辨证应用中成药干预ACS介入治疗后女性患者:全国多中心前瞻性队列研究

Intervention of traditional Chinese patent medicine based on syndrome differentiation in female patients after percutaneous coronary intervention due to acute coronary syndrome:a nationwide multicenter prospective cohort study

目的评价辨证应用中成药干预急性冠脉综合征(ACS)经皮冠状动脉介入治疗(PCI)后女性患者的疗效和安全性。方法研究人群来自CPM(Chinese Patent Medicine)试验,CPM试验是一项多中心前瞻性队列研究,于2012年2月至2015年12月在中国内地40家中心纳入患者,以是否辨证使用中成药为暴露因素。本研究从CPM试验中入选PCI后的女性ACS且完成术后36个月随访的患者,分为常规治疗组(采用指南推荐常规西药治疗)和辨证应用中成药组(在常规西药治疗基础上气虚血瘀证加用芪参益气滴丸,心血瘀阻证加用冠心丹参滴丸,痰瘀互结证加用丹蒌片)。主要终点事件为包括心血管死亡、非致命性心肌梗死、再次紧急血运重建术的复合终点事件。次要终点事件为包括因ACS再住院、心力衰竭、卒中和其他血栓事件的复合终点事件。记录不良事件的发生情况。采用Cox比例风险模型评估辨证应用中成药对终点事件的影响,并通过与倾向性评分匹配分析结果比较进行敏感性分析。结果共纳入分析748例女性ACS PCI后患者,年龄(63.2±8.3)岁,辨证应用中成药组370例,常规治疗组378例。辨证应用中成药组及常规治疗组分别有37例(10.0%)和58例(15.3%)发生主要终点事件;Cox回归分析结果显示,校正混杂因素后,辨证应用中成药组主要终点事件发生风险低于常规治疗组(校正后HR=0.62,95%CI 0.40~0.96,P=0.031)。两组分别有38例(10.3%)和57例(15.1%)发生次要终点事件;Cox回归分析结果显示,校正混杂因素后,辨证应用中成药组次要终点事件发生风险低于常规治疗组(校正后HR=0.56,95%CI 0.37~0.87,P=0.001)。倾向性评分匹配分析结果显示,辨证应用中成药组主要终点事件(HR=0.62,95%CI 0.40~0.97,P=0.033)及次要终点事件(HR=0.56,95%CI 0.37~0.87,P=0.009)发生风险较常规治疗组低,与前述一致。辨证应用中成药组及常规治疗组的不良事件发生率差异无统计学意义[12.4%(46/370)比10.3%(39/378),P=0.362]。结论在西医常规治疗的基础上,辨证应用中成药可降低ACS PCI后女性患者终点事件发生风险,且未发现明显不良反应。

ObjectiveTo evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention(PCI)due to acute coronary syndrome(ACS).MethodsThe study population was from the Chinese Patent Medicine(CPM)trial.CPM trial was a multicenter prospective cohort study,which enrolled patients from 40 centers in China's Mainland between February 2012 and December 2015,with the discriminative use of Chinese patent medicines as the exposure factor.Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis,and were divided into a conventional treatment group(using conventional western medicine recommended by the guidelines)and a group with the discriminative use of proprietary Chinese medicines(on the basis of conventional western medicine treatment,discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome,Guanxin Danshen dropping pills for blood stasis syndrome,and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine).The primary endpoint event was a composite endpoint event including cardiovascular death,nonfatal myocardial infarction,and emergency revascularization surgery.Secondary endpoint events were composite endpoint events including readmission for ACS,heart failure,stroke,and other thrombotic events.Adverse events were collected.Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events,and sensitivity analysis was performed by comparing the results with propensity score matching analysis.ResultsA total of 748 female ACS post-PCI patients were included in the analysis,aged(63.2±8.3)years.There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group.There were 37 cases(10.0%)and 58 cases(15.3%)of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group,respectively.Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors(adjusted HR=0.62,95%CI 0.40-0.96,P=0.031).There were 38(10.3%)and 57(15.1%)cases of secondary endpoint events in the two groups,respectively.Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders(adjusted HR=0.56,95%CI 0.37-0.87,P=0.001).The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint(HR=0.62,95%CI 0.40-0.97,P=0.033)and second endpoint(HR=0.56,95%CI 0.37-0.87,P=0.009)significantly.There was no significant difference in adverse events between the two groups(12.4%(46/370)vs.10.3%(39/378),P=0.362).ConclusionOn the basis of conventional western medicine treatment,discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.