Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor LDL-R by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), SCARB1 scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson's disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development 1).

Conventional lipid-lowering agents, including statins, ezetimibe, fibrates, bile acid sequestrants, nicotinic acid, bempedoic acid and Omega-3 fatty acid, are essential to the management of dyslipidemia. However, these agents have been shown to increase the level of plasma proprotein convertase subtilisin/kexin 9 (PCSK9), a serine protease associated with increased - cardiovascular risk.

A review of Luo et al. aimed to investigate the impact of commonly available conventional lipid-lowering agents on circulating PCSK9 levels and lipid profiles.

This protocol was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. A systematic literature search will be conducted in the following databases: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, SCOPUS and ScienceDirect. Additional information will be retrieved from clinical trial registries or from reference list searches. Published and peer-reviewed randomised controlled trials with adults receiving statin, ezetimibe, fibrate, bile acid sequestrant, nicotinic acid, bempedoic acid or Omega-3 monotherapy or in combination for at least 2 weeks, with availability of plasma PCSK9 at the beginning and end of treatment or the net changes in values, will be included. Study selection, data extraction and assessment of the risk of bias will be independently conducted by two investigators. Continuous data will be presented as a standardised mean difference with 95% confidence interval (CI) and dichotomous data as risk ratios with 95% CI. Subgroup analysis and sensitivity analysis will be performed when sufficient studies are included. Publication bias will be assessed with a funnel plot and Egger's test. 2). 3)

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Luo J, Huang T, Xu R, Wang X, Yang Y, Li L, Zhang X, Zhang Y, Yang R, Wang J, Yang H, Ma Y, Yang B, Wang T, Jiao L. Impact of conventional lipid-lowering therapy on circulating levels of PCSK9: protocol for a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2022 Sep 8;12(9):e061884. doi: 10.1136/bmjopen-2022-061884. PMID: 36691198.
Luo J, Liao W, Wang X, Xu R, Li W, Li W, Liu K, Huang K, Ma Y, Wang T, Yang B, Jiao L. PCSK9 inhibitors for anti-inflammation in atherosclerosis: protocol for a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2022 Nov 24;12(11):e062046. doi: 10.1136/bmjopen-2022-062046. PMID: 36424111; PMCID: PMC9693878.
  • pcsk9.txt
  • Last modified: 2023/01/24 09:22
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