Amirhossein Sahebkar1,2, Paolo Di Giosia3, Cosimo Andrea Stamerra3, Davide Grassi3, Claudio Pedone4, Gianna Ferretti5, Tiziana Bacchetti6, Claudio Ferri3, Paolo Giorgini3. 1. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. 3. Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy. 4. Area di Geriatria, Università Campus Biomedico di Roma, Rome, Italy. 5. Dipartimento di Scienze cliniche Specialistiche ed Odontostomatologiche (DISCO), Università Politecnica delle Marche, Ancona, Italy. 6. Dipartimento di Scienze della Vita e dell'Ambiente (DISVA), Università Politecnica delle Marche, Ancona, Italy.
Abstract
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; I(2) = 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; I(2) = 0%), or dosing frequency (biweekly: WMD: 0.13 mg l(-1) , CI: -0.20, 0.46; P = 0.433; I(2) = 55.19%; monthly: WMD: 0.003 mg l(-1) , CI: -0.01, 0.01; P = 0.59; I(2) = 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.
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; I(2) = 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; I(2) = 0%), or dosing frequency (biweekly: WMD: 0.13 mg l(-1) , CI: -0.20, 0.46; P = 0.433; I(2) = 55.19%; monthly: WMD: 0.003 mg l(-1) , CI: -0.01, 0.01; P = 0.59; I(2) = 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.
Authors: Marc S Sabatine; Robert P Giugliano; Stephen D Wiviott; Frederick J Raal; Dirk J Blom; Jennifer Robinson; Christie M Ballantyne; Ransi Somaratne; Jason Legg; Scott M Wasserman; Robert Scott; Michael J Koren; Evan A Stein Journal: N Engl J Med Date: 2015-03-15 Impact factor: 91.245
Authors: Eliano Pio Navarese; Michalina Kolodziejczak; Volker Schulze; Paul A Gurbel; Udaya Tantry; Yingfeng Lin; Maximilian Brockmeyer; David E Kandzari; Julia M Kubica; Ralph B D'Agostino; Jacek Kubica; Massimo Volpe; Stefan Agewall; Dean J Kereiakes; Malte Kelm Journal: Ann Intern Med Date: 2015-07-07 Impact factor: 25.391
Authors: José Tuñón; Lina Badimón; Marie-Luce Bochaton-Piallat; Bertrand Cariou; Mat J Daemen; Jesus Egido; Paul C Evans; Imo E Hoefer; Daniel F J Ketelhuth; Esther Lutgens; Christian M Matter; Claudia Monaco; Sabine Steffens; Erik Stroes; Cécile Vindis; Christian Weber; Magnus Bäck Journal: Cardiovasc Res Date: 2019-01-01 Impact factor: 10.787
Authors: Konstantinos C Koskinas; Stephan Windecker; Aliki Buhayer; Baris Gencer; Giovanni Pedrazzini; Christian Mueller; Stephan Cook; Olivier Muller; Christian M Matter; Lorenz Räber; Dik Heg; François Mach Journal: Clin Cardiol Date: 2018-11-26 Impact factor: 2.882
Authors: Haris Riaz; Safi U Khan; Noman Lateef; Swapna Talluri; Muhammad Shahzeb Khan; Milind Y Desai Journal: Eur Heart J Qual Care Clin Outcomes Date: 2020-04-01