Department of Clinical Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
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.
Acta Pharmacol Sin. 2018 Feb;39(2):205-212. doi: 10.1038/aps.2017.85. Epub 2017 Sep 21.
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% vs 4.9%, 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.
双联抗血小板治疗（DAT），即阿司匹林加氯吡格雷，是实现快速血小板抑制和预防血栓事件的标准方案。目前，对于阿司匹林过敏或不耐受的患者，替代抗血小板治疗的相关信息有限。虽然在中国的临床实践中，西洛他唑已经是阿司匹林的常见替代药物，但它的疗效和安全性仍有待确定。我们回顾性分析了 613 例接受经皮冠状动脉介入治疗（PCI）的中国患者。其中，405 例患者接受标准 DAT（阿司匹林加氯吡格雷）治疗，205 例患者对阿司匹林不耐受，接受替代 DAT（西洛他唑加氯吡格雷）治疗。两组患者的基线临床特征无显著差异。研究的主要终点是 12 个月随访期间的主要不良心脏事件（MACEs）和出血事件。在接受西洛他唑治疗的 205 例患者中，有 10 例（4.9%）达到了 MACEs 终点，在接受阿司匹林治疗的 408 例患者中，有 34 例（8.3%）达到了 MACEs 终点。两组之间 MACEs 无统计学差异。然而，西洛他唑组的再狭窄率低于阿司匹林组（1.5% vs 4.9%，P=0.035）。西洛他唑组出血事件的发生率较低（0.49% vs 2.7%，P=0.063）。这些临床观察结果进一步通过网络系统药理学分析进行了分析，结果与临床观察和临床前数据报告一致。我们的结论是，对于在中国接受冠状动脉支架植入术的阿司匹林不耐受患者，氯吡格雷联合西洛他唑可能是标准 DAT 方案的一种有效且安全的替代方案。
