1016/j.jjcc.2018.08.005] [PMID: 30770037]
[23]
Velders MA, Abtan J, Angiolillo DJ, et al. PLATO investigators Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention. Heart 2016; 102(8): 617-25.
[http://dx.doi.org/10.1136/heartjnl-2015-308963] [PMID: 26848185]
[24]
Steg PG, James S, Harrington RA, et al. PLATO Study Group. 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(21): 2131-41.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.927582] [PMID: 21060072]
[25]
Alexopoulos D, Xanthopoulou I, Deftereos S, et al. Contemporary antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: 1-year outcomes from the GReek AntiPlatElet (GRAPE) Registry. J Thromb Haemost 2016; 14(6): 1146-54.
[http://dx.doi.org/10.1111/jth.13316] [PMID: 26990959]
[26]
Cannon CP, Harrington RA, James S, et al. PLATelet inhibition and patient outcomes investigators. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet 2010; 375(9711): 283-93.
[http://dx.doi.org/10.1016/S0140-6736(09)62191-7] [PMID: 20079528]
[27]
Hee L, Gibbs OJ, Assad JG, et al. Real-world use of ticagrelor versus clopidogrel in percutaneous coronary intervention-treated ST-elevation myocardial infarction patients: A single-center registry study. J Saudi Heart Assoc 2019; 31(4): 151-60.
[http://dx.doi.org/10.1016/j.jsha.2019.05.005] [PMID: 31296977]
[28]
Krishnamurthy A, Keeble C, Anderson M, et al. Real-world comparison of clopidogrel, prasugrel and ticagrelor in patients undergoing primary percutaneous coronary intervention. Open Heart 2019; 6(1)e000951
[http://dx.doi.org/10.1136/openhrt-2018-000951] [PMID: 31328001]
[29]
Gan XD, Wei BZ, Fang D, et al. Efficacy and safety analysis of new P2Y12 inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis. Curr Med Res Opin 2015; 31(12): 2313-23.
[http://dx.doi.org/10.1185/03007995.2015.1098600] [PMID: 26402735]
[30]
Guan W, Lu H, Yang K. Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention: A systematic review and Meta-Analysis (2007-2017). Medicine (Baltimore) 2018; 97(43)e12978
[http://dx.doi.org/10.1097/MD.0000000000012978] [PMID: 30412125]
[31]
Wu B, Lin H, Tobe RG, Zhang L, He B. Ticagrelor versus clopidogrel in East-Asian patients with acute coronary syndromes: a meta-analysis of randomized trials. J Comp Eff Res 2018; 7(3): 281-91.
[http://dx.doi.org/10.2217/cer-2017-0074] [PMID: 29094604]
[32]
Misumida N, Aoi S, Kim SM, Ziada KM, Abdel-Latif A. Ticagrelor versus clopidogrel in East Asian patients with acute coronary syndrome: Systematic review and meta-analysis. Cardiovasc Revasc Med 2018; 19(6): 689-94.
[http://dx.doi.org/10.1016/j.carrev.2018.01.009] [PMID: 29452843]
[33]
Galimzhanov AM, Azizov BS. Ticagrelor for Asian patients with acute coronary syndrome in real-world practice: A systematic review and meta-analysis of observational studies. Indian Heart J 2019; 71(1): 15-24.
[http://dx.doi.org/10.1016/j.ihj.2019.01.003] [PMID: 31000178]
[34]
Wang W, Jiang B, Sun H, et al. Prevalence, incidence, and mortality of stroke in china: results from a nationwide population-based survey of 480687 adults. Circulation 2017; 135(8): 759-71.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.025250] [PMID: 28052979]
[35]
Savi P, Nurden P, Nurden AT, Levy-Toledano S, Herbert JM. Clopidogrel: a review of its mechanism of action. Platelets 1998; 9(3-4): 251-5.
[http://dx.doi.org/10.1080/09537109876799] [PMID: 16793712]
[36]
Nawarskas JJ, Clark SM. Ticagrelor: a novel reversible oral antiplatelet agent. Cardiol Rev 2011; 19(2): 95-100.
[http://dx.doi.org/10.1097/CRD.0b013e3182099d86] [PMID: 21285670]
[37]
Ferreiro JL, Vivas D, De La Hera JM, et al. High and low on-treatment platelet reactivity to P2Y12 inhibitors in a contemporary cohort of acute coronary syndrome patients undergoing percutaneous coronary intervention. Thromb Res 2019; 175: 95-101.
[http://dx.doi.org/10.1016/j.thromres.2019.01.021]
[38]
Husted S, James S, Becker RC, et al. PLATO study group 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.
[http://dx.doi.org/10.1161/CIRCOUTCOMES.111.964395] [PMID: 22991347]
[39]
Chen BL, Zhang W, Li Q, et al. Inhibition of ADP-induced platelet aggregation by clopidogrel is related to CYP2C19 genetic polymorphisms. Clin Exp Pharmacol Physiol 2008; 35(8): 904-8.
[http://dx.doi.org/10.1111/j.1440-1681.2008.04915.x] [PMID: 18346178]
[40]
Scott SA, Sangkuhl K, Stein CM, et al. Clinical pharmacogenetics implementation consortium. Clinical pharmacogenetics implementation consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther 2013; 94(3): 317-23.
[http://dx.doi.org/10.1038/clpt.2013.105] [PMID: 23698643]
[41]
Wu B, Tobe RG, Liu Y, He B. Health economic analysis of antiplatelet therapy for acute coronary syndromes in the context of five eastern asian countries. Clin Drug Investig 2018; 38(7): 621-30.
[http://dx.doi.org/10.1007/s40261-018-0649-x] [PMID: 29713921]
[42]
Schulman S, Kearon C. Subcommittee on control of anticoagulation of the scientific and standardization committee of the international society on thrombosis and haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3(4): 692-4.
[http://dx.doi.org/10.1111/j.1538-7836.2005.01204.x] [PMID: 15842354]
[43]
Bovill EG, Terrin ML, Stump DC, et al. Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. Ann Intern Med 1991; 115(4): 256-65.
[http://dx.doi.org/10.7326/0003-4819-115-4-256] [PMID: 1906692]
[44]
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(20): 2001-15.
[http://dx.doi.org/10.1056/NEJMoa0706482] [PMID: 17982182]
[45]
Sabatine MS, Morrow DA, Giugliano RP, et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation 2005; 111(16): 2042-9.
[http://dx.doi.org/10.1161/01.CIR.0000162477.70955.5F] [PMID: 15824203]
[46]
Moscucci M, Fox KA, Cannon CP, et al. Predictors of major bleeding in acute coronary syndromes: The Global Registry of Acute Coronary Events (GRACE). Eur Heart J 2003; 24(20): 1815-23.
[http://dx.doi.org/10.1016/S0195-668X(03)00485-8] [PMID: 14563340]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy