URL: https://www.clinicaltrials.gov. Unique identifier: NCT02126085.

Background and purpose Trimethylamine‐N‐oxide (TMAO) is a biomarker of the gut microbiome and correlates with the risk of cardiovascular diseases. However, conflicting data exist on the specific role of TMAO in ischaemic stroke patients. We aimed to analyze the time course of TMAO levels in stroke patients compared with controls. Methods In this prospective, case‐control study, patients suffering from ischaemic stroke (onset <24 h) and control patients with less than two cardiovascular risk factors were enrolled. Plasma TMAO levels were analyzed on admission, after 48 h and after 3 months. The primary endpoint was the difference in TMAO levels on admission between stroke patients and controls. Results A total of 196 patients with ischaemic stroke and 100 controls were included between February 2018 and April 2019. Plasma TMAO levels on admission were significantly higher in stroke patients than in controls [median value 4.09 (2.87–6.49) vs. 3.16 (2.08–5.16) µmol/L, P = 0.001]. There was a significant decrease in TMAO levels in stroke patients after 48 h [median at 48 h, 3.49 (2.30–5.39) µmol/L, P = 0.027]. TMAO levels increased again 3 months after stroke [median 4.23 (2.92–8.13) µmol/L, P = 0.047]. In controls, TMAO levels did not change between admission and after 48 h [median at 48 h, 3.14 (1.63–4.61) µmol/L, P = 0.11]. An inverse correlation between TMAO values and kidney function was found (Spearman rho −0.334, P < 0.001). Conclusions Our study emphasizes the importance of the time course of TMAO levels after ischaemic stroke. Future studies should define the time point of TMAO analysis, preferably in the acute phase (<24 h).

BackgroundIt is common practice to withhold IV thrombolysis (IVT) for acute ischemic stroke in patients with preexisting disabilities. To test the hypothesis of an association of IVT and good clinical outcome also in patients with preexisting disabilities without an increase in mortality, we analyzed data from 52,741 patients (15,317 treated with IVT) depending on prestroke Rankin Scale (pRS) score.MethodsWe performed an observational study based on a consecutive stroke registry covering 10.8 million inhabitants. The outcome at discharge of patients with stroke admitted in the time window of potential eligibility for IVT (<4.5 hours after stroke onset) was compared between patients treated and those not treated with thrombolysis, stratified by pRS score. Logistic regression analysis was used to estimate adjusted odds ratios (ORs) along with 95% confidence intervals (CIs) for favorable clinical outcome, defined as returning to the baseline pRS score or a score of 0 or 1 and mortality. Sensitivity analyses for subgroups of mildly and severely affected patients with stroke were performed, and the influence of treatment duration was assessed.ResultsAmong included patients, IVT rates were 32% for patients with pRS scores of 0 to 1 and 20% for patients with pRS scores of 2 to 5. IVT in patients with pRS scores of 0 to 4 was associated with a higher chance of returning to the baseline pRS score (or a modified Rankin Scale score of 0/1), with ORs ranging between 1.42 (pRS score 2; 95% CI 1.16–1.73) and 1.73 (pRS score 0; 95% CI 1.61–1). The OR observed in patients with a pRS score of 5 was 0.65 (95% CI 0.25–1.70). Observed associations remained consistent in sensitivity analyses. Subgroup analyses revealed no evidence of bias due to potential floor and ceiling effects. No evidence of elevated in-hospital mortality of patients treated with thrombolysis was observed.ConclusionsOur study suggests that IVT can be effective even in patients with severe preexisting disabilities, provided that they were not bedridden before stroke onset. Withholding IVT on the sole ground of prestroke disabilities may not be justified.

No abstract