Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials.

Abstract

To evaluate the potential effects of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9-mAb) on high-sensitivity C reactive protein (hs-CRP) concentrations. A systematic review and meta-analysis of randomised controlled trials. PubMed, MEDLINE, the Cochrane Library databases, ClinicalTrials.gov and recent conferences were searched from inception to May 2018. All randomised controlled trials that reported changes of hs-CRP were included. Ten studies involving 4198 participants were identified. PCSK9-mAbs showed a slight efficacy in reducing hs-CRP (-0.04 mg/L, 95% CI: -0.17 to 0.01) which was not statistically different. The results did not altered when subgroup analyses were performed including PCSK9-mAb types (alirocumab: 0.12 mg/L, 95% CI: -0.18 to 0.43; evolocumab: 0.00 mg/L, 95% CI: -0.07 to 0.07; LY3015014: -0.48 mg/L, 95% CI: -1.28 to 0.32; RG7652: 0.35 mg/L, 95% CI: -0.26 to 0.96), treatment duration (≤12w: 0.00 mg/L, 95% CI: -0.07 to 0.07; >12w: -0.11 mg/L, 95% CI: -0.45 to -0.23), participant characteristics (familial hypercholesterolaemia: 0.00 mg/L, 95% CI: -0.07 to 0.07; non-familial hypercholesterolaemia: 0.07 mg/L, 95% CI: -0.12 to 0.26; mix: -0.48 mg/L, 95% CI: -1.28 to 0.32) and treatment methods (monotherapy: 0.00 mg/L, -0.08 to 0.07; combination therapy: -0.08 mg/L, -0.37 to 0.21). Meta-regression analyses suggested no significant linear correlation between baseline age (p=0.673), sex (p=0.645) and low-density lipoprotein cholesterol reduction (p=0.339). Our updated meta-analysis suggested that PCSK9-mAbs had no significant impact on circulating hs-CRP levels irrespective of PCSK9-mAb types, participant characteristics and treatment duration or methods.