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

Objective

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.

Design

A systematic review and meta-analysis of randomised controlled trials.

Data sources

PubMed, MEDLINE, the Cochrane Library databases, ClinicalTrials.gov and recent conferences were searched from inception to May 2018.

Eligibility criteria for selecting studies

All randomised controlled trials that reported changes of hs-CRP were included.

Results

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).

Conclusions

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.

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