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

Area of Science:

• Cardiology
• Pharmacology
• Genetics

Background:

• Atherosclerotic cardiovascular disease (ASCVD) affects more women than perceived, with existing gender disparities in dyslipidemia management.
• Women are less likely to receive intensive lipid-lowering therapies and achieve low-density lipoprotein cholesterol (LDL-C) goals.
• PCSK9-targeted therapies offer a novel approach to managing dyslipidemia.

Purpose of the Study:

• To evaluate sex-specific differences in response to PCSK9-targeted therapies (monoclonal antibodies and siRNA).
• To assess LDL-C goal attainment and treatment tolerance between men and women.
• To identify potential needs for personalized management strategies in women.

Main Methods:

• Prospective registry of 341 patients initiating PCSK9-targeted therapy.
• Analysis of baseline and follow-up lipid profiles, including LDL-C levels.
• Comparison of treatment response, goal attainment, and tolerance between sexes based on ESC guidelines.

Main Results:

• Women (35.8%) more frequently had heterozygous familial hypercholesterolemia (HeFH) and were classified as high cardiovascular risk.
• Fewer women achieved LDL-C targets in the very high-risk group at early follow-ups.
• Women showed smaller LDL-C reductions at first follow-up, despite similar treatment tolerance.

Conclusions:

• PCSK9-targeted therapies are effective in both sexes by the third follow-up.
• Women may experience a delayed response and lower initial LDL-C goal attainment.
• Personalized management strategies may enhance lipid-lowering efficacy in women.