Antibody-mediated LOX-1 inhibition in patients with residual inflammation after myocardial infarction: a randomized phase 2 trial
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10505587" target="_blank" >RIV/00179906:_____/25:10505587 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/25:10505587
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=u_Y3QhlF4G" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=u_Y3QhlF4G</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41591-025-03951-w" target="_blank" >10.1038/s41591-025-03951-w</a>
Alternative languages
Result language
angličtina
Original language name
Antibody-mediated LOX-1 inhibition in patients with residual inflammation after myocardial infarction: a randomized phase 2 trial
Original language description
The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is a key scavenger receptor for oxidized low-density lipoprotein cholesterol (oxLDL), which promotes inflammation and atherosclerosis. Here we evaluated MEDI6570, an antibody that acts as a LOX-1 antagonist, in a randomized, double-blind, dose-finding study in patients with myocardial infarction (MI) and residual inflammation (high-sensitivity C-reactive protein >= 1 mg l(-1)). At 30-365 days after MI, 423 patients (75 women, 348 men) were randomly allocated to 50 mg, 150 mg or 400 mg MEDI6570 or placebo treatment subcutaneously every 4 weeks for 32 weeks. The primary endpoint, the change in the noncalcified plaque volume in the most diseased coronary segment (NCPVMD) by computed tomography angiography, was not significantly different between placebo and MEDI6570 at any dose. The secondary endpoints, global NCPV and low-attenuation plaque volume, were also not different between placebo and MEDI6570 at any dose (all placebo-adjusted comparisons, P > 0.05). With regard to exploratory endpoints, there were reductions in free soluble LOX-1 (sLOX-1) from baseline by 44.8%, 85.8%, 94.0% and 96.4% in the placebo, 50 mg, 150 mg and 400 mg dose arms, respectively (all placebo-adjusted comparisons P < 0.001). Interleukin-6 (IL-6) levels decreased by 2.9%, -3.0%, 18.9% and 21.5% in the placebo, 50 mg, 150 mg and 400 mg arms, respectively, with substantial placebo-adjusted reductions observed only at 150 mg and 400 mg (P < 0.05). MEDI6570 was well tolerated and rates of serious adverse events were similar in the MEDI6570 and placebo groups. In summary, despite favorable effects on sLOX-1 and IL-6, a LOX-1 inhibitor did not reduce noncalcified coronary plaque volume in patients with residual inflammation after acute MI. EudraCT registration: 2020-000840-75.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Medicine
ISSN
1078-8956
e-ISSN
1546-170X
Volume of the periodical
31
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
nestránkováno
UT code for WoS article
001580834800001
EID of the result in the Scopus database
2-s2.0-105018118439