Sex X Time Interactions in Lp(a) and LDL-C Response to Evolocumab
Open accessAbstract
The aim of this study was to evaluate whether there were significant sex x time interactions in lipoprotein(a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C) response to treatment with the Proprotein Convertase Subtilisin/Kexin type 9 inhibitor (PCSK9i) Evolocumab, in a real-life clinical setting. For this purpose, we pooled data from 176 outpatients (Men: 93; Women: 83) clinically evaluated at baseline and every six months after starting Evolocumab. Individuals who had been on PCSK9i for less than 30 months and nonadherent patients were excluded from the analysis. Over time, absolute values of Lp(a) plasma concentrations significantly decreased in the entire cohort (p-value < 0.001) and by sex (p-value < 0.001 in men and p-value = 0.002 in and women). However, there were no sex-related significant differences. Absolute plasma concentrations of LDL-C significantly decreased over time in the entire cohort and by sex (p-value < 0.001 always), with greater improvements in men compared to women. The sex x time interaction was statistically significant in LDL-C (all p-values < 0.05), while absolute changes in Lp(a) were not influenced by either sex or time (all p-value > 0.05). Our data partially reinforce the presence of differences in response to treatment to PCSK9i between men and women and are essential to gain a better understanding of the relationship between LDL-C and Lp(a) lowering in response to PCSK9i. Further research will clarify whether these sex-related significant differences translate into a meaningful difference in the long-term risk of ASCVD.
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PCSK9 inhibitors produce a median reduction in Lp(a) percentage, but this reduction does not translate into a decrease in cardiovascular events.
“Clinical trials have shown a median reduction in Lp(a) percentage with PCSK9 inhibitors, but this reduction does not translate into a decrease in cardiovascular events [14,15].”
From Residual Cardiovascular Risk: Role of Remnants Cholesterol, Monocyte/HDL Ratio and Lipoprotein Ratios on Personalized Cardiovascular Prevention (2024) · cites this paper as [15]
The Introduction reports percentage reductions in Lp(a) with PCSK9 inhibitors, but gives mean differences rather than a median reduction. The Discussion says forthcoming cardiovascular outcome trials will clarify whether lowering Lp(a) improves outcomes; it does not establish that the reduction fails to decrease cardiovascular events. The study registered no major cardiovascular events during follow-up, which cannot establish a lack of benefit. (LLM, conf=0.88)
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“Clinical trials have shown a median reduction in Lp(a) percentage with PCSK9 inhibitors, but this reduction does not translate into a decrease in cardiovascular events [14,15].”
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- Authors
- Fogacci, F., Yerlitaş, S. İ., Giovannini, M., Zararsız, G., Lido, P., Borghi, C., & Cicero, A. F. G.
- Affiliations
- University of Bologna (IT)
- Erciyes University (TR)
- Italian Medicines Agency (IT)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Corresponding author
- Cicero, Arrigo F. G.
- ORCID
- Venue
- Biomedicines
- Publisher
- MDPI AG
- Published
- 2023-12-11
- Volume
- 11
- Issue
- 12
- Pages
- 3271
- ISSN
- 2227-9059 (ISSN-L)
- PMC
- PMC10741148
- OpenAlex
- W4389574430
- Cited by
- 15
- References
- 44
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 1
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Agenzia Italiana del Farmaco, Ministero della Salute
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- evolocumab, PCSK9 inhibitors, lipoprotein(a), LDL cholesterol, sex differences, treatment response, hypercholesterolemia, atherosclerotic cardiovascular disease risk
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