BackgroundThere is no consensus at present regarding the differences in the risk of GI bleeding across various NOAC regimens. Therefore, we performed a network meta-analysis to compare the risk of gastrointestinal bleeding after different NOAC regimens.MethodsPubMed, Cochrane, Web of Science, Clinicaltrial.gov and Clinicaltrialresults.org were searched for randomized controlled trials (RCTs) assessing gastrointestinal bleeding of all NOAC regimens from inception to January 2018. The primary endpoint was major gastrointestinal (MGI) bleeding. The meta-regression was performed to access the association between the MGI bleeding events and mortality. The network meta-analysis was carried out with the Bayesian random-effect model.ResultsA total of 25 RCTs, including 139,392 patients, were identified. Meta-regression analysis showed that MGI bleeding was correlated with fatal bleeding events (odds ratios [OR], 1.76; 95% confidence interval [CI], 1.13–2.77], P=0.015). The network meta-analysis results showed that compared to the conventional regimens, rivaroxaban was associated with increased risk of MGI bleeding (OR, 1.37; 95% credible interval [CrI], 1.00–1.85), but not the apixaban (OR, 0.77; 95% CrI, 0.53–1.07]), edoxaban (OR, 0.86; 95%CrI, 0.52–1.18) and dabigatran etexilate (OR, 1.22; 95% CrI, 0.82–1.69). Compared to rivaroxaban, apixaban (OR, 0.56; 95% CrI, 0.35–0.88) and edoxaban (OR, 0.62; 95% CrI, 0.35–0.96) showed a significantly lower risk of MGI bleeding. Apixaban had the highest probability of being the safest option with regard to the risk of MGI bleeding (89.1%), followed by edoxaban (77.4%), conventional therapy (51.4%), dabigatran etexilate (23.8%) and rivaroxaban (8.3%).ConclusionThe risk of GI bleeding significantly varies among different NOAC regimens, and evidence shows that apixaban and edoxaban had the most favorable MGI bleeding safety profile, while rivaroxaban and dabigatran etexilate were the least safe.
Recent studies have uncovered the vital roles played by microRNAs in regulating cardiac injury. Among them, the cardiac enriched microRNA-1 (miR-1) has been extensively studied and proven to be detrimental to cardiac myocytes. Hence, the current study aimed to explore whether miR-1 affects myocardial ischemia-reperfusion injury (MIRI) in rats undergoing sevoflurane preconditioning and the underlying mechanism. After successful model establishment, rats with MIRI were transfected with mimics or inhibitors of miR-1, or siRNA against MAPK3, and then were injected with sevoflurane. A luciferase reporter gene assay was conducted to evaluate the targeting relationship between miR-1 and MAPK3. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were employed to evaluate the expressions of miR-1, MAPK3, phosphatidylinositol 3-kinase (PI3K), and Akt. Additionally, the concentration of lactate dehydrogenase (LDH) was determined. Cell apoptosis and viability were assessed using TUNEL and cell counting kit-8 assays, and the ischemic area at risk and infarct size were detected using Evans blue and triphenyltetrazolium chloride staining. MAPK3 was found to be the target gene of miR-1. miR-1 expressed at a high level whereas MAPK3 expressed at a low level in MIRI rats. Overexpressing miR-1 or silencing MAPK3 blocked the PI3K/Akt pathway to increase cell apoptosis, ischemic area at risk, and infarct area but decreased cell viability and increased LDH concentration. In contrast, miR-1 downregulation abrogated the effects induced by miR-1 mimics or siRNA against MAPK3. These findings indicate that inhibition of miR-1 promotes MAPK3 to protect against MIRI in rats undergoing sevoflurane preconditioning through activation of the PI3K/Akt pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.