PCSK9 targeting therapies for familial hypercholesterolaemia: a meta-analysis of efficacy on lipid biomarkers and safety in adults and children across 23 RCTs
Background Familial hypercholesterolaemia (FH) is a hereditary disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels, substantially increasing the risk of atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) targeting therapies...
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BMJ Publishing Group
2025-08-01
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| Series: | Open Heart |
| Online Access: | https://openheart.bmj.com/content/12/2/e003490.full |
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| author | Vinh Q T Ho Nghi Bao Tran Nhan Nguyen Giang Son Arrighini David Downes Mrunalini Dandamudi Victoria Zecchin Ferrara Tri Huynh Quang Ho Hemank Walia Alejandro Barbagelata Thorsten M Leucker Juliana Giorgi |
| author_facet | Vinh Q T Ho Nghi Bao Tran Nhan Nguyen Giang Son Arrighini David Downes Mrunalini Dandamudi Victoria Zecchin Ferrara Tri Huynh Quang Ho Hemank Walia Alejandro Barbagelata Thorsten M Leucker Juliana Giorgi |
| author_sort | Vinh Q T Ho |
| collection | DOAJ |
| description | Background Familial hypercholesterolaemia (FH) is a hereditary disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels, substantially increasing the risk of atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) targeting therapies, including monoclonal antibodies and small interfering RNA (siRNA) agents, have emerged as effective lipid lowering therapies.Objective To assess the efficacy and safety of PCSK9-targeting therapy on lipid biomarkers and adverse events in patients with FH, compared with placebo on the background of standard lipid-lowering therapy.Methods A systematic review and meta-analysis were conducted, incorporating data from 23 randomised controlled trials involving adult and paediatric FH patients treated with PCSK9 inhibitors (PCSK9i) or siRNA, including alirocumab, bococizumab, evolocumab, tafolecimab and inclisiran. Eligible studies reported changes in LDL-C, apolipoprotein B (ApoB), lipoprotein a (Lp(a)), triglycerides (TGL) and adverse effects. Pooled mean differences (MDs) and ORs with 95% CIs were calculated using random-effects models, and heterogeneity was assessed with I² statistic. This meta-analysis was registered on PROSPERO (CRD42025631510).Results A total of 4282 patients were included. PCSK9-targeting therapies significantly reduced LDL-C levels compared with control therapies (MD=−46.64%; 95% CI −50.77% to –42.52%; p<0.00001) and TGL (MD=−15.18%; 95% CI –19.34% to –11.03%; p<0.00001). Significant reductions were also observed for ApoB (MD=−34.94%; 95% CI –40.89% to –28.99%; p<0.00001) and Lp(a) (MD=−22.7%; 95% CI −25.95% to –19.44%; p<0.00001). LDL-C, TGL and ApoB reduction were more significant in heterozygous FH patients than in homozygous patients. The safety profile of these therapies was favourable, with adverse event rates comparable to those of the controls.Conclusions PCSK9i and Inclisiran demonstrate significant and sustained reductions in LDL-C, ApoB, Lp(a) and TGL in FH patients, especially in heterozygous FH patients. These agents are generally well-tolerated and represent effective treatment options for FH patients inadequately controlled by standard lipid-lowering therapies. |
| format | Article |
| id | doaj-art-b8ef190699854fa9b0d4f45bf870739e |
| institution | Kabale University |
| issn | 2053-3624 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
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| series | Open Heart |
| spelling | doaj-art-b8ef190699854fa9b0d4f45bf870739e2025-08-21T11:25:13ZengBMJ Publishing GroupOpen Heart2053-36242025-08-0112210.1136/openhrt-2025-003490PCSK9 targeting therapies for familial hypercholesterolaemia: a meta-analysis of efficacy on lipid biomarkers and safety in adults and children across 23 RCTsVinh Q T Ho0Nghi Bao Tran1Nhan Nguyen2Giang Son Arrighini3David Downes4Mrunalini Dandamudi5Victoria Zecchin Ferrara6Tri Huynh Quang Ho7Hemank Walia8Alejandro Barbagelata9Thorsten M Leucker10Juliana Giorgi111 Faculty of Medicine, University of Debrecen, Debrecen, Hungary1 Faculty of Medicine, University of Debrecen, Debrecen, Hungary1 Faculty of Medicine, University of Debrecen, Debrecen, Hungary2 Faculty of Medicine and