State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiology, General Hospital of Northern Theater Command, Cardiovascular Research Institute, Shenyang, 110016, China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
BMC Med. 2024 Sep 27;22(1):410. doi: 10.1186/s12916-024-03579-6.
Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use.
We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2-4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days.
A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13-2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20-2.52; P = 0.004) but not in the risk of BARC types 3-5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31-2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39-0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41-0.83; P = 0.003), and BARC types 3-5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06-0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36-1.66; P = 0.50; P = 0.07) or its individual components between bivalirudin and heparin groups.
Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3-5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI.
ClinicalTrials.gov NCT03822975.
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，比较比伐卢定与肝素抗凝的结果存在争议，部分原因是糖蛋白 IIb/IIIa 抑制剂（GPI）的混杂作用。本研究旨在比较比伐卢定加 PCI 后高剂量输注与肝素加或不加 bailout GPI 治疗的安全性和有效性。
我们对 BRIGHT-4 试验进行了预先指定的亚组分析，该试验将 6016 例 STEMI 患者随机分为接受比伐卢定加 PCI 后 2-4 小时高剂量输注或肝素单药治疗的两组。仅将 GPI 保留为程序性血栓并发症的 bailout 治疗。主要结局为 30 天内全因死亡或 Bleeding Academic Research Consortium（BARC）3-5 型出血的复合结局。
共有 5250（87.4%）例患者未使用 GPI 接受治疗，758（12.6%）例患者使用 bailout GPI。与未使用 GPI 相比，使用 bailout GPI 与主要结局的风险增加相关（5.28%比 3.41%；调整后的危险比（aHR），1.62；95%置信区间（CI），1.13-2.33；P=0.009）和全因死亡（5.01%比 3.12%；aHR，1.74；95%CI，1.20-2.52；P=0.004），但与 BARC 3-5 型出血（0.53%比 0.48%；aHR，0.90；95%CI，0.31-2.66；P=0.85）无关。在未使用 GPI 的患者中，比伐卢定与较低的主要结局发生率相关（2.63%比 4.21%；aHR，0.55；95%CI，0.39-0.77；P=0.0005）、全因死亡（2.52%比 3.74%；aHR，0.58；95%CI，0.41-0.83；P=0.003）和 BARC 3-5 型出血（0.15%比 0.81%；aHR，0.19；95%CI，0.06-0.57；P=0.003）相比肝素。然而，在需要 bailout GPI 的患者中，比伐卢定和肝素组之间主要结局（5.76%比 4.87%；aHR，0.77；95%CI，0.36-1.66；P=0.50；P=0.07）或其各个组成部分的发生率无显著差异。
在未使用 GPI 的 STEMI 患者中，与肝素单药治疗相比，比伐卢定加 PCI 后高剂量输注与显著降低 30 天全因死亡或 BARC 3-5 型出血的复合发生率相关。然而，由于在 PCI 期间发生血栓并发症，在需要 bailout GPI 的患者中，这些益处可能不太明显。
ClinicalTrials.gov NCT03822975。
