Sex Differences in Low-Density Lipoprotein Cholesterol Reduction With PCSK9 Inhibitors in Real-world Patients: The LIPID-REAL Registry

Abstract

Background:Previous evidence supports that monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 50%–65%, regardless of baseline treatments. We tested possible sex differences in a multicentre registry of real-world patients treated with PCSK9 inhibitors.Methods:This is a multicentre and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 18 different hospitals. Before-treatment and on-treatment LDLc and medical treatments, clinical indication, and clinical features were recorded.Results:Women represented 24.69% of the cohort. The use of statins was similar in both sexes, but women were receiving most frequently ezetimibe. Before-treatment median LDLc was 135 (interquartile range 115–166) mg, and it was higher in women. The median on-treatment LDLc was 57 (interquartile range 38–84) mg/dL, which represented a mean 54.5% reduction. On-treatment LDLc was higher in women, and the mean LDLc reduction was lower in women (47.4% vs. 56.9%; P = 0.0002) receiving evolocumab or alirocumab. The percentage of patients who achieved ≥50% LDLc reduction was higher in men (71.36% vs. 57.62%; P = 0.002). According to LDLc before-treatment quartiles, LDLc reduction was statistically lower in women in the 2 highest and a significant interaction of women and baseline LDLc >135 mg/dL was observed. Women were negatively associated with lower rates of LDLc treatment target achievement (odds ratio: 0.31). Differences were also observed in women with body mas index >25 kg/m2. Only 14 patients (2.14%) presented side effects.Conclusions:This multicentre and retrospective registry of real-world patients treated with PCSK9 inhibitors highlights significant gender differences in LDLc reduction.

Women with familial hypercholesterolemia phenotype are undertreated and poorly controlled compared to men

“…Recent data have shown similar cardiovascular benefits in both sexes using plasma proprotein convertase subtilisin/kexin type 9 inhibitors (iPCSK9) 23 , although the LIPID-REAL Registry 24 has shown lower LDL-c reduction in women in the 2 highest quartiles. Nevertheless, the study on the use of iPCSK9 in Catalonia (Spain) from the Catalan Department of Health observed that women only received 41% of a total of 1.917 provided treatments 25 .…”

Effect of PCSK9 inhibitors on remnant cholesterol and lipid residual risk: The LIPID‐REAL registry

“…This is an investigator-initiated study of patients treated with PCSK9 inhibitors under local criteria. 14,15 It is a multicenter and retrospective study designed to assess the efficacy of PCS9 inhibitors treatment on LDLc reduction in real-world patients. Investigators were invited to participate and share their results using a simple database designed by the study and investigators from 18 different Spanish hospitals finally agreed to participate; all were included in the public national health system.…”

“…This is an investigator‐initiated study of patients treated with PCSK9 inhibitors under local criteria 14,15 . It is a multicenter and retrospective study designed to assess the efficacy of PCS9 inhibitors treatment on LDLc reduction in real‐world patients.…”

Current challenges in the diagnosis and management of acute coronary syndromes in women

“…As for PCSK9 inhibitors, data from the FOURIER trial demonstrated that inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL-C levels in all subgroups with no sex differences [84]. However, only one multicenter registry investigated sex-related differences in PCSK9 inhibitors' efficacy [85]. The study demonstrated that women had substantially higher LDL-C levels and a lower LDL-C reduction compared with men (47.4% vs. 56.9%; P = 0.0002) [85].…”

“…However, only one multicenter registry investigated sex-related differences in PCSK9 inhibitors' efficacy [85]. The study demonstrated that women had substantially higher LDL-C levels and a lower LDL-C reduction compared with men (47.4% vs. 56.9%; P = 0.0002) [85].…”