A Meta-Analysis of Randomized Controlled Trials Appraising the Efficacy and Safety of Cilostazol after Coronary Artery Stent ImplantationJang J.-S.a · Jin H.-Y.a · Seo J.-S.a · Yang T.-H.a · Kim D.-K.a · Kim D.-S.a · Kim D.-K.b · Seol S.-H.b · Kim D.-I.b · Cho K.-I.c · Kim B.-H.d · Park Y.H.e · Je H.-G.e · Jeong Y.-H.f · Kim W.-J.g · Lee J.-Y.g · Lee S.-W.g
aBusan Paik Hospital, University of Inje College of Medicine, bHaeundae Paik Hospital, cMaryknoll Medical Center, dPusan National University Hospital, Busan, eResearch Institute for Covergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, fGyeongsang National University Hospital, Jinju, and gAsan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Article / Publication Details
Objectives: To evaluate the impact of cilostazol on the angiographic and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) with stents and treated with aspirin and thienopyridine. Methods: A total of 11 randomized controlled trials including 8,525 patients comparing triple antiplatelet therapy (aspirin, thienopyridine and cilostazol) with standard dual antiplatelet therapy were included in the analysis. The primary end points were in-segment late loss and angiographic restenosis at angiographic follow-up. Secondary end points included mortality, stent thrombosis, target lesion revascularization (TLR) and major adverse cardiac events (MACE). Results: Triple antiplatelet therapy was associated with a significant reduction in late loss [weighted mean difference 0.14, 95% confidence interval (CI) 0.08–0.20; p < 0.001] and angiographic restenosis [odds ratio (OR) 0.58, 95% CI 0.48–0.71; p < 0.001]. Addition of cilostazol to dual antiplatelet therapy was associated with a significant reduction in TLR (OR 0.56, 95% CI 0.41–0.77; p < 0.001) and MACE (OR 0.72, 95% CI 0.60–0.86; p < 0.001) with no differences in mortality (p = 0.29), stent thrombosis (p = 0.60) or bleeding episodes (p = 0.77). Conclusions: Cilostazol in addition to dual antiplatelet therapy appears to be effective in reducing the risk of restenosis and repeat revascularization after PCI without any significant benefits for mortality or stent thrombosis.
© 2012 S. Karger AG, Basel
- Solinas E, Dangas G, Kirtane AJ, Lansky AJ, Franklin-Bond T, Boland P, Syros G, Kim YH, Gupta A, Mintz G, Fahy M, Collins M, Kodali S, Stone GW, Moses JW, Leon MB, Mehran R: Angiographic patterns of drug-eluting stent restenosis and one-year outcomes after treatment with repeated percutaneous coronary intervention. Am J Cardiol 2008;102:311–315.
- Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C, Kukreja N, Juni P, Sianos G, Hellige G, van Domburg RT, Hess OM, Boersma E, Meier B, Windecker S, Serruys PW: Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet 2007;369:667–678.
- Mauri L, Hsieh WH, Massaro JM, Ho KK, D’Agostino R, Cutlip DE: Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 2007;356:1020–1029.
- Regensteiner JG, Stewart KJ: Established and evolving medical therapies for claudication in patients with peripheral arterial disease. Nat Clin Pract Cardiovasc Med 2006;3:604–610.
- Douglas JS Jr, Holmes DR Jr, Kereiakes DJ, Grines CL, Block E, Ghazzal ZM, Morris DC, Liberman H, Parker K, Jurkovitz C, Murrah N, Foster J, Hyde P, Mancini GB, Weintraub WS; Cilostazol for Restenosis Trial (CREST) Investigators: Coronary stent restenosis in patients treated with cilostazol. Circulation 2005;112:2826–2832.
- Lee SW, Park SW, Kim YH, Yun SC, Park DW, Lee CW, Hong MK, Kim HS, Ko JK, Park JH, Lee JH, Choi SW, Seong IW, Cho YH, Lee NH, Kim JH, Chun KJ, Park SJ: 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.
