No sex differences in lipid-lowering effect and treatment benefit of PCSK9 inhibitors

The use of PCSK9 inhibitors in both primary and secondary prevention has been associated with a reduced risk of major adverse cardiovascular events (MACE), non-fatal myocardial infarction (MI), and stroke. According to a new meta-analysis, this effect is similar for men and women; however, the low-density lipoprotein-cholesterol (LDL-C) lowering effect seems to be smaller in women.

PCSK9 inhibitors can reduce LDL-C, even in patients that cannot reach ideal LDL-C target levels with high-dose statin and ezetimibe. They have also been shown to reduce MACE [1]. However, it remained unclear whether potential sex differences in LDL-C reduction existed. Dr Frederick Rivera (Lincoln Medical Center, NY, USA) and colleagues hence performed a comprehensive literature search, identifying ongoing studies using ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform [2]. Included in the meta-analysis were 16 trials that passed the inclusion criteria.

Adverse cardiovascular outcomes were significantly reduced by PCSK9 inhibitor use versus placebo in both men (HR 0.85; 95% CI 0.80–0.91; P<0.0001) and women (HR 0.86; 95% CI 0.76–0.96; P=0.009). The significant reductions in LDL-C that were found with PCSK9 inhibitors compared with placebo and ezetimibe were similar for both sexes. A significant reduction in LDL-C was seen in both sexes when analysed according to the frequency of PCSK9 inhibitor administration (i.e. biweekly or monthly) and the type of PCSK9 inhibitor (i.e. evolocumab or alirocumab).

“We conclude that there is no sex difference regarding adverse cardiovascular events and LDL-C reduction among PCSK9 inhibitors. However, subgroup analysis shows greater LDL-C-lowering in men compared with women,” Dr Rivera said.

1. 
   
   1. Du H, et al. Heart 2019;105(15):1149–1159.
   2. Rivera FB, et al. Sex Differences on cardiovascular outcomes of Pcsk9-inhibitors: A meta-analysis. GR.APS.P201, AHA Scientific Sessions 2022, 05–07 November, Chicago, USA.

 

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Posted on 11 January, 202322 February, 2024