{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:27:59Z","timestamp":1789820879105,"version":"4.0.1"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>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 (&amp;lt;3.5\u2005mmol\/L\/130\u2005mg\/dL). A total of 41 studies with 4667 paediatric patients at mean age 12.08 \u00b1 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 [\u22121.75 mmol\/L (\u221267.7 mg\/dL), \u22121.84 mmol\/L (\u221271.2 mg\/dL), \u22120.11 mmol\/L (\u22129.74 mg\/dL), 0.08 mmol\/L (3.1 mg\/dL), respectively, P &amp;lt; 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 [\u22122.48 mmol\/L (\u221295.9 mg\/dL), \u22122.16 mmol\/L (\u221283.5 mg\/dL), \u22122.03 mmol\/L (\u221278.5 mg\/dL), and \u22121.50 mmol\/L (\u221258 mg\/dL), respectively, test for overall effect: P &amp;lt; 0.001]. The pooled LDL-C was reduced by 33.44% [\u22122.14\u2005mmol\/L (\u221282.8\u2005mg\/dL), P &amp;lt; 0.001] and failed to reach the goal treatment (&amp;lt;3.5\u2005mmol\/L) by 12.6% (95% CI, 12.4\u201312.9%). 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 &amp;gt;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 &amp;lt; 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 &amp;lt; 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 &amp;gt; 0.05). The AEs were not reported significantly higher when compared to the control, and the prevalence of therapy discontinuation was only 0.8%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjopen\/oeaf001","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T19:08:02Z","timestamp":1736795282000},"source":"Crossref","is-referenced-by-count":8,"title":["Management of children with heterozygous familial hypercholesterolaemia worldwide: a meta-analysis"],"prefix":"10.1093","volume":"5","author":[{"given":"Ibadete","family":"Byty\u00e7i","sequence":"first","affiliation":[{"name":"Clinic of Cardiology, University Clinical Centre of Kosovo , Mati I 37, 10000 Prishtina, Kosovo"},{"name":"Department of Public Health and Clinical Medicine, Ume\u00e5 University , 90187 Ume\u00e5 ,","place":["Sweden"]},{"name":"Medical Faculty, University of Prishtina , Rrethi i Spitalit, pn., 10000 Prishtina, Kosovo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sefer","family":"Bytyqi","sequence":"additional","affiliation":[{"name":"Riinvest College , Lidhja e Prizrenit no.56, Prishtina, Kosovo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Lewek","sequence":"additional","affiliation":[{"name":"Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL) , Rzgowska 281\/289, 93-338 Lodz ,","place":["Poland"]},{"name":"Department of Cardiology and Congenital Diseases of Adults, Polish Mother\u2019s Memorial Hospital Research Institute (PMMHRI) , Rzgowska 281\/289, 93-338 Lodz ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislaw","family":"Surma","sequence":"additional","affiliation":[{"name":"Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL) , Rzgowska 281\/289, 93-338 Lodz ,","place":["Poland"]},{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia , Medyk\u00f3w 18, 40-752 Katowice ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0410-968X","authenticated-orcid":false,"given":"Gani","family":"Bajraktari","sequence":"additional","affiliation":[{"name":"Clinic of Cardiology, University Clinical Centre of Kosovo , Mati I 37, 10000 Prishtina, Kosovo"},{"name":"Department of Public Health and Clinical Medicine, Ume\u00e5 University , 90187 Ume\u00e5 ,","place":["Sweden"]},{"name":"Medical Faculty, University of Prishtina , Rrethi i Spitalit, pn., 10000 Prishtina, Kosovo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Henein","sequence":"additional","affiliation":[{"name":"Imperial College London , SW7 2AZ, London ,","place":["UK"]},{"name":"University of Siena , 53100 Siena ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirhossein","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University , Chennai 602105 ,","place":["India"]},{"name":"Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences , Mashhad 9177948954 ,","place":["Iran"]},{"name":"Applied Biomedical Research Center, Mashhad University of Medical Sciences , Mashhad 9177948564 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutaz","family":"Al-Khnifsawi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Al-Qadisiyah , 58001 Diwaniyah ,","place":["Iraq"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Gouni-Berthold","sequence":"additional","affiliation":[{"name":"Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Faculty of Medicine and University Hospital , 50937 Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Pe\u0107in","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Metabolic Diseases, University Hospital Center Zagreb , Ki\u0161pati\u0107eva 12, 10000 Zagreb ,","place":["Croatia"]},{"name":"Zagreb School of Medicine, University of Zagreb , Ki\u0161pati\u0107eva 12, 10000 Zagreb ,","place":["Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P","family":"Toth","sequence":"additional","affiliation":[{"name":"CGH Medical Center , Sterling, IL 61081 ,","place":["USA"]},{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine , Baltimore, MD 21287 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Paneni","sequence":"additional","affiliation":[{"name":"Center for Translational and Experimental Cardiology, University Hospital Z\u00fcrich and University of Z\u00fcrich , 8952 Zurich ,","place":["Switzerland"]},{"name":"University Heart Center, University Hospital Zurich and University of Z\u00fcrich , 8091 Zurich ,","place":["Switzerland"]},{"name":"Department of Research and Education, University Hospital Zurich and University of Z\u00fcrich , 8091 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki","family":"Katsiki","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences and Dietetics, International Hellenic University , 57400 Thessaloniki ,","place":["Greece"]},{"name":"School of Medicine, European University Cyprus , 2404 Nicosia ,","place":["Cyprus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Escobar","sequence":"additional","affiliation":[{"name":"Cardiology Department, University Hospital La Paz, Paseo de la Castellana , 261, Fuencarral-El Pardo, 28046 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl J","family":"Lavie","sequence":"additional","affiliation":[{"name":"University of Queensland School of Medicine New Orleans , New Orleans, LA 70112 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Gaita","sequence":"additional","affiliation":[{"name":"Cardiology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy , Timisoara 300041 ,","place":["Romania"]},{"name":"Institute of Cardiovascular Diseases Timisoara , Timisoara 300041 ,","place":["Romania"]},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara , Timisoara 300041 ,","place":["Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul D","family":"Santos","sequence":"additional","affiliation":[{"name":"Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital , Av. Dr. Eneas C. Aguiar 44, Sao Paulo 05403-900 ,","place":["Brazil"]},{"name":"Academic Research Organization, Hospital Israelita Albert Einstein, Av. 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