Antithrombotic Strategy After Transcatheter Aortic Valve Replacement: A Network Meta-Analysis.

The ideal antithrombotic therapy post transcatheter aortic valve replacement (TAVR) remains uncertain. We performed a network meta-analysis of RCTs to report the outcomes with various antithrombotic strategies to determine the optimal therapy. A systematic search of the PubMed/Medline and Cochrane databases was performed through January 6, 2022. The primary outcome was stroke and the secondary outcomes were major/life-threatening bleeding, myocardial infarction, all-cause mortality, and cardiac mortality. A network meta-analysis was conducted with a random-effects model. All analysis was carried out using R version 4.0.3. Six RCTs were included in the final analysis. SAPT when compared with DAPT was associated with a reduced risk of major or life-threatening bleeding [OR: 0.42; 95% CI: 0.25-0.70]. Other antithrombotic strategies were associated with similar odds of major and life-threatening bleeding post TAVR compared with DAPT. There was no difference in the incidence of stroke, myocardial infarction, all-cause and cardiac mortality between the various antithrombotic strategies post TAVR. The present analysis reported SAPT as the preferred antithrombotic regimen post TAVR compared with other regimens in patients who do not have other indications for anticoagulation. Additional studies such as ADAPT-TAVR, CLOE and ATLANTIS trials will further add to our understanding of the adequate antithrombotic regimen post TAVR in patients with otherwise no indication for anticoagulation.

miR-467 regulates inflammation and blood insulin and glucose.

Obesity is associated with inflammation and insulin resistance (IR), but the regulation of insulin sensitivity (IS) and connections between IS and inflammation remain unclear. We investigated the role of miR-467a-5p, a miRNA induced by hyperglycaemia, in regulating inflammation and blood glucose handling. We previously demonstrated that miR-467a-5p is induced by hyperglycaemia and inhibits the production of thrombospondin-1 (TSP-1), a protein implicated in regulating inflammation. To investigate the role of miR-467 in blood glucose handling and tissue inflammation, WT C57BL/6 mice were fed chow or Western diet from 5 to 32 weeks of age and injected weekly with miR-467a-5p antagonist. Inhibiting miR-467a-5p resulted in 47% increase in macrophage infiltration and increased Il6 levels in adipose tissue, higher plasma insulin levels (98 ng/mL vs 63 ng/mL), and 17% decrease in glucose clearance without increase in weight or HDL/LDL. The antagonist effect was lost in mice on Western diet. Mice lacking TSP-1 lost some but not all of the miR-467 effects, suggesting Thbs1 (and other unknown transcripts) are targeted by miR-467 to regulate inflammation. miR-467a-5p provides a physiological feedback when blood glucose is elevated to avoid inflammation and increased blood glucose and insulin levels, which may prevent IR.