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. 2022 Apr 4:13:832614.
doi: 10.3389/fphar.2022.832614. eCollection 2022.

Efficacy and Safety of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors as Adjuvant Treatments for Patients with Hypercholesterolemia Treated with Statin: A Systematic Review and Network Meta-analysis

Yi-Ting Huang  1 , Li-Ting Ho  1   2   3 , Hsin-Yin Hsu  1   4   5 , Yu-Kang Tu  1 , Kuo-Liong Chien  1   2
Affiliations

Efficacy and Safety of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors as Adjuvant Treatments for Patients with Hypercholesterolemia Treated with Statin: A Systematic Review and Network Meta-analysis

Yi-Ting Huang et al. Front Pharmacol. .

Abstract

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent LDL-C lowering agents. However, few head-to-head studies evaluated the efficacy on the lowering in other atherogenic apolipoproteins and safety of PCSK9 inhibitors at different dosages as an add-on statins therapy in hypercholesterolemia patients. Methods: This study is a systematic review and network meta-analysis of randomized control trials to compare the efficacy of lipid reduction and adverse events of PCSK9 inhibitors in statin-treated hypercholesterolemia patients. PubMed, EMBASE, and Cochrane Library databases were searched till April 20, 2021, for randomized controlled trials. Random-effect network meta-analyses were undertaken to compare the differences in the percent reduction in low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) [Lp(a)] levels and the risk of AEs among different PCSK9 inhibitors. Results: A total of 22 articles with 42,786 patients were included. The lipid reductions in LDL-C, ApoB, and Lp(a) with add-on PCSK9 inhibitors vs. placebo in statin-treated patients across all trials were 50-63%, 43-52%, and 23-31%, respectively. Evolocumab 140 mg Q2W was ranked the best among all treatment strategies for lowering LDL-C, ApoB, and Lp(a) levels, and the treatment difference was 68.05% (95% confidence interval (CI), 62.43% to 73.67) in LDL-C reduction, 54.95% (95% CI, 49.55% to 60.35%) in ApoB reduction, and 34.25% (95% CI, 27.59% to 40.91%) in Lp(a) reduction compared with the placebo. No significant risk difference of adverse events between PCSK9 inhibitors and placebo was found. Conclusion: PCSK9 inhibitors showed a significant effect on the reduction in LDL-C, ApoB, and Lp(a) levels in statin-treated patients. Evolocumab 140 mg Q2W showed significantly larger degrees of LDL-C, ApoB, and Lp(a) reduction.

Keywords: PCSK9 inhibitors; add-on therapy; atherogenic apolipoproteins; hypercholesterolemia; low-density lipoprotein cholesterol.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of study identification and eligibility.
FIGURE 2
FIGURE 2
Network geometry of low-density lipoprotein cholesterol. The sizes of treatment nodes reflect the number of patients randomly assigned to each treatment. The thicknesses of edges represent the number of studies underlying each comparison.
FIGURE 3
FIGURE 3
Differences in percentage changes in low-density lipoprotein cholesterol, ApoB, and lipoprotein (a) obtained by network meta-analysis. Comparisons should be read from left to right. A positive value favors the column treatment.
FIGURE 4
FIGURE 4
Odds ratios of adverse events, nasopharyngitis, injection-site reaction, and serious adverse events obtained by network meta-analysis. Comparisons should be read from left to right. An odds ratio smaller than 1 favors the column treatment.
See this image and copyright information in PMC

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