Effect of monoclonal antibodies to PCSK9 on high-sensitivity C-reactive protein levels: A meta-analysis of 16 randomized controlled treatment arms

Sahebkar, A. and Di Giosia, P. and Stamerra, C. A. and Grassi, D. and Pedone, C. and Ferretti, G. and Bacchetti, T. and Ferri, C. and Giorgini, P. (2016) Effect of monoclonal antibodies to PCSK9 on high-sensitivity C-reactive protein levels: A meta-analysis of 16 randomized controlled treatment arms. British Journal of Clinical Pharmacology, 81 (6). pp. 1175-1190.

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Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging class of low-density lipoprotein cholesterol (LDL-C)-lowering agents. In spite of their known effects on lipids, the impact of these drugs on systemic inflammation is less known. We aimed to investigate the effect of PCSK9 inhibitors on high-sensitivity C-reactive protein (hs-CRP) levels through a meta-analysis of randomized controlled trials (RCTs). Methods A systematic literature search of Medline, SCOPUS and Google Scholar was conducted up to December 2015 to identify RCTs assessing changes in hs-CRP concentrations during treatment with PCSK9 inhibitors. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95 confidence interval (CI) as summary statistics. Results Sixteen treatment arms, with a total of 2546 participants, were included. Random-effects meta-analysis did not show any significant effect of PCSK9 inhibitors on hs-CRP levels (WMD: 0.002 mg l-1, CI: -0.017, 0.021; P = 0.807; I2 = 37.26). This effect size was robust, not sensitive to any single study, and not affected by the type of PCSK9 inhibitor (evolocumab: WMD: 0.002 mg l-1, CI: -0.02, 0.02; P = 0.855; alirocumab WMD: 0.15 mg l-1, CI: -0.11, 0.40; P = 0.259; I2 = 0), or dosing frequency (biweekly: WMD: 0.13 mg l-1, CI: -0.20, 0.46; P = 0.433; I2 = 55.19; monthly: WMD: 0.003 mg l-1, CI: -0.01, 0.01; P = 0.59; I2 = 0). Random-effects meta-regression did not suggest any association of changes in hs-CRP levels with changes in plasma LDL-C concentrations (P = 0.697) or cumulative dosage of the drug (P = 0.980). Conclusions This meta-analysis of RCTs did not suggest an effect of PCSK9 inhibitors on hs-CRP concentrations. © 2016 The British Pharmacological Society.

Item Type: Article
Additional Information: Cited By :51 Export Date: 16 February 2020 CODEN: BCPHB Correspondence Address: Di Giosia, P.; Department of Life, Health and Environmental Sciences, San Salvatore Hospital, University of l'Aquila, Delta 6 Building, V. le San Salvatore, Italy; email: paolo.dig@hotmail.it
Uncontrolled Keywords: atherosclerosis hs-CRP inflammation PCSK9 inhibitors pleiotropic effect alirocumab C reactive protein evolocumab high sensitivity C reactive protein low density lipoprotein cholesterol proprotein convertase subtilisin kexin type 9 protein protein inhibitor unclassified drug enzyme inhibitor monoclonal antibody PCSK9 protein, human proprotein convertase 9 Article cholesterol blood level familial hypercholesterolemia human priority journal protein blood level quantitative analysis randomized controlled trial (topic) antagonists and inhibitors blood immunology meta analysis metabolism Antibodies, Monoclonal C-Reactive Protein Cholesterol, LDL Enzyme Inhibitors Humans Randomized Controlled Trials as Topic
Subjects: QU Biochemistry
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib4 lib4
Date Deposited: 29 Feb 2020 06:43
Last Modified: 29 Feb 2020 06:43
URI: http://eprints.mums.ac.ir/id/eprint/13181

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