期刊
ATHEROSCLEROSIS
卷 325, 期 -, 页码 46-56出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2021.03.042
关键词
Familial hypercholesterolemia; LDL-Cholesterol; PCSK9 lowering medication; Genotype; Meta-analysis
资金
- National Institute for Health Research Applied Research Collaboration Northwest London
The study revealed that among patients diagnosed clinically as HeFH, the LDL-C reduction effect of PCSK9-targeting medications remains consistent regardless of different drug classes and genetic variants.
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.
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