西洛他唑辅助双联抗血小板治疗对急性心肌梗死患者内皮祖细胞动员的影响：一项随机、安慰剂对照的EPISODE试验

Adjunctive Cilostazol to Dual Antiplatelet Therapy to Enhance Mobilization of Endothelial Progenitor Cell in Patients with Acute Myocardial Infarction: A Randomized, Placebo-Controlled EPISODE Trial.

作者信息

Park Yongwhi, Kim Jin Hyun, Kim Tae Ho, Koh Jin-Sin, Hwang Seok-Jae, Hwang Jin-Yong, Jeong Young-Hoon

机构信息

Department of Internal Medicine, School of Medicine, Gyeongsang National University, Jinju 52828, Korea.

Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea.

出版信息

J Clin Med. 2020 Jun 1;9(6):1678. doi: 10.3390/jcm9061678.

BACKGROUND

Endothelial progenitor cells (EPCs) have the potential to protect against atherothrombotic event occurrences. There are no data to evaluate the impact of cilostazol on EPC levels in high-risk patients.

METHODS

We conducted a randomized, double-blind, placebo-controlled trial to assess the effect of adjunctive cilostazol on EPC mobilization and platelet reactivity in patients with acute myocardial infarction (AMI). Before discharge, patients undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive cilostazol SR capsule (200-mg) a day ( = 30) or placebo ( = 30) on top of dual antiplatelet therapy (DAPT) with clopidogrel and aspirin. Before randomization (baseline) and at 30-day follow-up, circulating EPC levels were analyzed using flow cytometry and hemostatic measurements were evaluated by VerifyNow and thromboelastography assays. The primary endpoint was the relative change in EPC levels between baseline and 30-day.

RESULTS

At baseline, there were similar levels of EPC counts between treatments, whereas patients with cilostazol showed higher levels of EPC counts compared with placebo after 30 days. Cilostazol versus placebo treatment displayed significantly higher changes in EPC levels between baseline and follow-up (ΔCD133/KDR: difference 216%, 95% confidence interval (CI) 44~~388%, = 0.015; ΔCD34/KDR: difference 183%, 95% CI 25~~342%, = 0.024). At 30-day follow-up, platelet reactivity was lower in the cilostazol group compared with the placebo group (130 ± 45 versus 169 ± 62 P2Y12 Reaction Unit, = 0.009). However, there were no significant correlations between the changes of EPC levels and platelet reactivity.

CONCLUSION

Adjunctive cilostazol on top of clopidogrel and aspirin versus DAPT alone is associated with increased EPC mobilization and decreased platelet reactivity in AMI patients, suggesting its pleiotropic effects against atherothrombotic events (NCT04407312).

背景

内皮祖细胞（EPCs）具有预防动脉粥样硬化血栓形成事件发生的潜力。目前尚无数据评估西洛他唑对高危患者EPC水平的影响。

方法

我们进行了一项随机、双盲、安慰剂对照试验，以评估辅助使用西洛他唑对急性心肌梗死（AMI）患者EPC动员和血小板反应性的影响。出院前，接受经皮冠状动脉介入治疗（PCI）的患者在接受氯吡格雷和阿司匹林双重抗血小板治疗（DAPT）的基础上，被随机分配接受西洛他唑缓释胶囊（200毫克）每日一次（n = 30）或安慰剂（n = 30）。在随机分组前（基线）和30天随访时，使用流式细胞术分析循环EPC水平，并通过VerifyNow和血栓弹力图检测评估止血指标。主要终点是基线和30天时EPC水平的相对变化。

结果

基线时，各治疗组间EPC计数水平相似，而30天后，接受西洛他唑治疗的患者EPC计数水平高于安慰剂组。西洛他唑与安慰剂治疗相比，基线和随访期间EPC水平的变化显著更高（ΔCD133/KDR：差异216%，95%置信区间（CI）44~~388%，P = 0.015；ΔCD34/KDR：差异183%，95%CI 25~~342%，P = 0.024）。在30天随访时，西洛他唑组的血小板反应性低于安慰剂组（130±45对169±62 P2Y12反应单位，P = 0.009）。然而，EPC水平变化与血小板反应性之间无显著相关性。