Sex differences in LDL-C response to PCSK9 inhibitors: A real world experience

  • Martine Paquette
    Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal (Québec, Canada)
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  • Simon Faubert
    Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal (Québec, Canada)
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  • Nathalie Saint-Pierre
    Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal (Québec, Canada)
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  • Alexis Baass
    Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal (Québec, Canada)

    Department of Medicine, Divisions of Experimental Medicine and Medical Biochemistry, McGill University, Montreal (Québec, Canada)
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  • Sophie Bernard
    Corresponding author: Sophie Bernard, Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, 110 avenue des Pins Ouest, Montreal, (Québec, Canada) H2W 1R7. Phone: 1-514-987-5582, Fax: 514-987-5689
    Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal (Québec, Canada)

    Department of Medicine, Division of Endocrinology, Université de Montreal, Montreal (Québec, Canada)

    Research Centre of the Centre Hospitalier Universitaire de Montréal (CRCHUM), Montreal, (Québec, Canada)
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Published:December 07, 2022DOI:


      • The effectiveness of PCSK9 inhibition therapy in a real-world context was -66%.
      • The relative LDL-C change was significantly higher in men (-70%) than women (-59%).
      • The absolute LDL-C change was not significantly different between men and women.
      • In women, older age did not modify PCSK9 inhibitor efficacy for decreasing LDL-C.
      • With high-intensity statin, both sexes reached treatment target with PCSK9 inhibitor.



      Previous studies have shown the efficacy of PCSK9 inhibitors (PCSK9i) in lowering LDL-C. One clinical trial with alirocumab suggested that the LDL-C reduction effect is larger in men than women. In contrast, none of the studies with evolocumab have observed a difference in the treatment effect between men and women. However, sex differences data from real life experience is lacking. In addition, the difference in LDL-C response to PCSK9i between pre- and post-menopausal women has not been investigated so far.


      To compare the relative change in LDL-C following the introduction of a PCSK9i in a real-life clinical setting according to sex and menopausal status.


      All patients were recruited at the IRCM lipid clinic. Lipid profiles before and after the introduction of PCSK9i were available in the medical file for 259 patients (160 men and 99 women (72 post-menopausal, 20 pre-menopausal and 7 unknown menopausal status).


      We observed a significant difference in relative LDL-C change between men (-70%) and women (-59%), p<0.0001. However, no difference was observed between pre-menopausal (-58%) and post-menopausal (-58%) women. In a linear regression model, sex remains a significant predictor of the response to PCSK9i after correction for confounding factors such as statin intensity (beta coefficient=-0.245, p<0.0001).


      We observed a greater relative LDL-C response to PCSK9i in men than in women in a real-life clinical context. However, it is still unknown whether this difference in LDL-C change between men and women translates into a meaningful difference on long-term cardiovascular risk.


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