ArticleAnnals of medicine and surgery (2012)2026
Inflammation-modulating agents in chronic limb-threatening ischemia: a narrative review of therapeutic potential and future directions.
Article in Annals of medicine and surgery (2012), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease (PAD), driven by both advanced atherosclerosis and chronic inflammation. Despite advancements in revascularization and medical therapy, outcomes remain poor. Inflammation has emerged as a key therapeutic target, and several anti-inflammatory agents are under investigation for potential benefit in CLTI. A comprehensive literature review was conducted using PubMed, Scopus, Embase, Google Scholar, and Web of Science to identify studies published between 1990 and 2025. Keywords included "chronic limb-threatening ischemia," "peripheral artery disease," "colchicine," "canakinumab," "methotrexate," "NLRP3 inflammasome," and "anti-inflammatory therapy." Eligible studies included original research, clinical trials, systematic reviews, and relevant guidelines focused on inflammation-targeted interventions in atherosclerosis and limb ischemia. Colchicine has shown significant reductions in major adverse cardiovascular events in large trials and retrospective PAD studies, though no randomized controlled trials (RCTs) have specifically addressed CLTI. Canakinumab reduced inflammatory biomarkers and improved walking performance in PAD but had no effect on plaque progression. Methotrexate did not demonstrate cardiovascular benefit in the Cardiovascular Inflammation Reduction Trial. Preclinical agents targeting the NLRP3 inflammasome (e.g., MCC950) have shown anti-inflammatory effects but lack human data. Nutraceuticals, including omega-3 fatty acids and polyphenols, may offer adjunctive benefits, though evidence remains limited. Inflammation-modulating therapies hold promise as adjuncts in CLTI management, potentially improving outcomes by targeting the underlying immune mechanisms of disease progression. However, current evidence is insufficient for clinical adoption in CLTI. Large-scale, well-designed RCTs focusing on limb-specific outcomes are necessary to clarify the role of these therapies in high-risk vascular populations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.