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. 2025 Apr;40(4):312-319.
doi: 10.1007/s00380-024-02473-8. Epub 2024 Oct 5.

Anti-inflammatory effects of proprotein convertase subtilisin/kexin 9 inhibitor therapy in the early phase of acute myocardial infarction

Affiliations

Anti-inflammatory effects of proprotein convertase subtilisin/kexin 9 inhibitor therapy in the early phase of acute myocardial infarction

Tomohiro Shimizu et al. Heart Vessels. 2025 Apr.

Abstract

This study examined the anti-inflammatory and endothelial function-enhancing effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor therapy in the early phase after acute myocardial infarction (AMI) by assessing changes in tumor necrosis factor-α (TNF-α) levels and the L-arginine/asymmetric-dimethylarginine (ADMA) ratio. This retrospective, single-center cohort study included patients who underwent successful timely primary percutaneous coronary intervention (PCI) for first-onset AMI between September 2017 and March 2018. The PCSK9 inhibitor group comprised patients who received 75 mg alirocumab up to 7 days after AMI, while the standard therapy group comprised patients who did not. We evaluated the change in TNF-α levels and the L-arginine/ADMA ratio at the time of hospital admission and prior to discharge. PCSK9 inhibitor therapy in the early phase after AMI suppressed TNF-α levels (standard therapy group, 1.64 ± 2.14 pg/mL vs. PCSK9 inhibitor group, 0.26 ± 0.33 pg/mL; p = 0.033) and increased the L-arginine/ADMA ratio (standard therapy group, - 13.0 ± 39.7 vs. PCSK9 inhibitor group, 23.2 ± 39.7; p = 0.042). Upon multiple regression analysis adjusted for sex, age, and peak creatine kinase levels, PCSK9 inhibitor therapy was associated with TNF-α suppression (p = 0.025; β = - 0.235, 95% confidence interval [CI], - 0.436 to - 0.033). The L-arginine/ADMA ratio was also analyzed using multiple regression, adjusted for sex, age, peak creatine kinase levels, and smoking, showing a significant improvement in the ratio (p = 0.018; β = 41.913, 95% CI, 10.337-73.491). Moreover, a weak negative correlation was suggested between the change in TNF-α levels and the change in L-arginine/ADMA ratio (r = - 0.393, p = 0.058). PCSK9 inhibitor therapy in the early phase after AMI suppresses TNF-α levels and improves the L-arginine/ADMA ratio, potentially indicating anti-inflammatory and endothelial function-enhancing effects.

Keywords: l-arginine/asymmetric-dimethylarginine; Acute myocardial infarction; Proprotein convertase subtilisin/kexin 9 inhibitor; Tumor necrosis factor-α.

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Conflict of interest statement

Declarations. Conflict of interest: All authors have no commercial associations that might pose conflicts of interest in connection with this article.

Figures

Fig. 1
Fig. 1
The eligibility criteria of this study. PCSK9i, proprotein convertase subtilisin/kexin 9 inhibitor therapy; PCI, percutaneous coronary intervention; AMI, acute myocardial infarction
Fig. 2
Fig. 2
Changes in tumor necrosis factor-α (TNF-α) levels (Δ TNF-α) for both the standard therapy and PCSK9 inhibitor (PCSK9i) groups between admission and discharge. Each boxplot illustrates the interquartile range (IQR) of the changes in TNF-α levels, with the median value highlighted. Whiskers extend from the box to the furthest data points that are within 1.5 times the IQR, denoting variability outside the central 50% of the data. Points beyond the whiskers are outliers, showing extreme TNF-α changes
Fig. 3
Fig. 3
Changes in the L-arginine/asymmetric-dimethylarginine (ADMA) ratio (Δ L-arginine/ADMA ratio) for both the standard therapy and PCSK9 inhibitor (PCSK9i) groups between admission and discharge. Each boxplot illustrates the interquartile range (IQR) of the changes in TNF-α levels, with the median value highlighted. Whiskers extend from the box to the furthest data points that are within 1.5 times the IQR, denoting variability outside the central 50% of the data. Points beyond the whiskers are outliers, showing extreme L-arginine/ADMA ratio changes
Fig. 4
Fig. 4
Correlation between the change in tumor necrosis factor-α (TNF-α) levels (Δ TNF-α) and the change in L-arginine/asymmetric dimethylarginine (ADMA) ratio (Δ L-arginine/ADMA ratio). A weak negative correlation was suggested between the change in TNF-α levels and the change in L-arginine/ADMA ratio, although not statistically significant (r = − 0.393, p = 0.058)

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