Efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors in patients with extremely high lipoprotein(a) levels >180 mg/dL

Aim . To evaluate the efficacy of proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitor therapy in patients with extremely high lipoprotein(a) (Lp(a)) levels >180 mg/dL. Material and methods . This retrospective analysis of electronic health records of patients with documented Lp(a) levels >180 mg/dL. Patients were recruited from a large sample of 101 078 individuals who had undergone Lp(a) assessment. Absolute and relative changes in Lp(a) and low-density lipoprotein (LDL) cholesterol (C) levels compared to baseline were assessed during PCSK9 inhibitor therapy. Results . A total of 1105 patients were included. The mean age was 52,7±14,6 years. The median was 53 years. Median baseline Lp(a) was 198 mg/dl, and LDL-C was 4,31±1,18 mmol/l; 12,9% received PCSK9 inhibitors. With PCSK9 therapy, the decrease in Lp(a) level was -29,03 vs -10,28% without PCSK9 inhibitor therapy (p<0,001), the decrease in LDL-C level was -44,83% (p<0,001). The most pronounced effect was noted with the triple combination (statin + ezetimibe + PCSK9 inhibitor) as follows: Lp(a) by -30,31%, LDL-C by -46,79% (p<0,001). A decrease in Lp(a) level was associated with higher baseline Lp(a) (β=0,195; p<0,001) and age (β=0,176; p=0,021). The addition of any PCSK9 inhibitor was associated with a reduction in Lp(a) levels (β=7,764; p=0,002). Conclusion . In patients with Lp(a) levels >180 mg/dL, PCSK9 inhibitors not only lower LDL-C but also reduce Lp(a) in real-world settings. These results highlight the potential of PCSK9 inhibitors as a key component of therapy for patients with extremely high Lp(a) levels prior to the widespread adoption of Lp(a)-targeted agents.