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. 2023 Oct 28;2(9):100669.
doi: 10.1016/j.jacadv.2023.100669. eCollection 2023 Nov.

Sex Differences in Cardiovascular Outcomes and Cholesterol-Lowering Efficacy of PCSK9 Inhibitors: Systematic Review and Meta-Analysis

Frederick Berro Rivera  1 , Sung Whoy Cha  2 , John Paul Aparece  3 , Aubrey Rocimo  4 , Bradley Ashley Ong  4 , Jem Marie Golbin  4 , Pia Gabrielle Alfonso  4 , Byambaa Enkhmaa  5 , Safi U Khan  6 , Miguel Cainzos-Achirica  7 , Annabelle Santos Volgman  8 , Ann Marie Navar  9 , Nishant P Shah  10
Affiliations

Sex Differences in Cardiovascular Outcomes and Cholesterol-Lowering Efficacy of PCSK9 Inhibitors: Systematic Review and Meta-Analysis

Frederick Berro Rivera et al. JACC Adv. .

Abstract

Background: Guideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i) monoclonal antibodies can help further reduce LDL-C and major adverse cardiovascular events (MACE) although differences in efficacy by sex and type are less understood.

Objectives: The authors sought to determine if there are differences in the efficacy of LDL-C lowering and reduction in the risk of MACE by sex and type of PCSK9i.

Methods: A comprehensive literature search was done through October 17, 2022, for published trials comparing PCSK9i vs control. Outcomes assessed were LDL-C reduction and incidence of MACE following the use of PCSK9i vs placebo, stratified by sex and type of PCSK9i used.

Results: We identified 16 trials with 54,996 adults, and 15,143 (27.5%) of them were female. PCSK9i significantly reduced MACE compared to placebo in both women (HR: 0.86, 95% CI: 0.74-0.97, P < 0.001) and men (HR: 0.85, 95% CI: 0.79-0.91, P < 0.001) with no significant sex difference (MD -0.01, 95% CI: -0.14 to -0.13, P = 0.930). PCSK9i also significantly reduced LDL-C levels in both sexes at 12 weeks (females: MD -62.57, 95% CI: -70.24 to -54.91, P < 0.001; males: MD -66.19, 95% CI: -72.03 to -60.34, P < 0.001) and 24 weeks (females: MD -47.52, 95% CI: -52.94 to -42.09, P < 0.001; males: MD -54.07, 95% CI: -59.46 to -48.68, P < 0.001). Significant sex difference was seen in the LDL reduction of PCSK9i for both 12 weeks (males vs females: MD -4.55, 95% CI: -7.34 to -1.75, P < 0.01) and 24 weeks (males vs females: MD -7.11, 95% CI: -9.99 to -4.23, P < 0.001).

Conclusions: The use of PCSK9i results in significant LDL-C and MACE reduction in both males and females. While there is no significant sex difference in MACE reduction, LDL-C reduction is greater in males than in females. Our data support the equal use of PCSK9i in all eligible patients, regardless of sex.

Keywords: PCSK9 inhibitors; cardiovascular events; sex difference; tertiary prevention.

PubMed Disclaimer

Conflict of interest statement

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
PCSK9 Inhibitor vs Placebo (A) LDL-C reduction in females after 12 weeks of therapy; (B) LDL-C reduction in males after 12 weeks of therapy; (C) sex difference in LDL-C reduction after 12 weeks of therapy. LDL-C = low-density lipoprotein cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type-9.
Figure 2
Figure 2
PCSK9 Inhibitor vs Placebo (A) LDL-C reduction in females after 24 weeks of therapy; (B) LDL-C reduction in males after 24 weeks of therapy; (C) sex difference in LDL-C reduction after 24 weeks of therapy.
Figure 3
Figure 3
PCSK9 Inhibitor vs Placebo (A) Major adverse cardiovascular events (MACE) in females; (B) MACE in males; (C) sex difference in MACE.
Figure 4
Figure 4
PCSK9 Inhibitor vs Ezetimibe (A) LDL-C reduction in females after 24 weeks of therapy; (B) LDL-C reduction in males after 24 weeks of therapy; (C) sex difference in LDL-C reduction after 24 weeks of therapy.
Figure 5
Figure 5
PCSK9 Inhibitor vs Placebo (A) LDL-C reduction in females after 24 weeks of therapy, by type of PCSK9 inhibitor; (B) LDL-C reduction in males after 24 weeks of therapy, by type of PCSK9 inhibitor; (C) sex difference in LDL-C reduction after 24 weeks of therapy, by type of PCSK9 inhibitor.
Figure 5
Figure 5
PCSK9 Inhibitor vs Placebo (A) LDL-C reduction in females after 24 weeks of therapy, by type of PCSK9 inhibitor; (B) LDL-C reduction in males after 24 weeks of therapy, by type of PCSK9 inhibitor; (C) sex difference in LDL-C reduction after 24 weeks of therapy, by type of PCSK9 inhibitor.
Central Illustration
Central Illustration
Sex Difference on Cardiovascular Outcomes of PCSK9 Inhibitors A total of 54,996 participants from 16 trials were included in the study. Main outcomes include incidence of MACE and mean LDL-C reduction of PCSK9i vs placebo stratified by sex. LDL-C = low-density lipoprotein cholesterol; MACE = major adverse cardiovascular event; PCSK9i = proprotein convertase subtilisin/kexin type-9 inhibitor; RCT = randomized controlled trial.
See this image and copyright information in PMC

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