Management of children with heterozygous familial hypercholesterolaemia worldwide: a meta-analysis
Year: 2024
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: Aims Heterozygous familial hypercholesterolaemia (HeFH) is one of the most frequent monogenic disorders in the world, leading to premature atherosclerotic cardiovascular diseases. The aim of this meta-analysis was to evaluate the efficacy and safety of lipid-lowering therapy (LLT) and achievement of low density lipoprotein cholesterol (LDL-C) goal in children with HeFH. Methods and results The main endpoint was efficacy of goal achievement for LDL-C and other lipid parameters: total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), apolipoprotein B, and lipoprotein(a), and the LLT safety [adverse events (AEs), including endocrine function, and growth indices]. The secondary endpoint was an effect of LLT on attainment of LDL-C goal treatment (<3.5 mmol/L/130 mg/dL). A total of 41 studies with 4667 paediatric patients at mean age 12.08 ± 2.4 years were included. Seventeen reported the efficacy and safety of LLT therapy compared to control, while the remaining assessed LLT through pre- and post-treatment. At median follow-up of 18.8 months, the group on LLT had significantly higher mean reductions of TC, LDL-C, TG, and increased HDL-C compared to control [−1.75 mmol/L (−67.7 mg/dL), −1.84 mmol/L (−71.2 mg/dL), −0.11 mmol/L (−9.74 mg/dL), 0.08 mmol/L (3.1 mg/dL), respectively, P < 0.001 for all]. In the subgroup analysis according to different types of LLT, we observed a significantly higher mean reduction of LDL-C by statin combined with ezetimibe treatment, followed by statins in monotherapy, PCSK9 inhibitors, and monotherapy with ezetimibe [−2.48 mmol/L (−95.9 mg/dL), −2.16 mmol/L (−83.5 mg/dL), −2.03 mmol/L (−78.5 mg/dL), and −1.50 mmol/L (−58 mg/dL), respectively, test for overall effect: P < 0.001]. The pooled LDL-C was reduced by 33.44% [−2.14 mmol/L (−82.8 mg/dL), P < 0.001] and failed to reach the goal treatment (<3.5 mmol/L) by 12.6% (95% CI, 12.4–12.9%). A total of 38.7% of children achieved the LDL-C goal, 23.9% fell short by up to 10%, 10.7% experienced moderate failure (were over the LDL-C target between >10% and 20%), and 26.7% failed by more than 20% to reach the LDL-C target. When comparing different regions, only Sweden and Greece achieved the LDL-C goal < 3.5 mmol/L in the follow-up. Netherlands, Norway, Poland, USA, UK, France, Spain, Belgium, and Austria required 2.2%, 3.4%, 3.5%, 8.9%, 10.2%, 11.2%, 11.2%, 15%, and 19.4% additional reduction in LDL-C respectively to achieve the LDL-C goal of < 3.5 mmol/L. All other countries required over 20% additional reduction in LDL-C to achieve the LDL-C goal. For other investigated countries, over 20% mean LDL-C reduction was required. All parameters related to endocrine function and demographic indices were unaffected by LLT therapy (P > 0.05). The AEs were not reported significantly higher when compared to the control, and the prevalence of therapy discontinuation was only 0.8%. Conclusion Despite the efficacy of LLT in children with HeFH and the low occurrence of discontinuation-related adverse events, achieving LDL-C treatment goals was relatively rare, with large differences between the investigated countries. These results underscore the importance of considering early combination therapy of statins and ezetimibe, and PCSK9 inhibitors (if available) to attain LDL-C goals effectively.
Source: European Heart Journal Open
Authors: Ibadete Bytyçi, Sefer Bytyqi, Joanna Lewek, Stanislaw Surma, Gani Bajraktari, Michael Henein, Amirhossein Sahebkar, Mutaz Al-Khnifsawi, Ioanna Gouni-Berthold, Ivan Pećin, Peter P Toth, Francesco Paneni, Niki Katsiki, Carlos Escobar, Carl J Lavie, Dan Gaita, Raul D Santos, Arrigo F G Cicero, Agata Bielecka-Dabrowa, Ali Ahmed, Maciej Banach
Institutions: University Clinical Center of Kosovo, University of Prishtina, Umeå University, Medical University of Lodz, Polish Mother’s Memorial Hospital Research Institute, Medical University of Silesia, University of Siena, Imperial College London, Mashhad University of Medical Sciences, Saveetha University, University of Al-Qadisiyah, University of Cologne, University Hospital Cologne, University Hospital Centre Zagreb, University of Zagreb, Johns Hopkins University, Johns Hopkins Medicine, CGH Medical Center, University of Zurich, University Hospital Zurich, International Hellenic University, European University Cyprus, Hospital Universitario La Paz, The University of Queensland, Victor Babeș University of Medicine and Pharmacy Timișoara, Universidade de São Paulo, Hospital Israelita Albert Einstein, Hospital Universitário da Universidade de São Paulo, Instituto do Coração - HCFMUSP, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, University of Bologna, Georgetown University, George Washington University, Veterans Health Administration, Washington DC VA Medical Center, John Paul II Catholic University of Lublin
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,688
OpenAlex ID: W4406326178