Efficacy and safety of proprotein convertase subtilisin kexin type (PCSK9) inhibitors in patients with acute coronary syndrome: A systematic review and meta-analysis

Abstract

Background: The effect of proprotein convertase subtilisin kexin type (PCSK9) inhibitors on blood lipids and major adverse cardiovascular events (MACEs) is still controversial for acute coronary syndrome (ACS) patients. This study aimed to evaluate the efficacy and safety of PCSK9 inhibitors for ACS patients. Methods: We searched the following databases until March 2023: PubMed, Embase, Cochrane, Web of Science, CNKI, Chongqing VIP Database and Wan Fang Database. Finally, all randomized controlled trials, retrospective studies and prospective studies were included in the analysis. Results: A total of 20 studies involving 48,621 patients were included in this meta-analysis. The results demonstrated that PCSK9 inhibitors group was more beneficial for ACS patients compared to control group (receiving statins alone or placebo). The meta-analysis showed: there was no significant difference in high density lipoprotein cholesterol between PCSK9 inhibitors group and control group (standard mean difference = 0.17, 95% confidence interval [CI]: −0.02 to 0.36, P = .08), while the level of low density lipoprotein cholesterol in PCSK9 inhibitors group was lower than that in control group (standard mean difference = −2.32, 95% CI: −2.81 to −1.83, P < .00001). Compared with the control group, the PCSK9 inhibitors group also decreased the levels of total cholesterol and triglycerides (mean difference = −1.24, 95% CI: −1.40 to −1.09, P < .00001, mean difference = −0.36, 95% CI: −0.56 to −0.16, P = .0004). Moreover, compared with the control group, PCSK9 inhibitors group could reduce the incidence of MACEs (relative risk [RR] = 0.87, 95% CI: 0.83–0.91; P < .00001). However, this study showed that the incidence of drug-induced adverse events in PCSK9 inhibitors group was higher than that in the control group (RR = 1.15, 95% CI: 1.05–1.25, P < .0001). Conclusion: Although this study demonstrates that PCSK9 inhibitors have higher drug-induced adverse events, they can not only reduce low-density lipoprotein cholesterol levels but also reduce the incidence of MACEs simultaneously. However, these findings needed to be further verified through large sample, multicenter, double-blind randomized controlled trials.