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Inhibitors of apolipoprotein C3, triglyceride levels, and risk of pancreatitis: a systematic review and meta-analysis

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Abstract

In recent years, novel apoC3 inhibitor therapies for the treatment of hypertriglyceridemia have been developed and assessed through phase II and III clinical trials. The objective of this study was to perform an updated meta-analysis on the impact of new apoC3 inhibitor drugs on triglyceride and apoC3 levels, as well as on the incidence of pancreatitis. We conducted a meta-analysis of randomized, placebo-controlled studies assessing the effects of apoC3 inhibitors therapy (antisense oligonucleotides and small interfering RNA) on triglyceride levels, apoC3 levels, and the occurrence of acute pancreatitis. This meta-analysis was performed according to PRISMA guidelines. The random-effects model was performed. Nine randomized clinical trials (n = 717 patients) were considered eligible for this systematic review. ApoC3 inhibitor drugs were consistently associated with decreased triglyceride levels (MD -57.0%; 95% CI -61.9 to -52.1, I2 82%) and lowered apoC3 values (MD -76; 95% CI -80.1 to -71.8, I2 77%) when compared to placebo. Furthermore, the use of apoC3 inhibitor drugs demonstrated a reduction in the risk of acute pancreatitis (OR 0.11; 95% CI 0.04 to 0.27, I2 0%). The present updated meta-analysis of randomized clinical trials demonstrated that the utilization of apoC3 inhibitors in patients with hypertriglyceridemia correlated with reduced apoC3 and triglyceride levels, along with a decreased risk of acute pancreatitis compared to the placebo.

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Data availability

The data underlying this article are available in the article and in the supplementary material.

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Authors and Affiliations

  1. Department of Cardiology, Hospital Italiano de Buenos Aires, Peron 4190, Buenos Aires, C1199ABB, Argentina

    Walter Masson, Leandro Barbagelata & Daniel Siniawski

  2. Department of Cardiology, Hospital Militar Campo de Mayo, Buenos Aires, Argentina

    Martín Lobo

  3. Endocrinology, Nutrition and Metabolism Research Center, Faculty of Health Sciences, Universidad Nacional de Formosa, Formosa, Argentina

    Juan P. Nogueira

  4. International University of the Americas, San José, Costa Rica

    Juan P. Nogueira

  5. Faculty of Medicine, Fasta University, Mar del Plata, Argentina

    Pablo Corral

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Contributions

WM and JPN participated in the conception and design of the research. WM, JPN and PC participated in the data collection. The interpretation of the data and the statistical analysis was done by WM and ML. WM, LB, PC, and JPN drafted the manuscript. All authors performed a critical review of the final document. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Walter Masson.

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This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.

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WM, JPN and PC have served as a speaker from PTC therapeutics. The rest of the authors have no conflicts to declare.

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Masson, W., Lobo, M., Nogueira, J.P. et al. Inhibitors of apolipoprotein C3, triglyceride levels, and risk of pancreatitis: a systematic review and meta-analysis. Rev Endocr Metab Disord (2024). https://doi.org/10.1007/s11154-024-09893-x

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