Effect on C‐reactive protein levels of the addition of ezetimibe, bempedoic acid, or colchicine to statin treatment: A network meta‐analysis

• DOI: 10.1111/joim.13824
• Publication Date: 2024-07-11T17:49:33Z
• Authors: Sining Xie; Federica Galimberti; Elena Olmastroni; Alberico L. Catapano; Manuela Casula
• Keywords: Ezetimibe; Colchicine; Stroke; Residual risk

Dear Editor, Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide. Although several therapeutic options are available to reduce LDL-cholesterol (LDL-C), many patients continue experience major (CV) events. In ASCVD, inflammation plays a critical role, contributing significantly residual CV risk [1]. Several anti-inflammatory therapies have been evaluated risk, recently, U.S. Food Drug Administration approved use low-dose colchicine myocardial infarction (MI), stroke, coronary revascularization, or death in adult with established ASCVD multiple factors [2, 3]. Meta-analyses shown that (0.5–1.0 mg) can lead reduction C-reactive protein (CRP) levels by −0.36 mg/L (95%CI, −0.51 −0.20) artery [4, 5], −0.66 −0.98 −0.35) acute MI [6], which translates into 35% 44% events, respectively. Nevertheless, some studies suggested an effect lipid-lowering therapies. recent meta-analysis involving 171,668 subjects from 53 randomized control trials (RCTs), we demonstrated serum CRP concentration statins (−0.65 [95%CI, −0.87 −0.43]), bempedoic acid (−0.43 −0.67 −0.20]), ezetimibe (−0.28 −0.48 −0.08]), was independent LDL-C changes [7]. Given growing interest targeting further inclusion among preventive [8], it appears compare on plasma levels. Therefore, sought quantify additional adding acid, ezetimibe, added background statin treatment. Because no trial directly compares impact versus therapies, performed network according PRISMA guidelines. PubMed, Web Science, EMBASE, Cochrane Library, ClinicalTrial.gov were searched inception November 2023. Inclusion criteria as follows: (1) RCTs human, parallel design, phase II, III, IV; (2) English language; (3) using interventions top treatment (defined more than 80% treated at baseline); (4) reporting levels; (5) intervention duration 3 weeks. Pooled estimates assessed both fixed-effect random-effects models within Bayesian hierarchical setting, assuming equal heterogeneity across all comparisons. When significant detected (as determined t2 I2 statistics, p < 0.05), results model presented. We individual bias (RoB) tool [9]. Sensitivity analysis excluding high RoB evaluation. All analyses conducted gemtc package R (version 4.3.2). Additional information is provided Supporting Information section. A total 22,287 30 (Table S1; median follow-up: 4.5 months) included (22 for [18,386 subjects], [2961 5 [940 subjects]). Pairwise indicated reduced −0.75 (95% CI, −0.88 −0.61) (Fig. 1a) compared alone. meta-analysis, addition showed differences direct comparison add-on (−0.22 [95% −0.69 0.30]) (−0.44 −1.05 0.23]) 1b, Figure S1). Bempedoic therapy, not different reducing −0.72 0.29]) 1b). The comparing relative (Figure S2) sensitivity removing S2, Figures S3 S4) consistent. summary, our suggests be comparable short term raises question about will benefit most. general, data suggest patient goal therefore eligible combination achieve benefits terms achieved colchicine. Notably, although has consistently associated causal nature association [10]. Furthermore, may capture aspects chronic inflammatory processes. Further research warranted explore comparative medium- long-term these drugs overall systemic inflammation. Sining Xie Manuela Casula made contributions concept design. Federica Galimberti responsible acquisition, analysis, interpretation data. Elena Olmastroni did statistical analysis. prepared draft manuscript. authors contributed revision Alberico L. Catapano supervision study. thank members META-LIPID Group who unpublished data: Hiroshi Ogawa (for HIJ-PROPER trial), JoAnne Foody, Michael Louie trials). SX, FG, EO, MC report disclosures. No funding received this project. work ALC, MC, FG supported part grant Ricerca Corrente Italian Ministry Health IRCCS MultiMedica. ALC and/or honoraria advisory boards, consultancy, speaker bureaus Amarin, Amgen, Amryt, AstraZeneca, Daiichi Sankyo, Esperion, Ionis Pharmaceuticals, Medscape, Menarini, Merck, Novartis, Peer Voice, Pfizer, Recordati, Regeneron, Sandoz, Sanofi, Corpus, Ultragenyx, Viatris. confirm supporting findings study derived published articles (available main text section) authors. For information, see Table S1 List S2 Risk Bias evaluation each Network diagram treatments comparisons outcome "CRP levels" Analysis percentage Chart showing contribution low, moderate S4 Please note: publisher content functionality any supplied Any queries (other missing content) should directed corresponding author article.