Effect and safety of PCSK9 inhibitor in-hospital use on blood lipid level in the ACS patients: a systematic review and meta-analysis

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Main funding source(s): none Aims To evaluate the effect and safety of in-hospital use of the proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor on blood lipid levels in the acute coronary syndrome (ACS) patients. Methods We searched the PubMed, MEDLINE, Web of Science, Ovid and Cochrane Library electronic databases through July 2023 to identify randomized controlled trials (RCTs) and cohort studies using PCSK9 inhibitors during ACS hospitalization. Then we compared the PCSK9 inhibitor group with a placebo or a blank control group with the same background of lipid-lowering therapy. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias for the included studies. A software was used to analyze the changes in overall lipids from baseline and the adverse event rates. Results A total of 15 studies enrolling 3891 patients with ACS were eligible, including 10 RCTs (n = 1406) and 5 cohort studies (n = 2485). Treatment with PCSK9 inhibitors showed a greater reduction in low-density lipoprotein cholesterol (LDLC) (SMD=1.46, 95% CI: 1.16-1.76, P<0.01). The cumulative meta-analysis of follow-up time showed that the degree of LDLC reduction stabilized after 12 weeks (SMD=1.42 at 12 weeks, 95% CI: 1.06-1.79, P<0.01), and thus, PCSK9 inhibitors dramatically decreased LDLC levels in comparison to controls at both ≤12 weeks and 12–72 weeks. The LDLC levels with PCSK9 inhibitors that reached the recommended standards of AHA/ACC (≤1.8mmol/l) and ESC (≤1.4mmol/l) were 95% and 80% respectively, which were significantly higher than those of the control group (58% and 22%). PCSK9 inhibitors can also reduce the total cholesterol, triglycerides, apolipoprotein B, and lipoprotein (a), while increasing the high-density lipoprotein cholesterol, but they have no statistical significance in reducing apolipoprotein A1. Compared with placebo or blank control, the addition of PCSK9 inhibitor did not increase the occurrence of adverse events (RR =-0.01,95% CI:-0.19-0.18, P = 0.95) and serious adverse events (RR =-0.03, 95% CI:-0.48-0.43, P=0.91). Conclusion In-hospital use of PCSK9 inhibitors can significantly improve the blood lipid levels of ACS patients and increase the target LDLC attainment rate, with satisfactory safety and good tolerance.