Available online 8 December 2022

Author links open overlay panelAbstractBackground

: Previous studies have shown the efficacy of PCSK9 inhibitors (PCSK9i) in lowering LDL-C. One clinical trial with alirocumab suggested that the LDL-C reduction effect is larger in men than women. In contrast, none of the studies with evolocumab have observed a difference in the treatment effect between men and women. However, sex differences data from real life experience is lacking. In addition, the difference in LDL-C response to PCSK9i between pre- and post-menopausal women has not been investigated so far.

Objectives

: To compare the relative change in LDL-C following the introduction of a PCSK9i in a real-life clinical setting according to sex and menopausal status.

Methods

: All patients were recruited at the IRCM lipid clinic. Lipid profiles before and after the introduction of PCSK9i were available in the medical file for 259 patients (160 men and 99 women (72 post-menopausal, 20 pre-menopausal and 7 unknown menopausal status).

Results

: We observed a significant difference in relative LDL-C change between men (-70%) and women (-59%), p<0.0001. However, no difference was observed between pre-menopausal (-58%) and post-menopausal (-58%) women. In a linear regression model, sex remains a significant predictor of the response to PCSK9i after correction for confounding factors such as statin intensity (beta coefficient=-0.245, p<0.0001).

Conclusion

: We observed a greater relative LDL-C response to PCSK9i in men than in women in a real-life clinical context. However, it is still unknown whether this difference in LDL-C change between men and women translates into a meaningful difference on long-term cardiovascular risk.

Section snippetsINTRODUCTION

Low-density lipoprotein cholesterol (LDL-C) is a well-established and important cardiovascular risk factor. HMG-CoA reductase inhibitor (statin) therapy is the first line of lipid-lowering treatment for atherosclerotic cardiovascular disease (ASCVD) risk reduction.1, 2, 3 In the IMPROVE-IT trial, the addition of ezetimibe to statin therapy has also demonstrated a significant, if modest, additional clinical benefit on ASCVD risk reduction.4 However, residual CV risk remains a major concern.

Study Population and Data Collection

We conducted a retrospective analysis using data from patients followed at the lipid clinic of the Montreal Clinical Research Institute (IRCM) between 2016 and 2021. Patients were eligible for inclusion in this study if they were aged ≥ 18 years and had been treated with a PCSK9 monoclonal antibody (evolocumab or alirocumab 75mg or 150mg) for at least 8 weeks. Patients with missing LDL-C data (before PCSK9 inhibitor or on-treatment) or those with unstable lipid-lowering therapy regimen (e.g.:

Baseline characteristics

Baseline characteristics of study subjects according to sex are presented in Table 1. A total of 99 women and 160 men are included. Diastolic blood pressure and body mass index were significantly lower in women than in men (-3 mmHg and -1.2 kg/m2, respectively), whereas baseline values of total cholesterol (+0.62 mmol/L), LDL-C (+0.34 mmol/L), HDL-C (+0.32 mmol/L), and non-HDL-C (+0.19 mmol/L) were all significantly higher. History of ASCVD before the introduction of a PCSK9 inhibitor was less

DISCUSSION

In this study, we investigated the LDL-C response to PCSK9 inhibitors in a real-life clinical context, leading to four main key findings. First, the average LDL-C reduction in the whole cohort (-2.46 mmol/L (-66%)) is as high as expected from the clinical trial studies (∼ -60%). Second, men have a significantly greater relative LDL-C reduction following PCSK9 inhibitors than women, independently of the background LLT regimen. Although the absolute LDL-C change (in mmol/L) was not significantly

CONCLUSIONS

We presented a single-center study showing a real-world effectiveness of PCSK9 inhibition therapy that is comparable to the LDL-C response reported in clinical trials. However, we observed that the relative response, but not the absolute change, is significantly greater in men than in women, independently of confounding factors such as the background LLT regimen. Furthermore, we demonstrated for the first time that there is no difference in the relative LDL-C response to PCSK9 inhibitors

CONTRIBUTORS’ STATEMENT

Conceptualization: S.B. (lead), S.F. (supporting)

Supervision: S.B. (lead), M.P. (supporting)

Data collection: N. S-P. (lead), S.F. (lead) and M.P. (supporting)

Data curation: M.P.

Formal analysis: M.P.

Project administration: M.P.

Analysis and interpretation of data: All authors

Writing - Original Draft: M.P.

Writing - Review & Editing: All authors

Final approval of the version to be published: All authors

Agreement to act as guarantor of the work: All authors

Dr. Bernard had full access to all the data

Declaration of Competing Interest

A.B. received research grants from Akcea, Amgen, Astra Zeneca, Fondation Leducq, Fondation Yvan Morin, Merck Frosst and Sanofi. He has participated in clinical research protocols from Acasti Pharma Inc., Akcea, Amgen, Astra Zeneca, Ionis Pharmaceuticals, Inc., The Medicines Company, Merck Frosst, Novartis, Pfizer, Regeneron Pharmaceuticals Inc. and Sanofi. He has served on advisory boards and received honoraria for symposia from Akcea, Amgen and Sanofi. S.B. received research grants from Akcea,

ACKNOWLEDGEMENTS

The authors want to thank the Montreal Clinical Research Institute research team and the nursing staff for their everyday help, support, and implication.

FUNDING SOURCES

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

DATA AVAILABILITY

The data underlying this article will be shared on reasonable request to the corresponding author.

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© 2022 Published by Elsevier Inc. on behalf of National Lipid Association.