Abstract：
Previous randomised trials of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) have reported conflicting results, in part because of treatment with different pharmacological regimens. We designed a large-scale trial examining bivalirudin with a post-PCI high-dose infusion compared with heparin alone, the regimens that previous studies have shown to have the best balance of safety and efficacy.
BRIGHT-4 was an investigator-initiated, open-label, randomised controlled trial conducted at 87 clinical centres in 63 cities in China. Patients with STEMI undergoing primary PCI with radial artery access within 48 h of symptom onset who had not received previous fibrinolytic therapy, anticoagulants, or glycoprotein IIb/IIIa inhibitors were randomly assigned (1:1) to receive bivalirudin with a post-PCI high-dose infusion for 2-4 h or unfractionated heparin monotherapy. There was no masking. Glycoprotein IIb/IIIa inhibitor use was reserved for procedural thrombotic complications in both groups. The primary endpoint was a composite of all-cause mortality or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. This trial is registered with ClinicalTrials.gov (NCT03822975), and is ongoing.
Between Feb 14, 2019, and April 7, 2022, a total of 6016 patients with STEMI undergoing primary PCI were randomly assigned to receive either bivalirudin plus a high-dose infusion after PCI (n=3009) or unfractionated heparin monotherapy (n=3007). Radial artery access was used in 5593 (93·1%) of 6008 patients. Compared with heparin monotherapy, bivalirudin reduced the 30-day rate of the primary endpoint (132 events [4·39%] in the heparin group vs 92 events [3·06%] in the bivalirudin group; difference, 1·33%, 95% CI 0·38-2·29%; hazard ratio [HR] 0·69, 95% CI 0·53-0·91; p=0·0070). All-cause mortality within 30 days occurred in 118 (3·92%) heparin-assigned patients and in 89 (2·96%) bivalirudin-assigned patients (HR 0·75; 95% CI 0·57-0·99; p=0·0420), and BARC types 3-5 bleeding occurred in 24 (0·80%) heparin-assigned patients and five (0·17%) bivalirudin-assigned patients (HR 0·21; 95% CI 0·08-0·54; p=0·0014). There were no significant differences in the 30-day rates of reinfarction, stroke, or ischaemia-driven target vessel revascularisation between the groups. Within 30 days, stent thrombosis occurred in 11 (0·37%) of bivalirudin-assigned patients and 33 (1·10%) of heparin-assigned patients (p=0·0015).
In patients with STEMI undergoing primary PCI predominantly with radial artery access, anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2-4 h significantly reduced the 30-day composite rate of all-cause mortality or BARC types 3-5 major bleeding compared with heparin monotherapy.
Chinese Society of Cardiology Foundation (CSCF2019A01), and a research grant from Jiangsu Hengrui Pharmaceuticals.
BRIGHT-4 was an investigator-initiated, open-label, randomised controlled trial conducted at 87 clinical centres in 63 cities in China. Patients with STEMI undergoing primary PCI with radial artery access within 48 h of symptom onset who had not received previous fibrinolytic therapy, anticoagulants, or glycoprotein IIb/IIIa inhibitors were randomly assigned (1:1) to receive bivalirudin with a post-PCI high-dose infusion for 2-4 h or unfractionated heparin monotherapy. There was no masking. Glycoprotein IIb/IIIa inhibitor use was reserved for procedural thrombotic complications in both groups. The primary endpoint was a composite of all-cause mortality or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. This trial is registered with ClinicalTrials.gov (NCT03822975), and is ongoing.
Between Feb 14, 2019, and April 7, 2022, a total of 6016 patients with STEMI undergoing primary PCI were randomly assigned to receive either bivalirudin plus a high-dose infusion after PCI (n=3009) or unfractionated heparin monotherapy (n=3007). Radial artery access was used in 5593 (93·1%) of 6008 patients. Compared with heparin monotherapy, bivalirudin reduced the 30-day rate of the primary endpoint (132 events [4·39%] in the heparin group vs 92 events [3·06%] in the bivalirudin group; difference, 1·33%, 95% CI 0·38-2·29%; hazard ratio [HR] 0·69, 95% CI 0·53-0·91; p=0·0070). All-cause mortality within 30 days occurred in 118 (3·92%) heparin-assigned patients and in 89 (2·96%) bivalirudin-assigned patients (HR 0·75; 95% CI 0·57-0·99; p=0·0420), and BARC types 3-5 bleeding occurred in 24 (0·80%) heparin-assigned patients and five (0·17%) bivalirudin-assigned patients (HR 0·21; 95% CI 0·08-0·54; p=0·0014). There were no significant differences in the 30-day rates of reinfarction, stroke, or ischaemia-driven target vessel revascularisation between the groups. Within 30 days, stent thrombosis occurred in 11 (0·37%) of bivalirudin-assigned patients and 33 (1·10%) of heparin-assigned patients (p=0·0015).
In patients with STEMI undergoing primary PCI predominantly with radial artery access, anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2-4 h significantly reduced the 30-day composite rate of all-cause mortality or BARC types 3-5 major bleeding compared with heparin monotherapy.