Surgery, University of Bologna, Bologna, Italy3 Department of Rural Medicine, University of New England, Armidale, New South Wales, Australia4 St Barnabas Health System Bronx, New York, New York, USA5 Faculty of Medicine and Surgery, University of Padova, Padua, Italy6 Surgical Intensive Care Unit, Ho Chi Minh City Heart Institute, Ho Chi Minh City, Vietnam7 Advocate Illinois Masonic Medical Center, Chicago, Illinois, USA8 Universidad Catolica Argentina, Buenos AIres, Argentina10 Johns Hopkins University, Baltimore, Maryland, USA11 Hospital Sirio-Libanes, São Paulo, BrazilBackground Familial hypercholesterolaemia (FH) is a hereditary disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels, substantially increasing the risk of atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) targeting therapies, including monoclonal antibodies and small interfering RNA (siRNA) agents, have emerged as effective lipid lowering therapies.Objective To assess the efficacy and safety of PCSK9-targeting therapy on lipid biomarkers and adverse events in patients with FH, compared with placebo on the background of standard lipid-lowering therapy.Methods A systematic review and meta-analysis were conducted, incorporating data from 23 randomised controlled trials involving adult and paediatric FH patients treated with PCSK9 inhibitors (PCSK9i) or siRNA, including alirocumab, bococizumab, evolocumab, tafolecimab and inclisiran. Eligible studies reported changes in LDL-C, apolipoprotein B (ApoB), lipoprotein a (Lp(a)), triglycerides (TGL) and adverse effects. Pooled mean differences (MDs) and ORs with 95% CIs were calculated using random-effects models, and heterogeneity was assessed with I² statistic. This meta-analysis was registered on PROSPERO (CRD42025631510).Results A total of 4282 patients were included. PCSK9-targeting therapies significantly reduced LDL-C levels compared with control therapies (MD=−46.64%; 95% CI −50.77% to –42.52%; p<0.00001) and TGL (MD=−15.18%; 95% CI –19.34% to –11.03%; p<0.00001). Significant reductions were also observed for ApoB (MD=−34.94%; 95% CI –40.89% to –28.99%; p<0.00001) and Lp(a) (MD=−22.7%; 95% CI −25.95% to –19.44%; p<0.00001). LDL-C, TGL and ApoB reduction were more significant in heterozygous FH patients than in homozygous patients. The safety profile of these therapies was favourable, with adverse event rates comparable to those of the controls.Conclusions PCSK9i and Inclisiran demonstrate significant and sustained reductions in LDL-C, ApoB, Lp(a) and TGL in FH patients, especially in heterozygous FH patients. These agents are generally well-tolerated and represent effective treatment options for FH patients inadequately controlled by standard lipid-lowering therapies.https://openheart.bmj.com/content/12/2/e003490.full |
| spellingShingle | Vinh Q T Ho Nghi Bao Tran Nhan Nguyen Giang Son Arrighini David Downes Mrunalini Dandamudi Victoria Zecchin Ferrara Tri Huynh Quang Ho Hemank Walia Alejandro Barbagelata Thorsten M Leucker Juliana Giorgi PCSK9 targeting therapies for familial hypercholesterolaemia: a meta-analysis of efficacy on lipid biomarkers and safety in adults and children across 23 RCTs Open Heart |
| title | PCSK9 targeting therapies for familial hypercholesterolaemia: a meta-analysis of efficacy on lipid biomarkers and safety in adults and children across 23 RCTs |
| title_full | PCSK9 targeting therapies for familial hypercholesterolaemia: a meta-analysis of efficacy on lipid biomarkers and safety in adults and children across 23 RCTs |
| title_fullStr | PCSK9 targeting therapies for familial hypercholesterolaemia: a meta-analysis of efficacy on lipid biomarkers and safety in adults and children across 23 RCTs |
| title_full_unstemmed | PCSK9 targeting therapies for familial hypercholesterolaemia: a meta-analysis of efficacy on lipid biomarkers and safety in adults and children across 23 RCTs |
| title_short | PCSK9 targeting therapies for familial hypercholesterolaemia: a meta-analysis of efficacy on lipid biomarkers and safety in adults and children across 23 RCTs |
| title_sort | pcsk9 targeting therapies for familial hypercholesterolaemia a meta analysis of efficacy on lipid biomarkers and safety in adults and children across 23 rcts |
| url | https://openheart.bmj.com/content/12/2/e003490.full |
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