在 II 期临床试验中接受 Asundexian 治疗的患者的出血结局。
Bleeding Outcomes in Patients Treated With Asundexian in Phase II Trials.
机构信息
Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Bayer AG, Wuppertal, Germany.
出版信息
J Am Coll Cardiol. 2024 Feb 13;83(6):669-678. doi: 10.1016/j.jacc.2023.12.004.
BACKGROUND
Phase II trials of asundexian were underpowered to detect important differences in bleeding.
OBJECTIVES
The goal of this study was to obtain best estimates of effects of asundexian vs active control/placebo on major and clinically relevant nonmajor (CRNM) and all bleeding, describe most common sites of bleeding, and explore association between asundexian exposure and bleeding.
METHODS
We performed a pooled analysis of 3 phase II trials of asundexian in patients with atrial fibrillation (AF), recent acute myocardial infarction (AMI), or stroke. Bleeding was defined according to the International Society on Thrombosis and Hemostasis (ISTH) criteria.
RESULTS
In patients with AF (n = 755), both asundexian 20 mg and 50 mg once daily vs apixaban had fewer major/CRNM events (3 of 249; incidence rate [IR] per 100 patient-years 5.47 vs 1 of 254 [IR: not calculable] vs 6 of 250 [IR: 11.10]) and all bleeding (12 of 249 [IR: 22.26] vs 10 of 254 [IR: 18.21] vs 26 of 250 [IR: 50.56]). In patients with recent AMI or stroke (n = 3,409), asundexian 10 mg, 20 mg, and 50 mg once daily compared with placebo had similar rates of major/CRNM events (44 of 840 [IR: 7.55] vs 42 of 843 [IR: 7.04] vs 56 of 845 [IR: 9.63] vs 41 of 851 [IR: 6.99]) and all bleeding (107 of 840 [IR: 19.57] vs 123 of 843 [IR: 22.45] vs 130 of 845 [IR: 24.19] vs 129 of 851 [IR: 23.84]). Most common sites of major/CRNM bleeding with asundexian were gastrointestinal, respiratory, urogenital, and skin. There was no significant association between asundexian exposure and major/CRNM bleeding.
CONCLUSIONS
Analyses of phase II trials involving >500 bleeds highlight the potential for improved safety of asundexian compared with apixaban and similar safety compared with placebo. Further evidence on the efficacy of asundexian awaits the results of ongoing phase III trials.
背景
asunexian 的 II 期临床试验没有足够的效力来检测出血方面的重要差异。
目的
本研究的目的是获得asunexian 与活性对照/安慰剂相比在主要和临床相关非主要（CRNM）和所有出血方面的最佳疗效估计值，描述最常见的出血部位，并探讨asunexian 暴露与出血之间的关系。
方法
我们对三项涉及心房颤动（AF）、近期急性心肌梗死（AMI）或中风的 asunexian II 期试验进行了汇总分析。出血根据国际血栓与止血学会（ISTH）标准定义。
结果
在 AF 患者（n=755）中，asunexian 20mg 和 50mg 每日一次与 apixaban 相比，主要/CRNM 事件更少（249 例中有 3 例；每 100 患者年的发生率[IR]为 5.47 例，254 例中 1 例[IR：无法计算]，250 例中 6 例[IR：11.10]）和所有出血（249 例中有 12 例[IR：22.26]，254 例中有 10 例[IR：18.21]，250 例中有 26 例[IR：50.56]）。在近期 AMI 或中风患者（n=3409）中，asunexian 10mg、20mg 和 50mg 每日一次与安慰剂相比，主要/CRNM 事件发生率相似（840 例中有 44 例[IR：7.55]，843 例中有 42 例[IR：7.04]，845 例中有 56 例[IR：9.63]，851 例中有 41 例[IR：6.99]）和所有出血（840 例中有 107 例[IR：19.57]，843 例中有 123 例[IR：22.45]，845 例中有 130 例[IR：24.19]，851 例中有 129 例[IR：23.84]）。asunexian 主要/CRNM 出血的最常见部位是胃肠道、呼吸道、泌尿生殖道和皮肤。asunexian 暴露与主要/CRNM 出血之间没有显著关联。
结论
对涉及超过 500 例出血的 II 期试验进行的分析突出了 asunexian 与 apixaban 相比安全性可能得到改善的潜力，与安慰剂相比安全性相似。正在进行的 III 期试验的结果将进一步提供 asunexian 疗效的证据。
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