Article

The efficacy and safety of cilostazol as an alternative to aspirin in Chinese patients with aspirin intolerance after coronary stent implantation: a combined clinical study and computational system pharmacology analysis

Authors: Ying XUE1,2,3, Zhi-wei FENG2,3, Xiao-ye LI4, Zi-heng HU2,3, Qing XU4, Zi WANG5, Jia-hui CHENG6, Hong-tao SHI6, Qi-bing WANG6, Hong-yi WU6, Xiang-Qun XIE7, Qian-zhou LV1
1 Department of Clinical Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, China
2 Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy; NIH National Center of Excellence for
3 Computational Drug Abuse Research; Drug Discovery Institute; Departments of Computational Biology and Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
4 Department of Clinical Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
5 School of Pharmacy, Fudan University, Shanghai 201203, China
6 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
7 Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy; NIH National Center of Excellence for Computational Drug Abuse Research; Drug Discovery Institute; Departments of Computational Biology and Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Corresponding to: Hong-yi WU: wu.hongyi@zs-hospital.sh.cn, Xiang-Qun XIE: xix15@pitt.edu, Qian-zhou LV: Lv.qianzhou@zs-hospital.sh.cn,
DOI: 10.1038/aps.2017.85
Received: 27 February 2017
Accepted: 19 May 2017
Advance online: 21 September 2017

Abstract

Abstract
Dual antiplatelet therapy (DAT) with aspirin and clopidogrel is the standard regimen to achieve rapid platelet inhibition and prevent thrombotic events. Currently, little information is available regarding alternative antiplatelet therapy in patients with an allergy or intolerance to aspirin. Although cilostazol is already a common alternative to aspirin in clinical practice in China, its efficacy and safety remain to be determined. We retrospectively analyzed 613 Chinese patients who had undergone primary percutaneous coronary intervention (PCI). Among them, 405 patients received standard DAT (aspirin plus clopidogrel) and 205 patients were identified with intolerance to aspirin and received alternative DAT (cilostazol plus clopidogrel). There were no significant differences between the two groups in their baseline clinical characteristics. The main outcomes of the study included major adverse cardiac events (MACEs) and bleeding events during 12 months of follow-up. The MACEs endpoint was reached in 10 of 205 patients treated with cilostazol (4.9%) and in 34 of 408 patients treated with aspirin (8.3%). No statistically significant difference was observed in MACEs between the two groups. However, patients in the cilostazol group had less restenosis than did patients in the aspirin group (1.5% vs4.9%, P=0.035). The occurrence of bleeding events tended to be lower in the cilostazol group (0.49% vs 2.7%, P=0.063). These clinical observations were further analyzed using network system pharmacology analysis, and the outcomes were consistent with clinical observations and preclinical data reports. We conclude that in Chinese patients with aspirin intolerance undergoing coronary stent implantation, the combination of clopidogrel with cilostazol may be an efficacious and safe alternative to the standard DAT regimen.
Keywords: dual antiplatelet therapy; aspirin; intolerance; cilostazol; percutaneous coronary intervention; major adverse cardiac events; network system pharmacology