Carmine De Luca (1), Luigi Junior Valletta (1), Guido D'Errico (1), Raffaele Russo (1), Gabriella Iannuzzo (1), Matteo Di Minno (1), Ilenia Lorenza Calcaterra (1)

(1) Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli, Federico II.

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Background and aim: Bempedoic acid, an ATP citrate lyase inhibitor, is indicated for patients with hypercholesterolemia who are statin-intolerant or inadequately controlled by standard therapy. Although randomized trials demonstrated efficacy, evidence from real-world, genetically characterized cohorts remains limited.

Methods: We perfomed a prospective cohort study. Familial hypercholesterolemia (FH) patients with a stable treatment (>6 month) with PCSK9i mAbs were included. Group1 was switched to treatment with PCSK9i siRNA (inclisiran) and Group2 continued the treatment with PCSK9i mAbs (Alirocumab or Evolocumab). Lipid profile [total cholesterol (TC) and LDL-C] and % of LDL-C target achievement were evaluated at the baseline (T0) and at 6-months follow-up (T1).

Results: 52 FH patients were enrolled. Group1 (n=26) 56% males, average age of 56.1±14.8years; 50% in secondary prevention. At T0, TC was 179.6±67.5mg/dl, LDL-C was 105.7±62.2mg/dl. At T1, TC was 175.4±53.1 mg/dl and LDL-C value was 97.6±47.9 mg/dl. Group2 (n=26) 42% males, average age of 61.5±12.4years; 46% in secondary prevention. At T0, TC was 139.8±54.8 mg/dl, LDL-C was 65.8±51.0mg/dl. At T1, TC was 137.6±35.0mg/dl and LDL-C was 63.1±32.2mg/dl. No significant difference between T1-T0 LDL-C Δ mean % reduction was found comparing the 2 groups (10% for Group1 vs 35% for Group2 p=0,260). No significant difference in % of target achievement at T1 was found (31% for Group 1 and 50% for Group 2; OR: 95%CI:36.4-61.9, p=0.131).

Conclusions: Our preliminary results showed that no significant difference in efficacy were found between treatment with PCSK9i mAbs and siRNA, confirming siRNA a promising option mainly in low-adherent patients.