Abstract
Several clinical studies have reported the use of cilostazol in addition to aspirin and thienopyridine (triple antiplatelet therapy, TAPT) after percutaneous coronary intervention (PCI) decreases clinical events. However, the efficacy and safety of TAPT have not been fully evaluated in Japan. The prospectively collected data from 12824 Japanese patients received PCI as part of the j-Cypher Registry were analyzed. We selected 10356 patients who exclusively received implantation of sirolimus-eluting stents (SES), and compared the data from 10128 patients who received dual antiplatelet therapy (aspirin + thienopyridine, DAPT) with 228 patients who received TAPT at the time of discharge. Patients who received TAPT had more comorbidities, such as peripheral vascular disease, renal failure with hemodialysis or insulin dependent diabetes mellitus, and more patients received stenting for the left main trunk. The cardiovascular event rates at 3 years after PCI in the TAPT group were not significantly different from DAPT group, even after adjusted risks for cardiovascular events; all-cause death (7.8 vs. 6.7 %, log-rank p = 0.44, adjusted Hazard Ratio [HR] 0.88: 95 % confidence interval [CI] 0.52–1.38, p = 0.61), myocardial infarction (1.7 vs. 2.4 %, log-rank p = 0.49 and HR 0.71: 95 % CI 0.20–1.57, p = 0.40), target legion revascularization (12.7 vs. 9.9 %, log-rank p = 0.11 and HR 1.05: 95 % CI 0.71–1.50, p = 0.91) and stroke (3.9 vs. 3.2 %, log-rank p = 0.52 and HR 1.09: 95 % CI 0.52–2.00, p = 0.80). In conclusion, TAPT after SES implantation was associated with similar long-term clinical outcomes as DAPT in Japanese real-world clinical practice, although we did not evaluate the bleeding outcome.
Similar content being viewed by others
References
Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996;334:1084–9.
Douglas JS Jr, Holmes DR Jr, Kereiakes DJ, Grines CL, Block E, Ghazzal ZM, et al. Coronary stent restenosis in patients treated with cilostazol. Circulation. 2005;112:2826–32.
Lee SW, Chun KJ, Park SW, Kim HS, Kim YH, Yun SC, et al. Comparison of triple antiplatelet therapy and dual antiplatelet therapy in patients at high risk of restenosis after drug-eluting stent implantation (from the DECLARE-DIABETES and -LONG Trials). Am J Cardiol. 2010;105:168–73.
Lee SW, Park SW, Hong MK, Kim YH, Lee BK, Song JM, et al. Triple versus dual antiplatelet therapy after coronary stenting: impact on stent thrombosis. J Am Coll Cardiol. 2005;46:1833–7.
Jeong YH, Lee SW, Choi BR, Kim IS, Seo MK, Kwak CH, et al. Randomized comparison of adjunctive cilostazol versus high maintenance dose clopidogrel in patients with high post-treatment platelet reactivity: results of the ACCEL-RESISTANCE (adjunctive cilostazol versus high maintenance dose clopidogrel in patients with clopidogrel resistance) randomized study. J Am Coll Cardiol. 2009;53:1101–9.
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;71:1685–90.
Han Y, Li Y, Wang S, Jing Q, Wang Z, Wang D, et al. 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;157:733–9.
Kimura T, Morimoto T, Nakagawa Y, Tamura T, Kadota K, Yasumoto H, et al. Antiplatelet therapy and stent thrombosis after sirolimus-eluting stent implantation. Circulation. 2009;119:987–95.
Serruys PW, Ong AT, van Herwerden LA, Sousa JE, Jatene A, Bonnier JJ, et al. Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: the final analysis of the arterial revascularization therapies study (ARTS) randomized trial. J Am Coll Cardiol. 2005;46:575–81.
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;356:1020–9.
Kim JY, Lee K, Shin M, Ahn M, Choe H, Yoo BS, et al. Cilostazol could ameliorate platelet responsiveness to clopidogrel in patients undergoing primary percutaneous coronary intervention. Circ J. 2007;71:1867–72.
Shim CY, Yoon SJ, Park S, Kim JS, Choi JR, Ko YG, et al. The clopidogrel resistance can be attenuated with triple antiplatelet therapy in patients undergoing drug-eluting stents implantation. Int J Cardiol. 2009;134:351–5.
Biondi-Zoccai GG, Lotrionte M, Anselmino M, Moretti C, Agostoni P, Testa L, et al. Systematic review and meta-analysis of randomized clinical trials appraising the impact of cilostazol after percutaneous coronary intervention. Am Heart J. 2008;155:1081–9.
Jennings DL, Kalus JS. Addition of cilostazol to aspirin and a thienopyridine for prevention of restenosis after coronary artery stenting: a meta-analysis. J Clin Pharmacol. 2010;50:415–21.
Lee SW, Park SW, Kim YH, Yun SC, Park DW, Lee CW, 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;51:1181–7.
Singh I, Shafiq N, Pandhi P, Reddy S, Pattanaik S, Sharma Y, et al. Triple antiplatelet therapy versus dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: an evidence-based approach to answering a clinical query. Br J Clin Pharmacol. 2009;68:4–13.
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;150:228–30.
Lee SW, Park SW, Kim YH, Yun SC, Park DW, Lee CW, et al. 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;57:1264–70.
Suh JW, Lee SP, Park KW, Lee HY, Kang HJ, Koo BK, et al. 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;57:280–9.
Soga Y, Yokoi H, Kawasaki T, Nakashima H, Tsurugida M, Hikichi Y, et al. Efficacy of cilostazol after endovascular therapy for femoropopliteal artery disease in patients with intermittent claudication. J Am Coll Cardiol. 2009;53:48–53.
Takigawa T, Matsumaru Y, Hayakawa M, Nemoto S, Matsumura A. Cilostazol reduces restenosis after carotid artery stenting. J Vasc Surg. 2010;51:51–6.
Park KH, Jeong MH, Lee MG, Ko JS, Lee SE, Kang WY, et al. Efficacy of triple anti-platelet therapy including cilostazol in acute myocardial infarction patients undergoing drug-eluting stent implantation. Korean Circ J. 2009;39:190–7.
Chen KY, Rha SW, Li YJ, Poddar KL, Jin Z, Minami Y, et al. Triple versus dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation. 2009;119:3207–14.
Acknowledgments
We thank the members of the cardiac catheterization laboratories of the participating centers and the clinical research coordinators. This study was supported by Cordis Cardiology Japan, a Johnson & Johnson company. The study sponsor was not involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Conflict of interests
Dr Kimura serves as an advisory board member and member of the speakers’ bureau for Cordis Cardiology and has received honoraria from Cordis Cardiology. The remaining authors report no potential conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
On Behalf of the j-Cypher Registry Investigators.
This study was supported by Cordis Cardiology Japan, a Johnson & Johnson company.
Appendix
Appendix
A complete list of the investigators and committees involved in the j-Cypher registry has been published previously [8].
Rights and permissions
About this article
Cite this article
Nakao, T., Kimura, T., Morimoto, T. et al. The long-term efficacy of cilostazol in addition to dual antiplatelet therapy after sirolimus-eluting stent implantation for Japanese patients: an analysis of the 3-year follow-up outcomes from the j-Cypher registry. Cardiovasc Interv and Ther 27, 161–167 (2012). https://doi.org/10.1007/s12928-012-0105-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12928-012-0105-4