Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry
Authors: D’Erasmo Laura , Bini Simone , Casula Manuela , Gazzotti Marta , Bertolini Stefano , Calandra Sebastiano , Tarugi Patrizia , Averna Maurizio , Iannuzzo Gabriella , Fortunato Giuliana , Catapano Alberico L , Arca Marcello ,   LIPIGEN HoFH group, Allevi Massimiliano , Auricchio Renata , Banderali Giuseppe , Baratta Francesco , Bartuli Andrea , Bianconi Vanessa , Bonomo Katia , Brambilla Marta , Branchi Adriana , Bruzzi Patrizia , Bucci Marco , Buonuomo Paola Sabrina , Calabrò Paolo , Carrubbi Francesca , Cavalot Franco , Cipollone Francesco , D’Addato Sergio , Dal Pino Beatrice , Del Ben Maria , Di Costanzo Alessia , Di Taranto Maria Donata , Fasano Tommaso , Ferri Claudio , Fimiani Fabio , Fogacci Federica , Formisano Elena , Galimberti Federica , Giammanco Antonina , Grigore Liliana , Iughetti Lorenzo , Mandraffino Giuseppe , Mombelli Giuliana , Montalcini Tiziana , Muntoni Sandro , Nascimbeni Fabio , Negri Emanuele A , Notargiacomo Serena , Noto Davide , Passaro Angelina , Pavanello Chiara , Pecchioli Valerio , Pecchioli Lorenzo , Pederiva Cristina , Pellegatta Fabio , Piras Cristina , Piro Salvatore , Pirro Matteo , Pisciotta Livia , Pujia Arturo , Rinaldi Elisabetta , Rizzi Luigi , Sanz Juana Maria , Sarzani Riccardo , Sbrana Francesco , Scicali Roberto , Suppressa Patrizia , Toscano Arianna , Tramontano Daniele , Vigna Giovanni B , Werba Josè Pablo , Zambon Sabina , Zambon Alberto , Zenti Maria Grazia 
Published: February 2024

Abstract

Aims
The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting.

Methods and results
The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt &lt; 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016).

Conclusion
Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH.