Division of Cardiology (D.-W.P., J.-M.A., D.-Y.K., S.-A.L., E.K., D.-H.K., S.-J.P.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Asan Image Metrics, Clinical Trial Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea (K.W.K.).
Circulation. 2022 Aug 9;146(6):466-479. doi: 10.1161/CIRCULATIONAHA.122.059512. Epub 2022 Apr 4.
It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear.
We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement.
A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; =0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function.
In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research.
URL: https://www.
gov. Unique identifier: NCT03284827.
经导管主动脉瓣置换术后，直接口服抗凝剂依度沙班能否降低瓣叶血栓形成及随之而来的脑血栓栓塞风险尚不清楚。此外，亚临床瓣叶血栓形成与脑栓塞以及神经或认知功能障碍之间的因果关系仍不清楚。
我们开展了一项多中心、开放性标签随机试验，比较了依度沙班与双联抗血小板治疗（阿司匹林加氯吡格雷）在成功行经导管主动脉瓣置换术且无抗凝指征的患者中的疗效。主要终点是 6 个月时 4 维 CT 显示瓣叶血栓形成的发生率。关键次要终点是脑磁共振成像上新的脑病灶数量和体积以及 6 个月内和经导管主动脉瓣置换术后即刻神经和认知功能的连续变化。
共有 229 例患者纳入最终意向治疗人群。依度沙班组瓣叶血栓形成的发生率较双联抗血小板治疗组有降低趋势（9.8%比 18.4%；绝对差值为-8.5%[95%CI，-17.8%至 0.8%]；=0.076）。脑磁共振成像上新出现脑病灶的患者比例（依度沙班组比双联抗血小板治疗组，25.0%比 20.2%；差值为 4.8%；95%CI，-6.4%至 16.0%）和两组间的中位数新病灶总数和体积均无差异。此外，两组间神经和认知功能恶化的患者比例也无差异。两组间任何部位或主要出血事件的发生率也无差异。我们发现瓣叶血栓形成的存在或严重程度与新的脑病变和神经或认知功能变化之间无显著关联。
在成功行经导管主动脉瓣置换术后无长期抗凝指征的患者中，依度沙班治疗组瓣叶血栓形成的发生率较双联抗血小板治疗组有降低趋势，但无统计学意义。两组间新发脑血栓栓塞和神经或认知功能的影响也无差异。由于该研究的效力不足，研究结果应被视为假说生成，突出了进一步研究的必要性。
NCT03284827。
