真实世界急性冠状动脉综合征或经皮冠状动脉介入治疗术后患者替格瑞洛抗血小板降阶治疗的临床转归

De-escalation of antiplatelet therapy in patients with acute coronary syndrome or after undergoing percutaneous coronary intervention:a real-world analysis of clinical outcomes

摘要:

目的 探讨真实世界急性冠状动脉综合征(ACS)或经皮冠状动脉介入治疗(PCI)术后患者由替格瑞洛降阶为氯吡格雷抗血小板治疗的临床转归。方法 连续募集2013年10月至2016年8月于中国人民解放军总医院第一医学中心心血管内科住院期间接受替格瑞洛联合阿司匹林抗血小板治疗,并于住院期间或出院后1年内将替格瑞洛降阶为氯吡格雷的ACS或PCI术后患者746例。根据替格瑞洛降阶治疗时间,将患者分为急性期组(≤1个月,n=212)和非急性期组(1～3个月,n=262；3～6个月,n=156；6～12个月,n=116)。对所有患者进行1年随访。分析各组患者降阶治疗原因,比较各组患者主要终点事件[1年内净临床不良事件:全因死亡、非致死性心肌梗死、非致死性脑卒中、靶血管重建及出血学会研究会(BARC)定义的2、3、5型出血事件构成的复合终点事件]及次要终点事件(心血管缺血事件和BACR 2、3、5型出血事件)发生差异。采用SPSS 26.0软件进行统计分析。多因素logistic回归分析对比不同时间段行替格瑞洛降阶治疗后主要终点事件和次要终点事件的发生风险。结果 急性期组降阶治疗的主要原因是冠状动脉造影未见严重狭窄(23.1%),非急性期组降阶治疗的主要原因是无法获取替格瑞洛(41.9%)。急性期组1年内净临床不良事件发生率略高于非急性期1～3个月组,但差异无统计学意义(14.6% 和 12.2%；HR=0.72,95%CI 0.41～1.26；P=0.252)。非急性期1～3个月组的1年内净临床不良事件显著低于3～6个月组(12.2%和19.2%；HR=1.90,95%CI 1.07～3.37；P=0.029)及6～12个月组(12.2% 和21.6%；HR=1.48,95%CI 1.10～2.00；P=0.010)。各组间1年内心血管缺血事件比较,差异无统计学意义(P≥0.05)。非急性期1～3个月组的1年内出血事件显著低于6～12个月组(9.2%和15.5%; HR＝1.42,95%CI 1.01～2.00；P=0.044)。结论 真实世界中ACS或PCI术后患者在非急性期1～3个月内进行替格瑞洛抗血小板降阶治疗能够获得最佳的临床净获益。

Abstract:

Objective To investigate the clinical outcomes of de-escalation from ticagrelor to clopidogrel in patients with acute coronary syndrome (ACS) or those after undergoing percutaneous coronary intervention (PCI) in the real world. Methods A total of 746 consecutive inpatients with ACS or after PCI who received combined ticagrelor and aspirin therapy in the Department of Cardiology of Chinese PLA General Hospital from October 2013 to August 2016 and then de-escalated from ticagrelor to clopidogrel during hospitalization or within 1 year after discharge were recruited in this study. According to the de-escalation time, the patients were divided into acute phase group (≤1 month, n=212) and non-acute phase group (1-3 months, n=262; 3-6 months, n=156; 6－12 months, n=116). All patients were followed up for 1 year to analyze the causes of de-escalation. The incidences of primary endpoints [net clinical adverse events within 1 year:a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel reconstruction and bleeding type 2,3 or 5 according to the Bleeding Academic Research Consortium (BARC) criteria] and secondary endpoints (cardiovascular ischemic events and BARC type 2,3 or 5 bleeding events) were compared between the groups. SPSS statistics 26.0 was used for data analysis. Multivariate logistic regression analysis was employed to evaluate the risk of primary endpoints and secondary endpoints after the de-escalation at different time periods. Results The main reason for de-escalation was no serious stenosis on coronary angiogram in the acute phase group (23.1%), and was ticagrelor unavailable in the non-acute phase group (41.9%). The incidence rate of 1-year net clinical adverse events was slightly higher in the acute phase group than the non-acute 1-3 months group (14.6% vs 12.2%, HR=0.72,95%CI 0.41-1.26; P=0.252), but there was no statistical difference. The incidence rate in the non-acute 1-3 months group was significantly lower than that of the 3-6 months group (12.2% vs 19.2%; HR=1.90,95%CI 1.07-3.37; P=0.029) and that of the 6-12 months group (12.2% vs 21.6%; HR=1.48,95%CI 1.10－2.00; P=0.010). There was no significant difference in the incidence of 1-year cardiovascular ischemic events among the groups (P≥0.05). The rate of 1-year bleeding events was significantly lower in the non-acute 1-3 months group than the 6-12 months group (9.2% vs 15.5%; HR=1.42,95%CI 1.01-2.00; P=0.044). Conclusion In the real world, the patients with ACS or after PCI can obtain best net clinical benefit from de-escalation of ticagrelor to clopidogrel in an early non-acute phase (1-3 months).