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Meta-Analysis
. 2015 Jun 15;4(6):e001937.
doi: 10.1161/JAHA.115.001937.

Efficiency and safety of proprotein convertase subtilisin/kexin 9 monoclonal antibody on hypercholesterolemia: a meta-analysis of 20 randomized controlled trials

Chuanwei Li  1 , Ling Lin  2 , Wen Zhang  3 , Liang Zhou  4 , Hongyong Wang  1 , Xiaoli Luo  1 , Hao Luo  1 , Yue Cai  1 , Chunyu Zeng  1
Affiliations
Meta-Analysis

Efficiency and safety of proprotein convertase subtilisin/kexin 9 monoclonal antibody on hypercholesterolemia: a meta-analysis of 20 randomized controlled trials

Chuanwei Li et al. J Am Heart Assoc. .

Abstract

Background: Proprotein convertase subtilisin/kexin9 (PCSK9) monoclonal antibody significantly reduces low-density lipoprotein cholesterol level in patients with hypercholesterolemia. The goal of this study was to review recently reported randomized controlled trials to investigate the therapeutic effects and safety of PCSK9 inhibitors.

Methods and results: The clinical randomized controlled trials published from inception to March 19, 2015 were identified from The Cochrane Library databases, PUBMED, and EBASE. Randomized controlled trials of at least 8 weeks duration using PCSK9 inhibitors in treating patients with hypercholesterolemia were included. Mean difference (MD) with a 95% CI was used to calculate the continuous data, the standardized mean difference with a 95% CI was used when the unit was not unified, and risk ratio with a 95% CI was used for dichotomous data. After screening, 20 trials fulfilled the inclusion criteria. PCSK9 inhibitors significantly decreased the levels of low-density lipoprotein cholesterol (MD=-65.29 mg/dL, 95% CI: -72.08 to -58.49), total cholesterol (MD=-60.04 mg/dL, 95% CI: -69.95 to -50.13), triglycerides (MD=-12.21 mg/dL, 95% CI: -16.21 to -8.22) and apolipoprotein-B (MD=-41.01 mg/dL, 95% CI: -46.07 to -35.94), lipoprotein(a) (standardized mean difference=-0.94, 95% CI: -1.12 to -0.77) and increased the levels of high-density lipoprotein cholesterol (MD=3.40 mg/dL, 95% CI: 3.12 to 3.68) and apolipoprotein-A1 (MD=6.75 mg/dL, 95% CI: 4.64 to 8.86). There was no significant difference in the incidence of treatment-emergent adverse events (risk ratio=1.01, 95% CI: 0.98 to 1.04), serious treatment-emergent adverse events (risk ratio=1.01, 95% CI: 0.88 to 1.17), and the discontinuation of treatment between the 2 groups (risk ratio=1.07, 95% CI: 0.86 to 1.34).

Conclusions: The meta-analysis indicated that PCSK9 inhibitors had a strong effect in lowering low-density lipoprotein cholesterol and other lipid levels with satisfactory safety and tolerability in patients with hypercholesterolemia.

Keywords: lipids; lipoproteins; meta‐analysis; proprotein convertase subtilisin/kexin9 inhibitor.

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Figures

Figure 1
Figure 1
Preferred reporting items for systematic review and meta-analysis (PRISMA) flowchart of the process of study selection.
Figure 2
Figure 2
Risk-of-bias graph: review authors’ judgments about each risk-of-bias item presented as percentages across all included studies.
Figure 3
Figure 3
Forest plots depicting the effect of PCSK9 monoclonal antibodies on LDL-C. LDL-C indicates low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin9.
Figure 4
Figure 4
Forest plots depicting the effect of PCSK9 monoclonal antibodies on TC. PCSK9 indicates proprotein convertase subtilisin/kexin9; TC, total cholesterol.
Figure 5
Figure 5
Forest plots depicting the effect of PCSK9 monoclonal antibodies on HDL-C. HDL-C indicates high-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin9.
Figure 6
Figure 6
Forest plots depicting the effect of PCSK9 monoclonal antibodies on TG. PCSK9 indicates proprotein convertase subtilisin/kexin9; TG, triglycerides.
Figure 7
Figure 7
Forest plots depicting the effect of PCSK9 monoclonal antibodies on APO-B. APO-B indicates apolipoprotein-B; PCSK9, proprotein convertase subtilisin/kexin9.
Figure 8
Figure 8
Forest plots depicting the effect of PCSK9 monoclonal antibodies on APO-A1. APO-A1 indicates apolipoprotein-A1; PCSK9, proprotein convertase subtilisin/kexin9.
Figure 9
Figure 9
Forest plots depicting the effect of proprotein convertase subtilisin/kexin9 monoclonal antibodies on lipoprotein(a).
Figure 10
Figure 10
Forest plots depicting the effect on low-density lipoprotein cholesterol for subgroup analysis after grouping by methods of treatment.
Figure 11
Figure 11
Forest plots depicting the effect on low-density lipoprotein cholesterol for subgroup analysis after grouping by enrolled patients.
Figure 12
Figure 12
Forest plots depicting the effect on low-density lipoprotein cholesterol for subgroup analysis after grouping by treatment duration.
Figure 13
Figure 13
Forest plot depicting the treatment-emergent adverse events of proprotein convertase subtilisin/kexin9 monoclonal antibodies.
Figure 14
Figure 14
Forest plots depicting the serious treatment-emergent adverse events of proprotein convertase subtilisin/kexin9 monoclonal antibodies.
Figure 15
Figure 15
Forest plots depicting the treatment-associated withdrawal.
See this image and copyright information in PMC

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