Abstract:

Objective To systematically evaluate the efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK9) inhibitors on atherosclerotic cardiovascular disease (ASCVD). Methods PubMed, Embase, Cochrane Library and Clinical Trails.gov were subject to the computer retrieval from the data of database construction to May 2022. The randomized controlled trials (RCTs) of PCSK9 inhibitors for ASCVD patients were screened and incorporated, and the meta analysis on conforming RCTs was performed with Review Manager 5.4 software. Results A total of 10 RCTs comprising 54 472 patients were enrolled. Efficacy analysis results showed that PCSK9 inhibitors could reduce the level of low-density lipoprotein cholesterol (LDL-C) by 49.26%(95%CI: -54.00 to -44.52, P<0.01) and significantly reduced the other five lipid levels compared with the control group. Percent atheroma volume (PAV) reduced by 1.1% (95%CI: -1.48 to 0.73, P<0.01) and the minimum fibrous cap thickness (FCT) increased by 31.32%(95%CI: 15.82 to -46.82, P<0.01) in the PCSK9 inhibitors group. PCSK9 inhibitors did not reduce the risk of cardiovascular death (RR=0.97, 95%CI: 0.86 to 1.10, P>0.05), and reduced the risk of myocardial infarction (RR=0.73, 95%CI 0.65 to 0.81, P<0.01) and stroke (RR=0.78, 95%CI 0.68 to 0.90, P<0.01). The incidence of serious adverse events (SAEs) between the PCSK9 inhibitors group and control group was similar (RR=0.97, 95%CI 0.95 to 1.00, P>0.05). The incidence of injection site reaction in the PCSK9 inhibitor group was higher (RR=1.57, 95%CI: 1.40 to 1.76, P<0.01). Differences in myalgia, neurocognitive reaction and incidence new-onset diabetes weren't statistically significant when compared to such indexes in the control group (P>0.05). Conclusion PCSK9 inhibitors is capable of significantly reducing the level of LDL-C, incidence of myocardial infarction and stroke without serious adverse reactions.

Key words: cardiovascular diseases, atherosclerosis, PCSK9 inhibitors, meta-analysis