PMID- 34971394 OWN - NLM STAT- MEDLINE DCOM- 20220509 LR - 20220902 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 29 IP - 5 DP - 2022 May 5 TI - Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study. PG - 832-841 LID - 10.1093/eurjpc/zwab229 [doi] AB - AIMS: Lomitapide is a lipid-lowering agent indicated as an adjunct therapy for adult homozygous familial hypercholesterolaemia (HoFH). This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe. METHODS AND RESULTS: In a multicentre retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, low-density lipoprotein cholesterol (LDL-C) changes, adverse events (AEs), and major adverse cardiovascular events (MACE) were assessed. After a median 19 months (interquartile range 11-41 months) of treatment with a mean dosage of 20 mg of lomitapide. Low-density lipoprotein cholesterol decreased by 60%, from baseline 280.5 mg/dL (191.8-405.0 mg/dL) to 121.6 mg/dL (61.0-190.5 mg/dL). At the last visit, 32.0% of patients achieved LDL-C <100 mg/dL and 18.7% <70 mg/dL. At baseline, 38 HoFH patients were receiving LDL apheresis (LA), but after initiation of lomitapide 36.8% of patients discontinued LA. During follow-up, lomitapide was permanently interrupted in 13% of patients. Gastrointestinal AEs occurred in 40% and liver transaminases increased (3-5 x upper limits of normal) in 13% of patients. Among patients with liver ultrasound evaluation (n = 45), a modest increase in hepatic steatosis was noted during treatment; however, liver stiffness measured by elastography in 30 of them remained within the normal range. Among HoFH patients exposed to lomitapide for at least 2 years, MACE incident rate was 7.4 per 1000 person-years in the 2 years after as compared to 21.2 per 1000 person-years before treatment with lomitapide. CONCLUSION: In this medium-term real-world experience, lomitapide proved to be very effective in reducing LDL-C in HoFH. Gastrointestinal AEs were common, but liver safety was reassuring with no sign of increased risk of liver fibrosis. A signal of cardiovascular protection was also observed. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - D'Erasmo, Laura AU - D'Erasmo L AUID- ORCID: 0000-0002-9174-4667 AD - Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Universita 35, 00161, Rome, Italy. FAU - Steward, Kim AU - Steward K AD - Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. FAU - Cefalu, Angelo Baldassare AU - Cefalu AB AD - Dipartimento di Promozione Della Salute Materno Infantile, Medicina Interna e Specialistica Di Eccellenza "G. D'Alessandro" (PROMISE), Universita degli Studi di Palermo, Via del Vespro 129, 90127 Palermo, Italy. FAU - Di Costanzo, Alessia AU - Di Costanzo A AD - Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Universita 35, 00161, Rome, Italy. FAU - Boersma, Eric AU - Boersma E AUID- ORCID: 0000-0002-2559-7128 AD - Department of Cardiology, Erasmus MC, University Medical Centre Rotterdam, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. FAU - Bini, Simone AU - Bini S AD - Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Universita 35, 00161, Rome, Italy. FAU - Arca, Marcello AU - Arca M AD - Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Universita 35, 00161, Rome, Italy. FAU - van Lennep, Jeanine Roeters AU - van Lennep JR AD - Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. CN - Italian and European Working Group on Lomitapide in HoFH LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 0 (Anticholesteremic Agents) RN - 0 (BMS201038) RN - 0 (Benzimidazoles) RN - 0 (Cholesterol, LDL) SB - IM CIN - Eur J Prev Cardiol. 2022 May 5;29(5):829-831. PMID: 35148370 EIN - Eur J Prev Cardiol. 2022 Oct 18;29(13):1812. PMID: 36053228 MH - Adult MH - *Anticholesteremic Agents/adverse effects MH - Benzimidazoles MH - Cholesterol, LDL MH - Homozygote MH - *Homozygous Familial Hypercholesterolemia MH - Humans MH - *Hyperlipoproteinemia Type II/diagnosis/drug therapy MH - Retrospective Studies OTO - NOTNLM OT - Atherosclerosis OT - Homozygous familial hypercholesterolaemia OT - Lomitapide OT - Medium-term efficacy OT - Medium-term safety FIR - D'Erasmo, Laura IR - D'Erasmo L FIR - Cefalu, Angelo Baldassare IR - Cefalu AB FIR - Di Costanzo, Alessia IR - Di Costanzo A FIR - Bini, Simone IR - Bini S FIR - Giammanco, Antonina IR - Giammanco A FIR - Averna, Maurizio IR - Averna M FIR - Iannuzzo, Gabriella IR - Iannuzzo G FIR - Fortunato, Giuliana IR - Fortunato G FIR - Gentile, Marco IR - Gentile M FIR - Puja, Arturo IR - Puja A FIR - Montalcini, Tiziana IR - Montalcini T FIR - Pavanello, Chiara IR - Pavanello C FIR - Calabresi, Laura IR - Calabresi L FIR - Vigna, Giovanni Battista IR - Vigna GB FIR - Bucci, Marco IR - Bucci M FIR - Bonomo, Katia IR - Bonomo K FIR - Nota, Fabio IR - Nota F FIR - Sampietro, Tiziana IR - Sampietro T FIR - Sbrana, Francesco IR - Sbrana F FIR - Suppressa, Patrizia IR - Suppressa P FIR - Sabba, Carlo IR - Sabba C FIR - Fimiani, Fabio IR - Fimiani F FIR - Cesaro, Arturo IR - Cesaro A FIR - Calabro, Paolo IR - Calabro P FIR - Ventura, Fulvio IR - Ventura F FIR - D'Addato, Sergio IR - D'Addato S FIR - Pisciotta, Livia IR - Pisciotta L FIR - Bertolini, Stefano IR - Bertolini S FIR - Arca, Marcello IR - Arca M FIR - Kolovou, Genovefa IR - Kolovou G FIR - Liberopoulos, Evangelos IR - Liberopoulos E FIR - Daphnis, Eugene IR - Daphnis E FIR - van Lennep, Jeanine Roeters IR - van Lennep JR FIR - Rutten, Joost IR - Rutten J FIR - Boersma, Eric IR - Boersma E FIR - Steward, Kim IR - Steward K FIR - Vogt, Anja IR - Vogt A FIR - Cegla, Jaimini IR - Cegla J FIR - Walji, Shahenaz IR - Walji S FIR - Kayikcioglu, Meral IR - Kayikcioglu M FIR - Real, Jose IR - Real J FIR - Martinez-Hervas, Sergio IR - Martinez-Hervas S FIR - Ellis, Avishay IR - Ellis A FIR - Littmann, Karin IR - Littmann K EDAT- 2022/01/01 06:00 MHDA- 2022/05/10 06:00 CRDT- 2021/12/31 12:10 PHST- 2021/11/25 00:00 [received] PHST- 2021/12/18 00:00 [revised] PHST- 2021/12/27 00:00 [accepted] PHST- 2022/01/01 06:00 [pubmed] PHST- 2022/05/10 06:00 [medline] PHST- 2021/12/31 12:10 [entrez] AID - 6491248 [pii] AID - 10.1093/eurjpc/zwab229 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2022 May 5;29(5):832-841. doi: 10.1093/eurjpc/zwab229.