Revisiting the Efficacy and Safety of Bivalirudin in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Insights From a Mixed Treatment Comparison Meta-Analysis of Randomized Trials.

Randomized trials of bivalirudin in patients with ST elevation myocardial infarction (STEMI) have yielded heterogeneous results. Our aim was to evaluate the efficacy and safety of four antithrombin regimens-unfractionated heparin (UFH), bivalirudin (stopped soon after percutaneous coronary intervention [PCI]), extended bivalirudin (continued for a few hours after PCI), and combined UFH and a Gp2b3a inhibitors (GPI) in patients who present with STEMI. A PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized clinical trials (RCTs) of the above antithrombin in patients with STEMI. The primary outcome was net adverse cardiovascular events (NACE). The primary ischemic endpoint was major adverse cardiovascular events (MACE), and the primary safety endpoint was major bleeding, and other endpoints included all-cause mortality and stent thrombosis. The primary analysis compared the effect of these antithrombin regimens in reference to UFH using a mixed treatment comparison meta-analysis. In the 14 RCTs evaluating 25,415 patients with STEMI, when compared to UFH monotherapy, extended bivalirudin lowered NACE (OR = 0.71 with 95% CI: 0.53-0.96; moderate level of confidence) driven by a significant decrease in major bleeding (OR = 0.42 with 95% CI: 0.26-0.68; high level of confidence) without any significant difference in MACE or all-cause mortality. When compared with UFH monotherapy, UFH+GPI reduced risk of MACE (OR = 0.76 with 95% CI: 0.60-0.97; high level of confidence) but at the expense of an increase in major bleeding (OR = 1.48 with 95% CI: 1.11-1.98; high level of confidence) with no difference in NACE or all-cause mortality. For major bleeding, extended bivalirudin infusion ranked #1, bivalirudin ranked #2, UFH monotherapy ranked #3, and combined UFH and GPI ranked #4. For NACE, extended bivalirudin infusion ranked #1, bivalirudin ranked #2, combined UFH and GPI ranked #3, and UFH monotherapy ranked #4. Cluster plots for MACE and major bleeding demonstrated that extended bivalirudin had the best balance for efficacy and safety. In patients undergoing PCI for STEMI, extended bivalirudin offers the best balance for primary ischemic (MACE) and safety (major bleeding) outcomes.

Maqsood MH ，Tamis-Holland JE ，Feit F ，Bangalore S ... -  《-》

Bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment: pooled analysis from the ACUITY and ISAR-REACT

Ndrepepa G ，Neumann FJ ，Deliargyris EN ，Mehran R ，Mehilli J ，Ferenc M ，Schulz S ，Schömig A ，Kastrati A ，Stone GW ... -  《-》

Bivalirudin versus heparin in patients with or without bail-out GPI use: a pre-specified subgroup analysis from the BRIGHT-4 trial.

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; Pinteraction = 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.

Liao J ，Qiu M ，Feng X ，Chen K ，Zhang D ，Zou Y ，Zheng X ，Zhao G ，Tian N ，Zheng Z ，Peng X ，Yang Q ，Liang Z ，Li Y ，Han Y ，Stone GW ... -  《BMC Medicine》

Reduced-dose of bivalirudin (without the post-procedure infusion) in patients with acute coronary syndrome undergoing elective percutaneous coronary intervention.

In clinical practice, the dose of bivalirudin may not be fully applicable to the Chinese population. Therefore, this study aimed to explore the efficacy and safety of a reduced dose (80% of the recommended dose) of bivalirudin without post-procedure infusion for 3-4 h in patients with acute coronary syndrome (ACS) undergoing elective percutaneous coronary intervention (PCI). This was a single-center, retrospective study. Patients who met the inclusion criteria and no exclusion criteria were divided into reduced-dose and recommended-dose groups for analysis. Confounders were corrected using propensity score matching. The incidence of net adverse clinical events (NACE), major adverse cardiovascular events (MACE), and Bleeding Academic Research Consortium (BARC) type 2-5 bleeding events were observed 30 days postoperatively. In total, 1,590 patients (795 per group) were obtained after propensity score matching. The results after propensity score matching were as follows: The activated clotting time (ACT) after 5 min in the reduced-dose group was 349.37 ± 47.59 s, which was statistically lower than that in the recommended-dose group, 353.12 ± 44.98 s (P = 0.024). There was no significant difference in the proportion of ACT values of ≥ 250 s after 5 min between the two groups (P > 0.05). There were no significant differences in NACE, MACE, and BARC type 2-5 bleeding events between the two groups (5.0% vs. 4.5%, P = 0.638; 0.0% vs. 0.1%, P = 1.000; 0.3% vs. 0.5%, P = 0.687). There were no statistically significant differences in cumulative NACE and cumulative bleeding events between the two groups at 30 days (P = 0.635 and P = 0.716, respectively). In patients with UA and NSTEMI undergoing elective PCI, 80% of the recommended dose of bivalirudin without post-procedure infusion can be used for anticoagulation without increasing the risk of thrombosis and bleeding.

Wang Q ，Liu Y ，Yang L ，Zhou T ，Zhang Q ，Zhang Z ，Sun D ，Wang X ... -  《BMC Cardiovascular Disorders》

Heparin and Bivalirudin in Percutaneous Coronary Intervention for Acute Coronary Syndromes: A Review Article.

Acute coronary syndrome (ACS) is one of the most common leading global causes of mortality, encompassing ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA). Percutaneous coronary intervention (PCI) has become a pivotal therapeutic approach for ACS, underscoring the importance of anticoagulation strategies. Among the commonly employed anticoagulants in PCI, heparin and bivalirudin take precedence, with heparin serving as the archetypal choice. Nevertheless, the determination of an optimal anticoagulation regimen remains a point of contention in contemporary clinical practice. To address the differences in anticoagulants during PCI, we meticulously conducted a literature review through PubMed and Web of Science, employing search terms such as "heparin," "bivalirudin," "percutaneous coronary intervention," and "acute coronary syndrome." For patients with PIC brought on by STEMI, NSTEMI, and stable or UA pectoris, the review focused on randomized controlled trials to assess and compare the efficacy and safety of heparin and bivalirudin as anticoagulant options. This systematic review is aimed at furnishing valuable insights into the ongoing debate surrounding the choice of anticoagulation regimens in PCI. By scrutinizing clinical evidence derived from relevant trials, we seek to inform and guide healthcare practitioners in making informed decisions based on the unique requirements of patients with various ACS presentations.

Wang G ，Qi K ，Li X ，Zuo S ，Zhang R ，Zhao Y ，Sun S ，Zhang J ，Liu X ... -  《-》