Design and rationale for REVERXaL: A real-world study of patients with factor Xa inhibitor-associated major bleeds.

BACKGROUND: The prevalence of anticoagulation treatment is increasing as an aging global population faces a high burden of cardiovascular comorbidities. Direct oral anticoagulants, including factor Xa inhibitors (FXai), are replacing vitamin K antagonists as the most commonly prescribed treatment for reducing risk of thrombotic events. While the risk of FXai-associated spontaneous bleeds is established, less is understood about their management and the effect of treatment on clinical and patient-reported outcomes. The primary objectives of the REVERXaL study are to describe patient characteristics, health care interventions during the acute-care phase, in-hospital outcomes, and associations between timing of reversal/replacement agent administration and in-hospital outcomes. Secondary/exploratory objectives focus on clinical assessments and patient-reported outcome measures (PROMs) at 30 and 90 days. METHODS: REVERXaL is a multinational, observational study of hospitalized patients with FXai-associated major bleeds in Germany, Japan, the United Kingdom, and the United States. The study includes 2 cohorts of approximately 2000 patients each. Cohort A is a historic cohort for whom medical chart data will be collected from hospitalization to discharge for patients admitted for major bleeds during FXai use within 2 years prior to enrollment of Cohort B. Cohort B will prospectively enroll patients administered any reversal/replacement agent during hospitalization to manage FXai-associated major bleeds and will include the collection of clinical outcomes and PROMs data over 3 months. CONCLUSIONS: REVERXaL will generate insights on patient characteristics, treatment approaches, and associated outcomes in patients hospitalized with FXai-associated major bleeds. These data may inform clinical practice and streamline treatment pathways in this population. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; unique identifier: NCT06147830.

Using 30-day modified rankin scale score to predict 90-day score in patients with intracranial hemorrhage: Derivation and validation of prediction model.

Whether 30-day modified Rankin Scale (mRS) scores can predict 90-day scores is unclear. This study derived and validated a model to predict ordinal 90-day mRS score in an intracerebral hemorrhage (ICH) population using 30-day mRS values and routinely available baseline variables. Adults enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) trial between May 2011 and September 2015 with acute ICH, who were alive at 30 days and had mRS scores reported at both 30 and 90 days were included in this post-hoc analysis. A proportional odds regression model for predicting ordinal 90-day mRS scores was developed and internally validated using bootstrapping. Variables in the model included: mRS score at 30 days, age (years), hematoma volume (cm3), hematoma location (deep [basal ganglia, thalamus], lobar, or infratentorial), presence of intraventricular hemorrhage (IVH), baseline Glasgow Coma Scale (GCS) score, and National Institutes of Health Stroke Scale (NIHSS) score at randomization. We assessed model fit, calibration, discrimination, and agreement (ordinal, dichotomized functional independence), and EuroQol-5D ([EQ-5D] utility weighted) between predicted and observed 90-day mRS. A total of 898/1000 participants were included. Following bootstrap internal validation, our model (calibration slope = 0.967) had an optimism-corrected c-index of 0.884 (95% CI = 0.873-0.896) and R2 = 0.712 for 90-day mRS score. The weighted ĸ for agreement between observed and predicted ordinal 90-day mRS score was 0.811 (95% CI = 0.787-0.834). Agreement between observed and predicted functional independence (mRS score of 0-2) at 90 days was 74.3% (95% CI = 69.9-78.7%). The mean ± SD absolute difference between predicted and observed EQ-5D-weighted mRS score was negligible (0.005 ± 0.145). This tool allows practitioners and researchers to utilize clinically available information along with the mRS score 30 days after ICH to reliably predict the mRS score at 90 days.

Agreement between 30-day and 90-day modified Rankin Scale score and utility-weighted modified Rankin Scale score in acute intracerebral hemorrhage: An analysis of ATACH-2 trial data.

The relationship between 30- and 90-day modified Rankin Scale (mRS) scores in intracerebral hemorrhage (ICH) patients was evaluated. This post hoc cohort analysis of the ATACH-2 trial included patients with acute ICH who were alive at 30 days and who had mRS scores reported at 30 and 90 days. The mRS score was then converted to a utility (EuroQol-5 Dimension-3 Level [EQ-5D-3L])-weighted mRS score. After adjustment of 30-day mRS score for key covariates using multivariable ordinal regression, the relationship between 30-day and observed 90-day functional outcome was assessed via absolute difference in the utility-weighted version. Of the 1000 trial subjects, 898 met inclusion criteria. This low-moderate severity ICH cohort had a median baseline GCS score of 15 and median hematoma volume of 9.7 mL. Observed 30-day mRS had the largest association with observed 90-day values (χ2 = 302.9, p < 0.0001). Patients generally either maintained the same mRS scores between 30 and 90 days (48 %) or experienced a 1-point (32 %) or 2-point (10 %) improvement by 90 days. The mean ± standard deviation (SD) EQ-5D-3L at 90 days was 0.67 ± 0.26. Following adjustment, the mean absolute difference between predicted and observed utility-weighted 90-day mRS scores was 0.006 ± 0.13 points and less than the estimated minimal clinically important difference of 0.13 points. The difference in average utility-weighted mRS scores at 30 and 90 days was not clinically relevant, suggesting 30-day score may be a reasonable proxy for 90-day values in patients with ICH when 90-day values are not available.