
The Risk of Bleeding in Triple Antiplatelet Therapy: Cilostazol Added to Aspirin and Clopidogrel for Coronary Artery Disease Patients Who Underwent Percutaneous Coronary Intervention: A Meta-Analysis Study of Randomized Controlled Trials
Abstract
BACKGROUND: A novel cilostazol-based triple antiplatelet therapy (TAT) was shown in a trial to have a lower restenosis rate than the usual clopidogrel and aspirin dual antiplatelet therapy (DAPT) among patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention. However, TAT may also be associated with an increased risk of bleeding. A systematic review would show further evidence regarding the risk of bleeding among TAT-treated patients.
MAIN OBJECTIVE: To determine the risk of bleeding with TAT composed of cilostazol, aspirin and clopidogrel for CAD patients who underwent percutaneous coronary intervention.
METHODS: This systematic review included randomized controlled trials (RCT) published from 2005 to 2014. Only one study was blinded. These studies compared the risk of major bleeding between DAPT and TAT. Meta-analysis of this outcome was conducted using Review Manager (RevMan) Version 5.3 2014.
RESULTS: The overall relative risk (RR) of major bleeding in TAT patients was 1.23 (CI 95% 0.90, 1.67; z=1.30, p=0.19). The heterogeneity of results of the seven studies was not statistically significant (p=0.88; I2=0%). When isolating those studies with favorable outcome with TAT, the risk of bleeding demonstrated in five studies was also not statistically significant (p=0.11; I2=0%). Sensitivity analysis on two studies with wider deviation and slightly lower rates of bleeding showed no significant influence on the risk of bleeding (RR 0.78; CI 0.29, 2.09; p=0.63; I2=0%).
CONCLUSION: Compared with DAPT, the trend towards increased major bleeding in cilostazol -based TAT did not reach statistical significance.
- Tamhane U, Meier P, Chetcuti S, et al. Efficacy of cilostazol in reducing restenosis in patients undergoing contemporary stent based PCI: a meta-analysis of randomised controlled trials. Euro Intervention 2009;5:384-393.
- Youn YJ, Lee JW, Ahn SG, Lee SH, Choi H, et al. Multicenter randomized trial of 3-month cilostazol use in addition to dual antiplatelet therapy after biolimus-eluting stent implantation for long or multivessel coronary artery disease. Am Heart J 2014;167:241-248.
- Gao W, Zhang Q, Ge H, Guo Y, Zhou Z. Efficacy and safety of triple antiplatelet therapy in obese patients undergoing stent implantation. Angiology 2013;64:554-558.
- Lee SW, Park SW, Kim YH, Yun SC, Park DW, et al. Comparison of triple versus dual antiplatelet therapy after drug-eluting stent implantation (from the DECLARE-Long trial). Am J Cardiol 2007;100:1103-1108.
- Lee SW, Park SW, Kim YH, Yun SC, Park DW, et al. Drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with diabetes mellitus the DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients). J Am Coll Cardiol 2008;51:1181-1187.
- Lee SW, Lee JY, Ahn JM, Park DW, Han S, et al. Comparison of dual versus triple antiplatelet therapy after drug-eluting stent according to stent length (from the pooled analysis of DECLARE trials). Am J Cardiol 2013;112:1738-1744.
- Han YL, Su QF, Li Y, Wang SL, et al. Short-term outcomes of triple antiplatelet therapy after percutaneous coronary intervention. Zhonghua Yi Xue Za Zhi 2006 Apr 25;86:1093-1096.
- Lee SW, Park SW, Hong MK, et al. Triple versus dual antiplatelet therapy after coronary stenting: impact on stent thrombosis. J Am Coll Cardiol 2005;46:1833-1837.
- Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006;354:1706-1717.
- De Berardis G, Lucisano G, D’Ettorre A, Pellegrini F, Lepore V, Tognoni G, Nicolucci A. Association of aspirin use with major bleeding in patients with and without diabetes. JAMA 2012 Jun 6;307(21):2286-94.
- Mehta SR, Yusuf S; Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Study Investigators. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial programme; rationale, design and baseline characteristics including a meta-analysis of the effects of thienopyridines in vascular disease. Eur Heart J. 2000 Dec;21(24):2033-41.
- Rizzo M, Corrado E, Patti AM, Rini GB, Mikhailidis DP. Cilostazol and atherogenic dyslipidemia: a clinically relevant effect? Expert Opin Pharmacother 2011;12:647-655.
- Ahn CM, Hong SJ, Park JH, Kim JS, Lim DS. Cilostazol reduces the progression of carotid intima-media thickness without increasing the risk of bleeding in patients with acute coronary syndrome during a 2-year follow-up. Heart Vessels 2011;26:502-510.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0
International License, which permits use, share — copy and redistribute the material in any medium or format,
adapt — remix, transform, and build upon the material, as long as you give appropriate credit,
provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner,
but not in any way that suggests the licensor endorses you or your use. You may not use the material for
commercial purposes. If you remix, transform, or build upon the material, you must distribute your
contributions under the same license as the original. You may not apply legal terms or technological
measures that legally restrict others from doing anything the license permits. The images or other
third party material in this article are included in the article’s Creative Commons license, unless indicated
otherwise in a credit line to the material. If material is not included in the article’s Creative Commons
license and your intended use is not permitted by statutory regulation or exceeds the permitted use,
you will need to obtain permission directly from the copyright holder. To view a copy of this license,
visit https://creativecommons.org/licenses/by-nc-sa/4.0/.