Despite Similar Treatment Effects, Women with FH Less Likely to Receive Treatment or Meet Goals

Iulia Iatan, MD, PhD
Credit: X.com

In what investigators are calling the largest study of its kind to date on the topic, new research indicates females with familial hypercholesterolemia (FH) receive suboptimal care relative to their male counterparts.

Despite clinical trial data evidencing a similar magnitude of benefit from medications, results of the systematic review, which included data from more than 120,000 patients, suggest women were less likely to be treated intensively and to reach LDL-C target goals than their male counterparts.¹

“A deeper 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,” wrote investigators.¹

Although the field has undergone historic advancement since the turn of the century, optimal management of lipid disorders remains a goal rather than a standard for lipidologists and cardiology as a whole—evidenced by the plateauing rates of reduction in deaths related to atherosclerotic cardiovascular disease. In the current study, a team of investigators led by Iulia Iatan, MD, PhD, a physician-scientist in the Centre for Heart Lung Innovation at the University of British Columbia, sought to assess the comparative effects of lipid-lowering therapies as well as disparities in real-world management.^1,2

With this in mind, the systematic review included a search from inception through April 26, 2023 of the MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases for studies pertaining to sex differences in the treatment of adults with FH. Per study design, investigators planned a pair of qualitative analyses assessing sex differences in the treatment of FH and sex differences in cardiovascular disease outcomes in treated FH, respectively, as well as a pair of quantitative meta-analyses assessing each of the aforementioned topics. For inclusion, studies needed to be interventional or observational in nature, conducted among adult populations with heterozygous FH diagnosed using genetic and/ or common clinical criteria, and report data separately for male and female participants.¹

The investigators' initial search yielded 5838 records. Of these, 4432 underwent screening and 133 were included in the qualitative synthesis. In total, 52 studies on sex differences in treatment of FH and 81 studies on sex differences in cardiovascular outcomes in treated FH were included in the review.¹

Among 1840 participants from 16 interventional clinical trials, including 8 randomized trials, there were no differences observed for response to fixed doses of lipid-lowering therapy between males and females. In a meta-analysis of 25-real-world observational studies with more than 129,000 participants, results indicated female patients were 26% less likely to be on lipid-lowering therapy than their male counterparts (Odds Ratio [OR], 0.74; 95% CI, 0.66 to 0.95).¹

Further analysis demonstrated female patients were also less likely to reach an LDL-C less than 2.5 mmol/L (OR, 0.85; 95% CI, 0.74 to 0.97). However, data from a meta-analysis of 57 studies reporting differences in cardiovascular outcomes suggested male patients experienced a more than doubling in the rate of cardiovascular events than female patients (Risk Ratio, 2.16; 95% CI, 1.89 to 2.47).¹

Investigators pointed to several limitations in their study to consider when interpreting the results. These limitations included but were not limited to, the possibility relevant reports were omitted despite the search efforts, studies reported significant associations between sex and cardiovascular outcomes might be more likely to be published, the possibility that the trim-and-fill method may not be valid in the presence of excess heterogeneity between studies, and an inability to account for gender identity and important aspects of intersectionality.¹

“These results emphasize the importance of considering sex in risk-stratifying patients with FH and highlight the need for sex-specific strategies for [cardiovascular disease] prevention,” investigators wrote.¹

References:

1. Iatan I, Akioyamen LE, Ruel I, et al. Sex differences in treatment of familial hypercholesterolaemia: a meta-analysis. Eur Heart J. Published online July 8, 2024. doi:10.1093/eurheartj/ehae417
2. Case BC, Waksman R. Coronary Heart Disease: Have We Reached a Plateau in Primary Prevention?. J Am Heart Assoc. 2020;9(7):e04963. doi:10.1161/JAHA.120.016034