Effect of intravenous methotrexate carried by lipid nanoemulsion in patients with anterior ST-elevation myocardial infarction

IF 2.5 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

IJC Heart and Vasculature Pub Date : 2025-08-13 DOI:10.1016/j.ijcha.2025.101771

Aline G. Ferrari , Raul C. Maranhão , Rocío Salsoso , Vanessa M.G.T.F. Baldo , Remo H.M. Furtado , Talia F. Dalçóquio , Carlos A.K. Nakashima , Luciano M. Baracioli , Felipe G. Lima , Aleksandra T. Morikawa , Gabriela Liberato , Carlos E. Rochitte , Cesar H. Nomura , Roberto Kalil Filho , Paul M. Ridker , Robert P. Giugliano , Marc S. Sabatine , Thauany M. Tavoni , Roberto R.C.V. Giraldez , José C. Nicolau

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引用次数: 0

Abstract

Background

Inflammation plays a central role in the pathophysiology of ST-elevation myocardial infarction (STEMI), being associated with larger infarct size (IS) and worse left ventricular remodeling (LVR). Methotrexate (MTX) is a potent anti-inflammatory drug with potential benefits in the treatment of STEMI. Experimental studies have suggested that a formulation of MTX incorporated into lipid nanoemulsion (LDE-MTX) could be beneficial and safe.

Objectives

To evaluate the efficacy and safety of LDE-MTX in patients with STEMI.

Methods

Randomized, double-blinded, placebo-controlled, proof-of-concept study. Patients were randomized 4 ± 2 days after first anterior STEMI to receive LDE-MTX (40 mg/m² intravenous infusion) or LDE-placebo weekly for 6 weeks. The primary efficacy endpoint was left ventricle end-diastolic volume (LVEDV) assessed by cardiac magnetic resonance at 90 ± 7 days post-randomization; the main secondary endpoints were changes in LVEDV, other LVR parameters and IS.

Results

Due to the COVID-19 pandemic the study was stopped prematurely, with 32 randomized patients (15 LDE-placebo, 17 LDE-MTX) completing the protocol. At 90 days, there was no difference in LVEDV between groups. Among other secondary endpoints, there appeared to be a greater reduction of IS (%LV) in favor of the LDE-MTX group (−3.9 ± 6.9 vs −9.4 ± 8.4, p = 0.030). LDE-MTX was well tolerated.

Conclusions

In patients with STEMI, LDE-MTX appears to be safe but did not influence LVEDV and other LVR parameters, although it possibly reduced infarct size at 90 days. These hypothesis-generating results support further investigation of a novel nanomedicine approach to STEMI in larger trials.

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脂质纳米乳携带甲氨蝶呤静脉注射对st段抬高型心肌梗死患者的影响

背景：炎症在st段抬高型心肌梗死（STEMI）的病理生理学中起着核心作用，与较大的梗死面积（IS）和更严重的左心室重构（LVR）相关。甲氨蝶呤（MTX）是一种有效的抗炎药物，在治疗STEMI中具有潜在的益处。实验研究表明，将MTX掺入脂质纳米乳（LDE-MTX）可能是有益和安全的。目的评价LDE-MTX治疗STEMI患者的疗效和安全性。方法随机、双盲、安慰剂对照、概念验证研究。患者在首次前路STEMI后4±2天随机接受LDE-MTX （40mg /m2静脉输注）或lde -安慰剂，每周接受6周。主要疗效终点是随机分组后90±7天通过心脏磁共振评估的左心室舒张末期容积（LVEDV）；主要次要终点为LVEDV、其他LVR参数和IS的变化。由于COVID-19大流行，研究提前停止，32名随机患者（15名lde -安慰剂，17名LDE-MTX）完成了方案。在第90天，两组之间的LVEDV没有差异。在其他次要终点中，LDE-MTX组似乎有更大的IS （%LV）降低（- 3.9±6.9 vs - 9.4±8.4,p = 0.030）。LDE-MTX耐受性良好。结论在STEMI患者中，LDE-MTX似乎是安全的，但不影响LVEDV和其他LVR参数，尽管它可能降低了90天的梗死面积。这些产生假设的结果支持在更大规模的试验中进一步研究一种新的纳米药物治疗STEMI的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

IJC Heart and Vasculature Medicine-Cardiology and Cardiovascular Medicine

CiteScore

4.90

自引率

10.30%

发文量

216

审稿时长

56 days

期刊介绍： IJC Heart & Vasculature is an online-only, open-access journal dedicated to publishing original articles and reviews (also Editorials and Letters to the Editor) which report on structural and functional cardiovascular pathology, with an emphasis on imaging and disease pathophysiology. Articles must be authentic, educational, clinically relevant, and original in their content and scientific approach. IJC Heart & Vasculature requires the highest standards of scientific integrity in order to promote reliable, reproducible and verifiable research findings. All authors are advised to consult the Principles of Ethical Publishing in the International Journal of Cardiology before submitting a manuscript. Submission of a manuscript to this journal gives the publisher the right to publish that paper if it is accepted. Manuscripts may be edited to improve clarity and expression.