- Pan X, Arauz E, Krzanowski JJ, Fitzpatrick DF, Polson JB: Synergistic interactions between selective pharmacological inhibitors of phosphodiesterase isozyme families PDE III and PDE IV to attenuate proliferation of rat vascular smooth muscle cells. Biochem Pharmacol 1994;48:827–835.
- Kubota Y, Kichikawa K, Uchida H, Maeda M, Nishimine K, Makutani S, Sakaguchi S, Yoshioka T, Ohishi H, Kimura Y: Pharmacologic treatment of intimal hyperplasia after metallic stent placement in the peripheral arteries. An experimental study. Invest Radiol 1995;30:532–537.
- Kunishima T, Musha H, Eto F, Iwasaki T, Nagashima J, Masui Y, So T, Nakamura T, Oohama N, Murayama M: A randomized trial of aspirin versus cilostazol therapy after successful coronary stent implantation. Clin Ther 1997;19:1058–1066.
- Park SW, Lee CW, Kim HS, Lee HJ, Park HK, Hong MK, Kim JJ, Park SJ: Comparison of cilostazol versus ticlopidine therapy after stent implantation. Am J Cardiol 1999;84:511–514.
- Kamishirado H, Inoue T, Mizoguchi K, Uchida T, Nakata T, Sakuma M, Takayanagi K, Morooka S: Randomized comparison of cilostazol versus ticlopidine hydrochloride for antiplatelet therapy after coronary stent implantation for prevention of late restenosis. Am Heart J 2002;144:303–308.
- Ge J, Han Y, Jiang H, Sun B, Chen J, Zhang S, Du Z; RACTS (Randomized Prospective Antiplatelet Trial of Cilostazol Versus Ticlopidine in Patients Undergoing Coronary Stenting) Trial Investigators: RACTS: a prospective randomized antiplatelet trial of cilostazol versus ticlopidine in patients undergoing coronary stenting: long-term clinical and angiographic outcome. J Cardiovasc Pharmacol 2005;46:162–166.
- Tanabe Y, Ito E, Nakagawa I, Suzuki K: Effect of cilostazol on restenosis after coronary angioplasty and stenting in comparison to conventional coronary artery stenting with ticlopidine. Int J Cardiol 2001;78:285–291.
- Takagi H, Umemoto T: A meta-analysis of randomized trials of triple versus dual antiplatelet therapy after stent-based percutaneous coronary intervention. Int J Cardiol 2011;150:228–230.
- Laskey WK, Yancy CW, Maisel WH: Thrombosis in coronary drug-eluting stents: report from the meeting of the Circulatory System Medical Devices Advisory Panel of the Food and Drug Administration Center for Devices and Radiologic Health, December 7–8, 2006. Circulation 2007;115:2352–2357.
- Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.
- Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634.
- Duval S, Tweedie R: Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000;56:455–463.
- Chen YD, Lu YL, Jin ZN, Yuan F, Lu SZ: A prospective randomized antiplatelet trial of cilostazol versus clopidogrel in patients with bare metal stent. Chin Med J (Engl) 2006;119:360–366.
- Min PK, Jung JH, Ko YG, Choi D, Jang Y, Shim WH: Effect of cilostazol on in-stent neointimal hyperplasia after coronary artery stenting: a quantative coronary angiography and volumetric intravascular ultrasound study. Circ J 2007;71:1685–1690.
- Lee SW, Park SW, Kim YH, Yun SC, Park DW, Lee CW, Hong MK, Kim HS, Ko JK, Park JH, Lee JH, Choi SW, Seong IW, Cho YH, Lee NH, Kim JH, Chun KJ, Park SJ; DECLARE-Long Study Investigators: Comparison of triple versus dual antiplatelet therapy after drug-eluting stent implantation (from the DECLARE-Long trial). Am J Cardiol 2007;100:1103–1108.
- Ahn Y, Jeong MH, Jeong JW, Kim KH, Ahn TH, Kang WC, Park CG, Kim JH, Chae IH, Nam CW, Hur SH, Bae JH, Kim KY, Oh SK: Randomized comparison of cilostazol vs clopidogrel after drug-eluting stenting in diabetic patients – clilostazol for diabetic patients in drug-eluting stent (CIDES) trial. Circ J 2008;72:35–39.
