Comparative Efficacy and Safety of Limus-Eluting Stents in Acute Coronary Syndrome in Asian People: A Network Meta-Analysis and Bioinformatics Study

• Marista Prazeva

  Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

• Adha Hendrawan

  Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

• Farhan Habiby

  Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

Introduction: Evidence on the relative performance of limus-eluting stents (LES) in acute coronary syndrome (ACS) among Asian patients is mixed, and formal rankings with biological context are limited. We compared LES and examined drug-specific mechanisms. Methods: Randomized trials of ACS patients undergoing PCI with 12-month outcomes were identified systematically. A frequentist network meta-analysis combined 19 trials (n=25,642) to estimate odds ratios (ORs) for major adverse cardiovascular events (MACE) and mortality and to derive treatment ranks (P-scores). Bioinformatics included molecular docking to FKBP12/mTOR/VEGFR2, ADMET/toxicity prediction, protein–protein interaction networks, and KEGG/GO enrichment. Results and Discussion: All limus stents lowered 12-month MACE versus paclitaxel (ZES 0.46 [0.34–0.64]; EES 0.55 [0.41–0.71]; SES 0.58 [0.46–0.72]; BES 0.60 [0.42–0.86]). Differences within the limus class were small (ZES vs SES 0.80 [0.62–1.06]). Rankings favored zotarolimus (SUCRA 0.94), followed by everolimus (0.64) and sirolimus (0.50); biolimus (0.42) ranked below, and paclitaxel was lowest. Mortality did not differ. Docking indicated stronger binding of limus agents to FKBP12/mTORC1 than paclitaxel, and toxicity models suggested a wider safety margin for limus agents (everolimus LD50 2,500 mg/kg; paclitaxel 134 mg/kg). Enrichment analyses highlighted PI3K–Akt/mTOR pathways relevant to vascular healing. Conclusion: In Asian ACS, LES outperform paclitaxel at 12 months. Zotarolimus ranks first, with everolimus and sirolimus performing comparably. The clinical ranking aligns with predicted target engagement and toxicity profiles.

Copyright (c) 2025 Marista Prazeva, Adha Hendrawan, Farhan Habiby

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