非ST段抬高型急性冠状动脉综合征患者接受择期经皮冠状动脉介入治疗术后抗凝治疗对预后的影响

The impact of anticoagulation therapy after elective percutaneous coronary intervention on prognosis in patients with non-ST-segment elevation acute coronary syndrome

目的探究择期经皮冠状动脉介入治疗(PCI)术后抗凝治疗对非ST段抬高型急性冠状动脉综合征(NSTE-ACS)患者近期及远期预后的影响。方法磺达肝癸钠应用于非ST段抬高型急性冠状动脉综合征患者的真实世界研究(REFOCAS)是一项多中心、前瞻性、实操性临床研究,自2019年7月至2021年7月在全国88家医院入选了8066例接受非紧急侵入PCI治疗的成年患者,本研究纳入了REFOCAS研究中接受择期PCI手术治疗的NSTE-ACS患者,入组后按2∶1的顺序接受磺达肝癸钠和低分子肝素抗凝,根据PCI术后是否接受抗凝治疗分为术后抗凝组与术后未抗凝组,术后抗凝组接受磺达肝癸钠(2.5 mg/d)或低分子肝素(1 mg/kg,2次/d)抗凝治疗2~8 d或直至出院。对患者进行30 d、180 d的随访,记录净不良临床和脑血管事件(NACCE),包括全因死亡、再发心肌梗死、非致死性卒中、出血学术研究联合会(BARC)≥2型出血发生情况,以及主要心血管不良事件(MACE),包括全因死亡、再发心肌梗死、非致死性卒中。采用倾向性评分匹配法(PSM)匹配出875对患者,使用Kaplan-Meier生存分析比较匹配前后两组的近期和远期预后差异,同时采用多因素Cox回归分析术后抗凝治疗对预后的影响,最后在各亚组中进行多因素Cox回归分析。结果最终纳入3293例接受择期PCI治疗并完成6个月随访的NSTE-ACS患者,其中抗凝组2212(67.2%)例,术后未抗凝组1081(32.8%)例。采用PSM匹配出875对患者并对这两组的基线和预后进行分析,匹配后两组基线可比(P均<0.05)。术后抗凝组与术后未抗凝组相比较,30 d NACCE发生率较低[2.5%(56例)比5.1%(55例),P<0.001],院内及30 d NACCE、MACE、BARC≥2型出血、卒中事件发生率均显著降低(P均<0.05),而再发心肌梗死、全因死亡事件差异无统计学意义(P>0.05)。术后抗凝组180 d NACCE、BARC≥2型出血、再发心梗事件发生率显著降低(P均<0.05),而MACE、全因死亡、卒中的发生率差异无统计学意义(P>0.05)。PSM后显示,术后抗凝组30 d NACCE发生率降低[3.0%(26例)比5.0%(44例),P=0.028],院内、180 d发生NACCE、180 d发生BARC≥2型出血事件的风险(P均<0.05)。多因素Cox回归分析提示,术后接受抗凝治疗是院内NACCE和MACE、30 d NACCE、MACE和BARC≥2型出血,180 d NACCE和BARC≥2型出血的独立保护因素。亚组分析提示,PCI术后使用磺达肝癸钠抗凝治疗较术后未抗凝组,能降低院内NACCE、180 d NACCE风险(P均<0.05)。结论行择期PCI治疗的NSTE-ACS患者接受术后抗凝治疗能有效降低院内、30 d、180 d发生NACCE的风险,对减少BARC≥2型出血事件也有积极作用。

Objective To investigate the impact of anticoagulation therapy after non-emergency percutaneous coronary intervention(PCI)on the short-term and long-term prognosis of non-ST-segment elevation acute coronary syndrome(NSTE-ACS)patients.Methods The Real World Study(REFOCAS)of fondaparinux applied to patients with non-ST-segment elevation acute coronary syndrome was a multicenter,prospective,and practical clinical study.From July 2019 to July 2021,a total of 8,066 adult patients who underwent non-emergency PCI treatment were selected from 88 hospitals nationwide.This study included NSTE-ACS patients who underwent non-emergency PCI in the REFOCAS study.The patients received anticoagulation with fondaparinux and low molecular weight heparin(LMWH)in a 2∶1 order.They were divided into the post-PCI anticoagulation group and non post-PCI anticoagulation group based on whether they received anticoagulation treatment after PCI.The post-PCI anticoagulation group received anticoagulation with fondaparinux(2.5 mg/d)or LMWH(1 mg/kg,twice a day)for 2-8 days or until discharge.The patients were followed up for 30 and 180 days to record the occurrence of NACCE(including all cause death,reinfarction,non fatal stroke and BARC≥2 type bleeding)and MACE(including all cause death,reinfarction,non fatal stroke).875 pairs of the patients were matched using propensity score matching(PSM)method,and Kaplan-Meier survival analysis was used to compare the short-term and long-term prognosis differences between the two groups before and after matching.Multivariate Cox regression analysis was used to analyze the impact of post-PCI anticoagulation treatment on prognosis.Finally,multivariate Cox regression analysis was performed in each subgroup.Results The final inclusion comprised 3,293 NSTE-ACS patients who underwent non-emergency PCI and completed a 6-month follow-up.There were 2212(67.2%)patients in the post-PCI anticoagulation group and 1081(32.8%)patients in the non post-PCI anticoagulation group.There were 875 pairs of patients matched using the propensity score matching method,and the baseline characteristics and prognosis of the two groups were analyzed.After matching,the baseline characteristics of the two groups were found to be comparable(P<0.05).Compared with the non post-PCI anticoagulation group,the incidence of 30 days NACCE decreased[56(2.5%)vs.55(5.1%),P<0.001]and MACE,BARC≥2 type bleeding,and stroke events in the hospital and 30 days were also lower(all P<0.05)in the post-PCI anticoagulation group,while there was no statistically significant difference in reinfarction and all cause death events(P>0.05).The incidence of NACCE,BARC≥2 type bleeding and reinfarction events decreased in the post-PCI anticoagulation group in 180 days(all P<0.05),while there was no statistically significant difference in the incidence of MACE,all cause death and stroke(all P>0.05).After PSM,the risk of 30-day NACCE[26(3.0%)vs.44(5.0%),P=0.028],the incidences of NACCE in the hospital and 180 daysand BARC≥2 type bleeding events in 180 days decreased(all P<0.05)in the post-PCI anticoagulation group.Multivariate Cox regression analysis showed that post-PCI anticoagulation was an independent protective factor for hospital NACCE and MACE,30 days NACCE,MACE,and BARC≥2 bleeding,as well as 180 days NACCE and BARC≥2 bleeding.The subgroup analysis suggested that post-PCI use of fondaparinux reduced the risk of NACCE in hospital and 180 days NACCE compared to the non post-PCI anticoagulation group(P<0.05).Conclusions Post-PCI anticoagulation therapy can effectively reduce the risk of in-hospital,30 days and 180 days NACCE in NSTE-ACS patients undergoing non-emergency PCI,and it also has a positive effect on reducing BARC≥2 type bleeding events.