Chinese Society of Cardiology Foundation (CSCF2019A01), and a research grant from Jiangsu Hengrui Pharmaceuticals.
摘要：
先前在接受直接经皮冠状动脉介入治疗（PCI）的ST段抬高型心肌梗死（STEMI）患者中使用比伐卢定与肝素的随机试验报道了相互矛盾的结果，部分原因是使用不同的药物治疗方案。我们设计了一项大规模试验，检查比伐卢定在PCI术后高剂量输注与单独使用肝素相比，以前的研究表明，在安全性和有效性之间具有最佳平衡。
BRIGHT-4是由调查员发起的,开放标签，在中国63个城市的87个临床中心进行的随机对照试验.在症状发作后48小时内接受经桡动脉途径的原发性PCI的STEMI患者，以前没有接受过纤溶治疗。抗凝剂,或糖蛋白IIb/IIIa抑制剂被随机分配(1:1)接受比伐卢定PCI术后高剂量输注2-4h或普通肝素单药治疗.没有面具。在两组中，糖蛋白IIb/IIIa抑制剂的使用保留用于手术血栓并发症。主要终点是全因死亡率或出血学术研究联盟（BARC）30天时3-5型出血的复合终点。该试验已在ClinicalTrials.gov（NCT03822975）注册，并且正在进行中。
在2019年2月14日至2022年4月7日之间，共有6016例接受原发性PCI的STEMI患者被随机分配接受PCI后比伐卢定加高剂量输注（n=3009）或普通肝素单药治疗（n=3007）。6008例患者中有5593例（93·1％）使用了桡动脉通路。与肝素单药治疗相比，比伐卢定降低了主要终点的30天发生率(肝素组132例[4·39%]vs比伐卢定组92例[3·06%];1·33%，95%CI0·38-2·29%；危险比[HR]0·69，95%CI0·53-0·91；p=0·0070）。30天内的全因死亡率发生在118例（3·92％）肝素分配的患者和89例（2·96％）比伐卢定分配的患者中（HR0·75；95％CI0·57-0·99；p=0·0420），和BARC3-5型出血发生在24例(0·80%)肝素分配的患者和5例(0·17%)比伐卢定分配的患者中(HR0·21;95%CI0·08-0·54;p=0·0014).30天的再梗死率没有显着差异，中风,或缺血驱动的目标血管血运重建。30天内,支架内血栓形成发生在11例(0·37%)比伐卢定分配的患者和33例(1·10%)肝素分配的患者中(p=0·0015)。
在接受以桡动脉途径为主的原发性PCI的STEMI患者中，与肝素单药治疗相比,比伐卢定联合PCI术后高剂量输注2~4h抗凝治疗可显著降低30日全因死亡率或BARC3~5型大出血的复合发生率.
中国心脏病学会基金会(CSCF2019A01),和江苏恒瑞医药的科研经费。
BRIGHT-4是由调查员发起的,开放标签，在中国63个城市的87个临床中心进行的随机对照试验.在症状发作后48小时内接受经桡动脉途径的原发性PCI的STEMI患者，以前没有接受过纤溶治疗。抗凝剂,或糖蛋白IIb/IIIa抑制剂被随机分配(1:1)接受比伐卢定PCI术后高剂量输注2-4h或普通肝素单药治疗.没有面具。在两组中，糖蛋白IIb/IIIa抑制剂的使用保留用于手术血栓并发症。主要终点是全因死亡率或出血学术研究联盟（BARC）30天时3-5型出血的复合终点。该试验已在ClinicalTrials.gov（NCT03822975）注册，并且正在进行中。
在2019年2月14日至2022年4月7日之间，共有6016例接受原发性PCI的STEMI患者被随机分配接受PCI后比伐卢定加高剂量输注（n=3009）或普通肝素单药治疗（n=3007）。6008例患者中有5593例（93·1％）使用了桡动脉通路。与肝素单药治疗相比，比伐卢定降低了主要终点的30天发生率(肝素组132例[4·39%]vs比伐卢定组92例[3·06%];1·33%，95%CI0·38-2·29%；危险比[HR]0·69，95%CI0·53-0·91；p=0·0070）。30天内的全因死亡率发生在118例（3·92％）肝素分配的患者和89例（2·96％）比伐卢定分配的患者中（HR0·75；95％CI0·57-0·99；p=0·0420），和BARC3-5型出血发生在24例(0·80%)肝素分配的患者和5例(0·17%)比伐卢定分配的患者中(HR0·21;95%CI0·08-0·54;p=0·0014).30天的再梗死率没有显着差异，中风,或缺血驱动的目标血管血运重建。30天内,支架内血栓形成发生在11例(0·37%)比伐卢定分配的患者和33例(1·10%)肝素分配的患者中(p=0·0015)。
在接受以桡动脉途径为主的原发性PCI的STEMI患者中，与肝素单药治疗相比,比伐卢定联合PCI术后高剂量输注2~4h抗凝治疗可显著降低30日全因死亡率或BARC3~5型大出血的复合发生率.
中国心脏病学会基金会(CSCF2019A01),和江苏恒瑞医药的科研经费。
