ESC Congress 2026 Abstract · Oct 26, 2026

Gender-related differences in efficacy, safety and adherence of PCSK9 inhibitors in real-world clinical practice: insights from the AT-TARGET-IT Registry

By Liccardi L, Galasso G, Ciccone M et al.

Background/Introduction: Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) provide marked LDL-cholesterol (LDL-C) reduction with a favorable safety profile. Evidence from randomized trials and meta-analyses suggests reduced reduction of LDL-C in women compared to men, but real-world data on sex-related differences remain limited. Moreover, women remain persistently underrepresented in clinical trials. Purpose: AT-TARGET-IT is an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice. The purpose of this subanalysis was to investigate gender-related differences in efficacy, safety, adherence, and persistence of PCSK9i in a large real-world registry. Methods: A sex-stratified analysis of patients initiating evolocumab or alirocumab (75, 150 or 300 mg), according to ESC/EAS Guidelines indications and national reimbursement criteria, was performed. Clinical characteristics and lipid profile were collected at baseline and at subsequent follow-ups. Efficacy endpoints included LDL-C reduction and achievement of guideline-recommended LDL-C targets. Safety endpoints included patient-reported adverse events and treatment discontinuation. Adherence to therapy was also assessed. Results: A total of 2540 patients, with at least one follow-up recorded, were included in this analysis, of whom 791 (31.1%) were women. Compared with men, women were slightly older (mean age 62.7±9.5 vs 60.1±10.3 years; p<0.001) and had higher median baseline LDL-C levels (146 vs 134 mg/dL; p<0.001). After a median follow-up of 17.1 months, significantly lower LDL-C percentage reduction was observed in women compared to men (61.2% vs 66.7%, p<0.001), while absolute LDL-C reduction was similar between genders (89 mg/dL in women vs 87.4 mg/dL in men; p=0471). Consequently, women less frequently achieved LDL-C targets compared to men (54.5% vs 69.6%, p<0.001). Rates of adverse events were comparable (1.3% vs 1.4 %, p=1.0), as were discontinuation rates (5.7% vs 5.2%, p=0.645), whereas adherence to therapy was similar between genders (99% vs 98%). Conclusion(s): In a large real-world cohort, PCSK9i showed gender-related differences in LDL-C lowering, with lower relative reductions and percent of target attainment in women, despite similar absolute LDL-C reductions, comparable tolerability and adherence.

doi.org/10.1093/eurheartj/ehag785.4170 Open access Interventions