The STARTING-SICH is the first nomogram developed and validated in a large SITS-ISTR cohort for individualized prediction of sICH in intravenous thrombolysis-treated stroke patients.

ImportanceInternational guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC).ObjectiveTo determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion.Design, Setting, and ParticipantsThis international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021.ExposuresPrior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation.Main Outcomes and MeasuresThe main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses.ResultsOf 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion.Conclusions and RelevanceIn this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

Background and purpose The nomogram is an important component of modern medical decision-making, which calculates the probability of an event entirely based on individual characteristics. We aimed to develop and validate a nomogram for individualized prediction of the probability of unfavorable outcome in intravenous thrombolysis-treated stroke patients included in the large multicenter Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. Methods All patients registered in the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register by 179 Italian centers between May 2001 and March 2016 were originally included. The main outcome measure was three-month unfavorable outcome (modified Rankin Scale 3-6). Four non-categorical predictors of unfavorable outcome (baseline National Institutes of Health (NIH) Stroke Scale score: 0-25, age ≥18 years, pre-stroke modified Rankin Scale score: 0-2, and onset-to-treatment time: 0-270 min) were identified a-priori by three neurologists with expertise in the management of stroke. To generate the NIHSS STroke Scale score, Age, pre-stroke mRS score, onset-to-treatment Time (START), the pre-established predictors were entered into a logistic regression model. The discriminative performance of the model was assessed using the area under the receiver operating characteristic curve. Results A total of 15,862 patients with complete data for generating the START was randomly dichotomized into training (2/3, n = 10,574) and test (1/3, n = 5288) sets. The area under the receiver operating characteristic curve of START was 0.800 (95% confidence interval: 0.792-0.809) in the training set and 0.815 (95% confidence interval: 0.804-0.822) in the test set. Conclusions By using a limited number of non-categorical predictors, the START is the first nomogram developed and validated in a large Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register cohort, which reliably calculates the probability of unfavorable outcome in intravenous thrombolysis-treated stroke patients.