(VP101) SEX DIFFERENCES IN TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Background: Familial hypercholesteremia (FH) is the most prevalent disorder in clinical practice and is characterized by high levels of low-density lipoprotein-cholesterol (LDL-C) and premature cardiovascular disease. As an autosomal trait, FH affects equal numbers of males and females. Despite this, sex disparities in diagnosis, presentation, pharmacological therapy and lipid levels achieved have emerged worldwide, resulting in important barriers to care in FH. The objective of this study was to investigate sex-related disparities in treatment, response and guideline-recommended lipid target achievement in FH by performing a systematic review and meta-analysis of existing literature.

METHODS AND RESULTS: The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) consensus guidelines and registered in PROSPERO (CRD42022353297). We searched MEDLINE, Embase, The Cochrane library, PubMed, Scopus, and grey-literature databases. Studies were limited to English peer-reviewed literature published between database inception and April 2023. Records were eligible if they described sex differences in treatment of adults with a clinical or genetic diagnosis of heterozygous FH. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for selected outcomes using inverse variance models incorporating random-effects.

From 4981 publications reviewed, 65 met our eligibility criteria. In 16 clinical trials (1,784 participants, 47.1% females), there were no differences between sexes in response to lipid-lowering therapies (LLT), suggesting that patient sex was not a determinant of therapeutic response. In comparison, real-world evidence from registry data from 14 countries were more heterogeneous in nature. Meta-analysis of 24 studies (126,080 participants) found that females with FH were less likely to be on LLT compared to males (OR 0.76 [95% CI 0.67,0.87], p< 0.001). Similar significant trends were observed for treatment with high-intensity statins (OR 0.66 [0.57,0.76]), ezetimibe (OR 0.67 [0.57,0.78]) and PCSK9 inhibitors (OR 0.70 [0.54,0.91]). Importantly, in achievement of guideline-recommended lipid targets, females were less likely to reach an LDL-C ≤ 2.5 mmol/L (OR 0.85 [0.74,0.97], p=0.005) or a 50% reduction in LDL-C from baseline (OR 0.66 [0.55,0.80], p< 0.001). Similarly, LDL-C levels reached on treatment were higher in females, compared to males.

Conclusion: Our study found than males and females with FH show similar response to LDL-C lowering medications. Despite this, females were treated less intensively and were less likely to reach guideline recommended LDL-C targets. A better understanding of drivers of sex-related disparities in FH treatment is needed. Identifying these imbalances will allow us to reduce barriers to care and improve survival in individuals with FH.