Effect of Intravenous Alteplase on Functional Outcome and Secondary Injury Volumes in Stroke Patients with Complete Endovascular Recanalization

Intravenous thrombolytic therapy with alteplase (IVT) is a standard of care in ischemic stroke, while recent trials investigating direct endovascular thrombectomy (EVT) approaches showed conflicting results. Yet, the effect of IVT on secondary injury volumes in patients with complete recanalization has not been analyzed. We hypothesized that IVT is associated with worse functional outcome and aggravated secondary injury volumes when administered to patients who subsequently attained complete reperfusion after EVT. Anterior circulation ischemic stroke patients with complete reperfusion after thrombectomy defined as thrombolysis in cerebral infarctions (TICI) scale 3 after thrombectomy admitted between January 2013–January 2021 were analyzed. Primary endpoints were the proportion of patients with functional independence defined as modified Rankin Scale (mRS) score 0–2 at day 90, and secondary injury volumes: Edema volume in follow-up imaging measured using quantitative net water uptake (NWU), and the rate of symptomatic intracerebral hemorrhage (sICH). A total of 219 patients were included and 128 (58%) patients received bridging IVT before thrombectomy. The proportion of patients with functional independence was 28% for patients with bridging IVT, and 34% for patients with direct thrombectomy (p = 0.35). The rate of sICH was significantly higher after bridging IVT (20% versus 7.7%, p = 0.01). Multivariable logistic and linear regression analysis confirmed the independent association of bridging IVT with sICH (aOR: 2.78, 95% CI: 1.02–7.56, p = 0.046), and edema volume (aOR: 8.70, 95% CI: 2.57–14.85, p = 0.006). Bridging IVT was associated with increased edema volume and risk for sICH as secondary injury volumes. The results of this study encourage direct EVT approaches, particularly in patients with higher likelihood of successful EVT

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

ObjectivesAmong patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant.DesignSecondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).SettingOne hundred-fifty-three ICUs in 13 countries.PatientsAltogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).InterventionsNone.Measurements and main resultsTotal mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p p p p p p p p = 0.007).ConclusionsAmong STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions