LDL lowering effect of PCSK9 inhibition is reduced in women - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Heart Journal - Cardiovascular Pharmacotherapy Année : 2023

LDL lowering effect of PCSK9 inhibition is reduced in women

Résumé

Abstract Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma low-density lipoprotein cholesterol (LDL-C) concentration, and its inhibition reduces the risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the sex-differential effect of either pharmacological or genetic inhibition of PCSK9 on LDL-C levels. Methods and results We meta-analyzed six real-life studies (1216 men and 641 women) that investigated the effects of PCSK9 monoclonal antibodies (mAbs) on LDL-C reduction in men and women. Despite higher LDL-C levels in women at baseline [mean difference (MD) = 17.4 mg/dL, P < 0.0001, women = 175 mg/dL vs. men = 152 mg/dL], the LDL-C reduction under PCSK9 mAb treatment was significantly greater in men (MD = 7.6 mg/dL, 95% confidence interval: 2.7–12.4, P = 0.002) than in women. We tested the sex-related association of the loss-of-function variant PCSK9-R46L with LDL-C plasma levels in 382 813 individuals (219 301 women and 163 512 men) free of lipid-lowering drugs from the UK Biobank general population cohort. The magnitude of LDL-C reduction was larger in men than in women (mean LDL-C difference: –35 mg/dL vs. –26 mg/dL, when comparing homozygous carriers with non-carriers in men and women, respectively). The relationship between PCSK9-R46L and LDL-C was significantly dependent on sex (P for interaction = 7.2e–04). Conclusion These results demonstrate by complementary approaches that the decrease in LDL-C mediated by PCSK9 inhibition is slightly, but significantly, less marked in women than in men. These data reinforce the need for specific studies to develop sex-specific recommendations for the management of ASCVD in women.

Dates et versions

hal-04212334 , version 1 (20-09-2023)

Identifiants

Citer

Veronika Myasoedova, Antoine Rimbert, Marina Camera, Cedric Le May, Romain Capoulade, et al.. LDL lowering effect of PCSK9 inhibition is reduced in women. European Heart Journal - Cardiovascular Pharmacotherapy, 2023, 9 (4), pp.337-342. ⟨10.1093/ehjcvp/pvad009⟩. ⟨hal-04212334⟩
9 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More