# PCSK9-Targeting Drugs and Gender: Are There Any Differences?

## TL;DR

This study finds that women may respond more slowly to PCSK9-targeting cholesterol drugs compared to men, suggesting a need for personalized treatment approaches.

## Contribution

The study provides new evidence on sex-specific differences in LDL-C target attainment and response to PCSK9-targeted therapies.

## Key findings

- Women had a lower prevalence of previous cardiovascular events but were more likely to be classified as high cardiovascular risk.
- Fewer women achieved LDL-C targets at the first two follow-up visits compared to men.
- Women showed smaller LDL-C reductions at the first follow-up despite similar treatment tolerance.

## Abstract

Background: Atherosclerotic cardiovascular disease (ASCVD) is often perceived as a male-dominant condition, yet recent European data show that more women live with and die from it. Gender disparities have been reported in the management of dyslipidemia, with women less likely to receive high-intensity lipid-lowering therapy and to reach low-density lipoprotein cholesterol (LDL-C) goals. This study aimed to assess sex-specific differences in response to and tolerance of PCSK9-targeted therapies—monoclonal antibodies (evolocumab, alirocumab) and small interfering RNA (inclisiran)—as well as LDL-C goal attainment according to current ESC guidelines. Methods: We conducted a prospective registry of patients initiating PCSK9-targeted therapy at a specialized lipid center between April 2018 and June 2024. Baseline lipid profiles were recorded and monitored over follow-up. Results: Of the 341 patients, 122 (35.8%) were women and 219 (64.2%) were men, with a mean age of 66.4 ± 12.6 years for the women and 63.9 ± 11.8 years for the men. The women more frequently had heterozygous familial hypercholesterolemia (HeFH) (61.5% vs. 38.4%, p < 0.001) and a lower prevalence of previous cardiovascular events compared to the men (62.3% vs. 84.5%, p < 0.001). A higher proportion of the women were classified as high cardiovascular risk compared to the men (37.7% vs. 15.5%, p < 0.001). Risk categories were assigned according to ESC guidelines, with LDL-C targets of <70 mg/dL for high-risk patients and <55 mg/dL for very high risk patients, along with a ≥50% LDL-C reduction for both categories. In the very high risk group, fewer women achieved LDL-C targets at the first two follow-up visits (first follow-up: 50.0% vs. 76.6%, p = 0.008; second follow-up: 55.3% vs. 68.1%, p = 0.049). Although treatment prescription and tolerance were similar between sexes, women showed smaller LDL-C reductions at the first follow-up (51.7 ± 23.9% vs. 57.3 ± 24.9%, p = 0.044). Conclusions: PCSK9-targeted therapies were effective in both sexes at third follow-up, although women showed a tendency toward a delayed response and lower target attainment, indicating the potential need for more personalized management strategies.