PMID- 36417822 OWN - NLM STAT- MEDLINE DCOM- 20221206 LR - 20221206 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 113 IP - Pt B DP - 2022 Dec TI - The effect of combination therapy with statins and ezetimibe on proinflammatory cytokines: A systematic review and meta-analysis of randomized controlled trials. PG - 109477 LID - S1567-5769(22)00962-6 [pii] LID - 10.1016/j.intimp.2022.109477 [doi] AB - It remains unknown whether statin therapy in combination with ezetimibe is a beneficial and equivalent alternative to statin monotherapy in reducing proinflammatory cytokines. In the present systematic review and meta-analysis, we aimed to assess the effect of combination therapy with statins and ezetimibe on some proinflammatory cytokines. Databases, including MEDLINE, SciVerse, Scopus, and Clarivate Analytics Web of Science databases, were searched up to February 2022, for terms related to combination therapy with statins and ezetimibe and proinflammatory cytokines. The quality of the included studies was evaluated with Cochrane risk of bias tool 1, and weighted mean difference [WMD] and SD of changes were used for meta-analysis. The results were expressed as differences in means and 95 % CIs with an inverse variance and a random-effects model. Finally, 12 studies [13 arms] were included in the qualitative and quantitative synthesis. The average patient's age ranged from 49.3 to 71 years, and the duration of intervention lasted seven days to 12 months. Overall, our result did not show any significant reduction in interleukin-1beta (IL-1beta) (3 randomized controlled trial studies (RCTs), 292 participants, WMD: -0.4 pg/ml; 95 % CI: -1.3, 0.4, P = 0.3, I(2) = 93.1 %, P < 0.001), tumor necrosis factor-alpha (TNF-alpha) (4 RCTs, 199 participants, WMD: -0.3 pg/ml; 95 % CI: -0.8, 0.1, P = 0.1, I(2) = 13.8 %, P = 0.3) and monocyte chemoattractant protein-1 (MCP-1) (4 RCTs, 216 participants, WMD: -7.8 pg/ml; 95 % CI: -18.5, 2.8, P = 0.1, I(2) = 30.8 %, P = 0.2). However, there was a significant reduction in interleukin-6 (IL-6) (9 RCTs, 514 participants, WMD: -1.4 pg/ml; 95 % CI: -2.4, -0.3, P < 0.007, I(2) = 97.1 %, P < 0.001) and interferon-gamma (IFN-gamma) (2 RCTs, 78 participants, WMD: -0.2 pg/ml; 95 % CI: -0.4, -0.1, P < 0.001, I(2) = 0 %, P = 0.7). Following subgroup analysis, there was a significant reduction in IL-6 in the age group >/= 60 years and the Asian population. Statin therapy in combination with ezetimibe causes a significant decrease in IL-6 and IFN-gamma, and the reduction in IL-6 is significant in >/= 60 years and the Asian population. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Mostafa Arabi, Seyyed AU - Mostafa Arabi S AD - Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Sadat Bahrami, Leila AU - Sadat Bahrami L AD - Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - MalekAhmadi, Mahsa AU - MalekAhmadi M AD - Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran; Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. FAU - Chambari, Mahla AU - Chambari M AD - Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran. FAU - Milkarizi, Narges AU - Milkarizi N AD - Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran. FAU - Orekhov, Alexander N AU - Orekhov AN AD - Institute of General Pathology and Pathophysiology, 8, Baltiiskaya Street, Moscow 125315, Russia; Institute for Atherosclerosis Research, Osennyaya Street 4-1-207, Moscow 121609, Russia. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Medicine, The University of Western Australia, Perth, Australia; Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: sahebkara@mums.ac.ir. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20221120 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Cytokines) RN - EOR26LQQ24 (Ezetimibe) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 82115-62-6 (Interferon-gamma) RN - 0 (Interleukin-6) SB - IM MH - Humans MH - Middle Aged MH - Cytokines MH - Ezetimibe/therapeutic use MH - *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Interferon-gamma MH - Interleukin-6 MH - Randomized Controlled Trials as Topic MH - Aged OTO - NOTNLM OT - Ezetimibe OT - Proinflammatory cytokines OT - Statins COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/11/24 06:00 MHDA- 2022/12/03 06:00 CRDT- 2022/11/23 18:19 PHST- 2022/10/06 00:00 [received] PHST- 2022/11/14 00:00 [revised] PHST- 2022/11/15 00:00 [accepted] PHST- 2022/11/24 06:00 [pubmed] PHST- 2022/12/03 06:00 [medline] PHST- 2022/11/23 18:19 [entrez] AID - S1567-5769(22)00962-6 [pii] AID - 10.1016/j.intimp.2022.109477 [doi] PST - ppublish SO - Int Immunopharmacol. 2022 Dec;113(Pt B):109477. doi: 10.1016/j.intimp.2022.109477. Epub 2022 Nov 20.