Reduction of C-reactive protein, low-density lipoprotein cholesterol, and its relationship with cardiovascular events of different lipid-lowering therapies: A systematic review and meta-analysis of randomized controlled trials

Background: To evaluate the reductions of C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDL-C) in different lipid-lowering drugs, and to assess the relationships between the reductions of CRP, LDL-C, and cardiovascular (CV) events. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to September 1, 2021. Randomized controlled trials (RCTs) comparing statins, proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs), or ezetimibe against placebo with a treatment duration of at least 4 weeks and data on the effects of cholesterol-lowering interventions on LDL-C and CRP were included in this meta-analysis. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated. Results: Compared with placebo treatment, statins and ezetimibe treatments resulted in a significant decrease in LDL-C level (statins: WMD -47.94 mg/dL, 95% CI -51.21 to -44.67 mg/dL; ezetimibe: WMD -22.84 mg/dL, 95% CI -26.76 to -18.92 mg/dL) and CRP level (statins: WMD -0.67 mg/L, 95% CI -0.90 to -0.45 mg/dL; ezetimibe: -0.64 mg/L, 95% CI -1.07 to -0.21 mg/dL). Compared with placebo treatment, treatment with PCSK9-mAbs resulted in significant decrease in LDL-C level (WMD -54.24 mg/dL, 95% CI -59.77 to -48.70 mg/dL), while the concentration of CRP did not decrease significantly. Meta-regression analysis showed no significant association between change in CRP level and change in LDL-C level. Subgroup comparisons suggested that treatment with PCSK9-mAbs showed a greater reduction in LDL-C level when compared with the statins group and ezetimibe group, while the risks of CV death, myocardial infarction (MI), and stroke showed no significant differences. Conclusion: Based on the current study, our results suggested that statins, ezetimibe, and PCSK9-mAbs are effective in reducing LDL-C levels. Treatment with statins and ezetimibe also demonstrated a significant effect on CRP. The traditional lipid-lowering strategy including statin and ezetimibe showed similar benefit on CV outcomes compared with the PCSK9-mAbs treatment.