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A meta-analysis of medications directed against PCSK9 in familial hypercholesterolemia
Title: | A meta-analysis of medications directed against PCSK9 in familial hypercholesterolemia |
Authors: | Brandts, J Dharmayat, KI Vallejo-Vaz, AJ Azar Sharabiani, MT Jones, R Kastelein, JJP Raal, FJ Ray, KK |
Item Type: | Journal Article |
Abstract: | BACKGROUND AND AIMS: Several medications targeting PCSK9 reduce LDL-cholesterol (LDL-C) in heterozygous familial hypercholesterolemia (HeFH). We aimed to assess in patients diagnosed clinically as HeFH, whether LDL-C reduction varied by different therapeutic approaches to PCSK9-targeting or by the underlying genetic variant. METHODS: We conducted a random-effects meta-analysis of randomised clinical trials assessing PCSK9-targeting therapies, namely alirocumab, evolocumab and inclisiran, in patients with clinically diagnosed HeFH and restricted analyses to those patients in whom genotypic data were available. A search of MEDLINE and Embase identified eligible trials published between inception and June 29, 2020. We included trials of sufficient duration to allow for a stable treatment effect: ~12 weeks for monoclonal antibodies (mAbs) (alirocumab, evolocumab) and ~1 year for small interfering RNA (siRNA) (inclisiran). Single-moderator meta-regression comparing mean percentage LDL-C reduction between mAbs and siRNA as well as PCSK9-targeting therapies between different genotypes was used to assess heterogeneity. RESULTS: Eight trials of HeFH met our inclusion criteria, including 1887 genotyped patients. Among monogenic HeFH cases (N = 1347) the LDL-C reduction from baseline was 46.12% (95%CI 48.4-43.9) for siRNA and 50.4% (59.3-41.4) for mAbs compared to control, without evidence of significant heterogeneity between treatment (QM = 0.32, df = 1, p = 0.57). Irrespective of therapeutic approach to PCSK9-targeting, reductions in LDL-C were generally consistent across genetic variants (LDL-Receptor variants, LDL-Receptor variants of unknown significance, Apolipoprotein B variants, two variants and no variant) (QM = 8.3, df = 4, p = 0.08). CONCLUSIONS: Among patients with HeFH, the LDL-C-lowering effect of PCSK9-targeting medications did not show statistical heterogeneity across different drug-classes and across genetic variants. |
Issue Date: | 1-May-2021 |
Date of Acceptance: | 31-Mar-2021 |
URI: | http://hdl.handle.net/10044/1/89241 |
DOI: | 10.1016/j.atherosclerosis.2021.03.042 |
ISSN: | 0021-9150 |
Publisher: | Elsevier |
Start Page: | 46 |
End Page: | 56 |
Journal / Book Title: | Atherosclerosis |
Volume: | 325 |
Copyright Statement: | © 2021 Elsevier B.V. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Keywords: | Familial hypercholesterolemia Genotype LDL-Cholesterol Meta-analysis PCSK9 lowering medication Familial hypercholesterolemia Genotype LDL-Cholesterol Meta-analysis PCSK9 lowering medication 1102 Cardiorespiratory Medicine and Haematology 1103 Clinical Sciences Cardiovascular System & Hematology |
Publication Status: | Published |
Conference Place: | Ireland |
Online Publication Date: | 2021-04-20 |
Appears in Collections: | Library Central Services Faculty of Medicine School of Public Health |
This item is licensed under a Creative Commons License