CONGRESS ABSTRACT

Background: Research has indicated a gender disparity in dyslipidemia management, with women being significantly more likely to fail to meet LDL-C targets and less likely to receive high-intensity lipid-lowering medications in response to elevated LDL-C levels. The aim of this analysis was to highlight potential gender differences in response to and tolerance of novel drugs targeting PCSK9. Population and Methods: Between April 2018 and June 2024, patients who accessed to a second-level centre for the treatment of dyslipidaemias to begin PCSK9mAb (monoclonal antibodies) and Inclisiran therapy were included in a prospective registry. Our cohort consisted of 341 patients: 122 (35.8%) were women, mean age was 64.83 ± 12.11 years. Among them, 80 (23.5%) were at high cardiovascular risk, and 261 (76.5%) were at very high cardiovascular risk. Results: In our population, women were more frequently affected by heterozygous familial hypercholesterolemia (HeFH) (p<0,001) and, compared to men, had a lower frequency of cardiovascular events (p<0,001), resulting in a higher proportion being classified as high cardiovascular risk (p<0,001). Among patients with very high cardiovascular risk, women demonstrated a lower rate of achieving LDL-C targets (p=0,010). This discrepancy is likely attributed to the higher prevalence of familial hypercholesterolemia (p=0.048) and consequently to the higher baseline LDL-C levels among very high CV risk women. We did not observe gender differences in the prescription of first- and second-line lipid-lowering medications or in tolerance to therapies, and no absolute differences in response to PCSK9-targeted therapy were noted. Conclusions: In our analysis, no gender differences were observed in terms of efficacy and tolerance to the new PCSK9 inhibitors. The observed difference in target achievement within our cohort is attributed to the higher percentage of women with heterozygous familial hypercholesterolemia (HeFH) who have extremely poorly controlled LDL-C levels. In contrast, male patients, possibly due to heightened awareness of cardiovascular risk and recurrence—both in the general population and among healthcare professionals—appear to present at our center with better-controlled LDL-C levels, even following a cardiovascular event. This finding is consistent with other studies indicating that women, particularly those with familial hypercholesterolemia, are diagnosed later and undertreated compared to men.