Kim DH, Kim JY, Moon SW, Jung JH, Yang HS, Cho JH, Jeong MH: Effects of long-term triple anti-platelet therapy with low-dose cilostazol after drug-eluting stent implantation. Korean J Med 2008;74:368–375.
- Han Y, Li Y, Wang S, Jing Q, Wang Z, Wang D, Shu Q, Tang X: Cilostazol in addition to aspirin and clopidogrel improves long-term outcomes after percutaneous coronary intervention in patients with acute coronary syndromes: a randomized, controlled study. Am Heart J 2009;157:733–739.
- Suh JW, Lee SP, Park KW, Lee HY, Kang HJ, Koo BK, Cho YS, Youn TJ, Chae IH, Choi DJ, Rha SW, Bae JH, Kwon TG, Bae JW, Cho MC, Kim HS: Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON-T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial. J Am Coll Cardiol 2011;57:280–289.
- Lee SW, Park SW, Kim YH, Yun SC, Park DW, Lee CW, Kang SJ, Park SJ, Lee JH, Choi SW, Seong IW, Lee NH, Cho YH, Shin WY, Lee SJ, Lee SW, Hyon MS, Bang DW, Choi YJ, Kim HS, Lee BK, Lee K, Park HK, Park CB, Lee SG, Kim MK, Park KH, Park WJ; DECLARE-LONG II Study Investigators: A randomized, double-blind, multicenter comparison study of triple antiplatelet therapy with dual antiplatelet therapy to reduce restenosis after drug-eluting stent implantation in long coronary lesions: results from the DECLARE-LONG II (drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions) trial. J Am Coll Cardiol 2011;57:1264–1270.
Park KW, Kim HS, Kang HJ, Koo BK, Chae IH: Randomized comparison of adding cilostazol versus doubling the dose of clopidogrel after receiving percutaneous coronary intervention: the HOST-ASSURE randomized trial. Presented as a late-breaking clinical trial at the American College of Cardiology 61st Annual Scientific Session, Chicago, Ill., March 2012.
- Morishita R: A scientific rationale for the CREST trial results: evidence for the mechanism of action of cilostazol in restenosis. Atheroscler Suppl 2005;6:41–46.
- Hashiguchi M, Ohno K, Nakazawa R, Kishino S, Mochizuki M, Shiga T: Comparison of cilostazol and ticlopidine for one-month effectiveness and safety after elective coronary stenting. Cardiovasc Drugs Ther 2004;18:211–217.
- Lee SW, Park SW, Hong MK, Lee CW, Kim YH, Park JH, Kang SJ, Han KH, Kim JJ, Park SJ: Comparison of cilostazol and clopidogrel after successful coronary stenting. Am J Cardiol 2005;95:859–862.
- Biondi-Zoccai GG, Lotrionte M, Anselmino M, Moretti C, Agostoni P, Testa L, Abbate A, Cosgrave J, Laudito A, Trevi GP, Sheiban I: Systematic review and meta-analysis of randomized clinical trials appraising the impact of cilostazol after percutaneous coronary intervention. Am Heart J 2008;155:1081–1089.
- Zhang Z, Foster JK, Kolm P, Jurkovitz CT, Parker KM, Murrah NV, Anderson GT, Douglas JS Jr, Weintraub WS: Reduced 6-month resource use and costs associated with cilostazol in patients after successful coronary stent implantation: results from the cilostazol for RESTenosis (CREST) trial. Am Heart J 2006;152:770–776.
- Kim JS, Lee KS, Kim YI, Tamai Y, Nakahata R, Takami H: A randomized crossover comparative study of aspirin, cilostazol and clopidogrel in normal controls: analysis with quantitative bleeding time and platelet aggregation test. J Clin Neurosci 2004;11:600–602.
- Comerota AJ: Effect on platelet function of cilostazol, clopidogrel, and aspirin, each alone or in combination. Atheroscler Suppl 2005;6:13–19.
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