Abstract
Objectives The aim of this study was to provide the first study to systematically analyze the efficacy and safety of PCSK9-mAbs in the treatment of familial hypercholesterolemia (FH). Methods A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: “AMG 145”, “evolocumab”, “SAR236553/REGN727”, “alirocumab”, “RG7652”, “LY3015014”, “RN316/bococizumab”, “PCSK9”, and “familial hypercholesterolemia” up to November 2020. Study quality was assessed with the Cochrane Collaboration's tool, and publication bias was evaluated by a contour-enhanced funnel plot and the Harbord modification of the Egger test. After obtaining the data, a meta-analysis was performed using R software, version 4.0.3. Results A meta-analysis was performed on 7 clinical trials (926 total patients). The results showed that PCSK9-mAbs reduced the LDL-C level by the greatest margin, WMD −49.14%, 95% CI: −55.81 to −42.47%, on FH versus control groups. PCSK9-mAbs also significantly reduced lipoprotein (a) (Lp (a)), total cholesterol (TC), triglycerides (TG), apolipoprotein-B (Apo-B), and non-high-density lipoprotein cholesterol (non-HDL-C) levels and increased HDL-C and apolipoprotein-A1 (Apo-A1) levels of beneficial lipoproteins. Moreover, no significant difference was found between PCSK9-mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. Conclusion PCSK9-mAbs significantly decreased LDL-C and other lipid levels with satisfactory safety and tolerability in FH treatment.
Highlights
Familial hypercholesterolemia (FH) is a common genetic disorder that causes high low-density lipoprotein cholesterol (LDL-C) level from birth, which causes atherosclerotic plaque deposition in the arteries and a markedly increased risk of coronary heart disease (CHD) at a young age [1]
We obtained individual participant data from studies identified through systematic searches of the published literature performed using the Cochrane Library, PubMed/MEDLINE, and Embase databases up to November 2020
As a lipid outcome of evolocumab, a significant reduction in LDL-C level was achieved (WMD: −49.45%, 95% confidence interval (CI): −57.04 to -41.85%, I2: 99%, p < 0:01, Figure 4(a))
Summary
Familial hypercholesterolemia (FH) is a common genetic disorder that causes high low-density lipoprotein cholesterol (LDL-C) level from birth, which causes atherosclerotic plaque deposition in the arteries and a markedly increased risk of coronary heart disease (CHD) at a young age [1]. In FH, the most common defect is loss-of-function mutations in LDL receptor alleles. FH includes homozygous and heterozygous types that have different symptoms, risks, and treatments. The incidence of FH is approximately 1 in 200–500 individuals and confers a significant risk for premature cardiovascular disease (CVD) [3]. Study has reported that the risk of premature CHD is elevated approximately 20-fold in young untreated heterozygous FH men and that homozygous FH patients typically develop CHD by the second decade of life [4]
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