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A meta-analysis of medications directed against PCSK9 in familial hypercholesterolemia
dc.creator | Brandts, Julia | es |
dc.creator | Dharmayat, Kanika I. | es |
dc.creator | Vallejo Vaz, Antonio Javier | es |
dc.creator | Azar Sharabiani, Mansour Taghavi | es |
dc.creator | Jones, Rebecca | es |
dc.creator | Kastelein, John J.P. | es |
dc.creator | Raal, Frederick J. | es |
dc.creator | Ray, Kausik K. | es |
dc.date.accessioned | 2022-10-11T15:38:19Z | |
dc.date.available | 2022-10-11T15:38:19Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Brandts, J., Dharmayat, K.I., Vallego Vaz, A.J., Azar Sharabiani, M.T., Jones, R., Kastelein, J.J.P.,...,Ray, K.K. (2021). A meta-analysis of medications directed against PCSK9 in familial hypercholesterolemia. Atherosclerosis, 325, 46-56. https://doi.org/10.1016/j.atherosclerosis.2021.03.042. | |
dc.identifier.issn | 0021-9150 | es |
dc.identifier.issn | 1879-1484 | es |
dc.identifier.uri | https://hdl.handle.net/11441/137826 | |
dc.description.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. | es |
dc.format | application/pdf | es |
dc.format.extent | 11 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier Ireland | es |
dc.relation.ispartof | Atherosclerosis, 325, 46-56. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Familial hypercholesterolemia | es |
dc.subject | LDL-Cholesterol | es |
dc.subject | PCSK9 lowering medication | es |
dc.subject | Genotype | es |
dc.subject | Meta-analysis | es |
dc.title | A meta-analysis of medications directed against PCSK9 in familial hypercholesterolemia | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.publisherversion | http://doi.org/10.1016/j.atherosclerosis.2021.03.042 | es |
dc.identifier.doi | 10.1016/j.atherosclerosis.2021.03.042 | es |
dc.journaltitle | Atherosclerosis | es |
dc.publication.volumen | 325 | es |
dc.publication.initialPage | 46 | es |
dc.publication.endPage | 56 | es |