Heyne Sebastian, Macherey-Meyer Sascha, Meertens Max M, Finke Karl, Baldus Stephan, Adler Christoph, Lee Samuel
Faculty of Medicine, University of Cologne, University Hospital Cologne, Clinic III for Internal Medicine, Kerpener Str. 62, 50937, Cologne, Germany.
Center of Cardiology, Cardiology III - Angiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Clin Res Cardiol. 2024 Sep 16. doi: 10.1007/s00392-024-02547-7.
Left ventricular thrombus (LVT) is associated with high rates of systemic embolism. Vitamin K antagonists (VKAs) are the only approved treatment for LVT. Although evidence suggests direct oral anticoagulant (DOACs) to be at least equally effective in general, the efficacy of individual DOACs remains unclear.
A literature search was performed in EMBASE, MEDLINE and Web of Science looking for randomized controlled trials (RCTs) and non-randomized controlled studies of interventions (NRSI) comparing individual DOACs to VKAs for the treatment of LVT. Individual patient data was reconstructed and incorporated in a Bayesian network meta-analysis (NMA) and a Cox frailty regression model.
A total of 2545 patients across 19 studies (4 RCTs, 15 NRSI) were included. 1738 received VKAs, 581 received Rivaroxaban, 226 received Apixaban, 82 received Dabigatran and 2 received Edoxaban. LVT resolution was less likely with VKAs compared to Rivaroxaban in the time-to-event analysis (HR 0.66, 95% CI [0.49; 0.91], p = 0.01). There was no difference for other DOACs compared to VKAs. Rivaroxaban reduced ischemic stroke compared to VKAs (OR 0.18, 95% CrI [0.05; 0.49]), other DOACs did not.
In this NMA, Rivaroxaban showed faster LVT resolution and consecutively lower odds of ischemic stroke than VKAs while Apixaban and Dabigatran showed at least equal efficacy. Given the quality and size of the available studies, these differences between individual DOACs should be acknowledged as hypothesis generating only. Future adequately powered randomized controlled trials are needed to assess possible time-varying effects between individual DOACs.
左心室血栓(LVT)与较高的全身栓塞发生率相关。维生素K拮抗剂(VKAs)是唯一被批准用于治疗LVT的药物。尽管有证据表明直接口服抗凝剂(DOACs)总体上至少同样有效,但个别DOACs的疗效仍不明确。
在EMBASE、MEDLINE和Web of Science中进行文献检索,寻找比较个别DOACs与VKAs治疗LVT的随机对照试验(RCTs)和非随机对照干预研究(NRSI)。重建个体患者数据并纳入贝叶斯网络荟萃分析(NMA)和Cox脆弱性回归模型。
共纳入19项研究(4项RCTs,15项NRSI)中的2545例患者。1738例接受VKAs治疗,581例接受利伐沙班治疗,226例接受阿哌沙班治疗,82例接受达比加群治疗,2例接受依度沙班治疗。在事件发生时间分析中,与利伐沙班相比,VKAs治疗时LVT溶解的可能性较小(HR 0.66,95%CI[0.49;0.91],p = 0.01)。与VKAs相比,其他DOACs无差异。与VKAs相比,利伐沙班可降低缺血性卒中的发生率(OR 0.18,95%CrI[0.05;0.49]),其他DOACs则不能。
在本NMA中,利伐沙班显示出比VKAs更快的LVT溶解速度,缺血性卒中的发生率也更低,而阿哌沙班和达比加群显示出至少相同的疗效。鉴于现有研究的质量和规模,个别DOACs之间的这些差异仅应被视为产生假设。未来需要进行足够有说服力的随机对照试验,以评估个别DOACs之间可能的时间变化效应。