PCSK9 inhibitors revisited: Effectiveness and safety of PCSK9 inhibitors in a real-life Spanish cohort

Introduction: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have emerged as a therapeutic option for patients with hypercholesterolemia who do not attain low-density lipoprotein cholesterol (LDL-C) goals and/or are intolerant to other lipid-lowering drugs. Our aim was to analyze the effectiveness and safety of PCSK9i in routine clinical practice and factors related to poor outcomes. Materials and methods: We conducted an ambispective study in 115 patients who recieved alirocumab or evo-locumab, in a tertiary level hospital. From February 2017 to April 2020, patients were recruited and followed up for a median of 20.4 months. The main outcomes were relative reduction in LDL-C, percentage of patients achieving the therapeutic goals established by 2016 ESC/EAS guidelines, incidence of major cardiovascular events (MACEs) and drug-related adverse events (ADRs). Results: The median LDL-C achieved was 57.0 mg/dL (relative reduction of 59.9% from baseline, p< 0.001). After adjusting for confounders, smaller LDL-C reductions were related to female sex, absence of concomitant lipid-lowering therapy and treatment with alirocumab. Overall, 84.6% of the patients achieved the therapeutic goals. During follow-up, 7 MACEs were detected. ADRs, generally considered mild, affected 38.1% of the participants (mainly mialgias and arthralgias) and triggered discontinuations in 8.7% of cases. Conclusions: PCSK9i are effective and safe, although certain factors may influence their effectiveness. Interest-ingly, our results suggest that alirocumab and evolocumab may not be therapeutic equivalents, as initially suggested.

Automated summary

PCSK9 inhibitors have shown to be effective and safe in treating patients with hypercholesterolemia, with factors such as female sex, lack of concomitant lipid-lowering therapy, and treatment with alirocumab potentially influencing their effectiveness. The study found that 84.6% of patients achieved therapeutic goals, with drug-related adverse events affecting a portion of participants.