Yuhua Jiang ^1* Yingying Wang ^2* ma sijia ^1* Linlin Qian ^1* Yeteng Jing ^1* Xi Chen ^1* Jinsheng Yang ^1*

• ¹ Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Science, Dongcheng, China
• ² Acupuncture and Moxibustion Hospital, China Academy of Chinese Medical Sciences, Beijing, Beijing Municipality, China

The objective is to assess the relative efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab, evolocumab, and inclisiran, in conjunction with potent statins like atorvastatin and rosuvastatin, in patients presenting with hyperlipidemia or heightened cardiovascular risk attributable to elevated low-density lipoprotein cholesterol (LDL-C).Methods: A systematic search was conducted utilizing databases including PubMed, Embase, and the Cochrane Library to explore lipid-lowering therapies in hyperlipidemia from their inception up to November 07, 2023. A network meta-analysis was conducted via Stata 17 software, and two authors independently finished the search, screening, and data abstraction.Results: A total of sixty-eight clinical studies involving 21,288 patients with hyperlipidemia were incorporated into the network meta-analysis. PSCK-9 inhibitors and potent statins significantly reduced LDL-C level from baseline versus placebo regardless of background therapy. Regarding the efficacy of lipid reduction, four principal medications were evaluated alongside evolocumab and atorvastatin (MD -3.41, 95%CI -4.81 to -2.00) and evolocumab with rosuvastatin(MD -3.44, 95%CI -5.10 to -1.78) versus placebo; alirocumab combined with rosuvastatin (MD -2.91, 95%CI -3.95 to -1.88) and alirocumab with atorvastatin (MD -2.90, 95%CI -3.97 to -1.84) versus placebo; Meanwhile, compared with placebo, evolocumab(MD -1.89, 95%CI -2.27 to -1.50), alirocumab(MD -1.83, 95%CI -2.09 to -1.57), rosuvastatin (MD -1.93, 95%CI -2.30 to -1.56) , Inclisiran (MD -1.68, 95%CI -2.10 to -1.27) and atorvastatin (MD -1.68, 95%CI -2.04 to -1.31) could also play a role in the treatment of LDL-C reduction. Moreover, the incidence of adverse events (AEs) was similar to that observed in the control group, which included both placebo and potent statin groups, with no significant differences identified in our study (P>0.05).The combination of PCSK9 inhibitors with robust statins like rosuvastatin and atorvastatin markedly decreases LDL-C levels in patients with hyperlipidemia when compared to placebo or monotherapy. Notably, the pairing of evolocumab and atorvastatin exhibited exceptional efficacy in this investigation. In the interim, the combination of PCSK9 inhibitors and potent statins demonstrates a notable safety profile when contrasted with the control group.