Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage

Abstract

ImportanceIntracerebral hemorrhage (ICH) is the deadliest stroke subtype, and mortality rates are especially high in anticoagulation-associated ICH. Recently, specific anticoagulation reversal strategies have been developed, but it is not clear whether there is a time-dependent treatment effect for door-to-treatment (DTT) times in clinical practice.ObjectiveTo evaluate whether DTT time is associated with outcome among patients with anticoagulation-associated ICH treated with reversal interventions.Design, Setting, and ParticipantsThis cohort study used data from the American Heart Association Get With The Guidelines–Stroke quality improvement registry. Patients with ICH who presented within 24 hours of symptom onset across 465 US hospitals from 2015 to 2021 were included. Data were analyzed from January to September 2023.ExposuresAnticoagulation-associated ICH.Main Outcomes and MeasuresDTT times and outcomes were analyzed using logistic regression modeling, adjusted for demographic, history, baseline, and hospital characteristics, with hospital-specific random intercepts to account for clustering by site. The primary outcome of interest was the composite inpatient mortality and discharge to hospice. Additional prespecified secondary outcomes, including functional outcome (discharge modified Rankin Scale score, ambulatory status, and discharge venue), were also examined.ResultsOf 9492 patients with anticoagulation-associated ICH and documented reversal intervention status, 4232 (44.6%) were female, and the median (IQR) age was 77 (68-84) years. A total of 7469 (78.7%) received reversal therapy, including 4616 of 5429 (85.0%) taking warfarin and 2856 of 4069 (70.2%) taking a non–vitamin K antagonist oral anticoagulant. For the 5224 patients taking a reversal intervention with documented workflow times, the median (IQR) onset-to-treatment time was 232 (142-482) minutes and the median (IQR) DTT time was 82 (58-117) minutes, with a DTT time of 60 minutes or less in 1449 (27.7%). A DTT time of 60 minutes or less was associated with decreased mortality and discharge to hospice (adjusted odds ratio, 0.82; 95% CI, 0.69-0.99) but no difference in functional outcome (ie, a modified Rankin Scale score of 0 to 3; adjusted odds ratio, 0.91; 95% CI, 0.67-1.24). Factors associated with a DTT time of 60 minutes or less included White race, higher systolic blood pressure, and lower stroke severity.Conclusions and RelevanceIn US hospitals participating in Get With The Guidelines–Stroke, earlier anticoagulation reversal was associated with improved survival for patients with ICH. These findings support intensive efforts to accelerate evaluation and treatment for patients with this devastating form of stroke.

Door-in-Door-Out Times at Referring Hospitals and Outcomes from Hemorrhagic Stroke

“…24 One potential explanation for these findings in RACECAT was patients with ICH transferred to EVT-capable stroke centers may have had delayed emergency stabilization and ICH "bundle of care" measures as compared to patients directly transported to local stroke centers. Results from INTERACT3 7 and other literature 25 have recently demonstrated that early bundled care for ICH, including antithrombotic reversal, 8 appropriate management of blood pressure, hyperglycemia and pyrexia led to improved functional outcomes. 7 While we were unable to measure the presence or absence of ICH care bundles in the current study, one interpretation of our findings is that longer DIDO times at transferring facilities may have afforded more adequate time for emergency stabilization measures, which could have translated into better outcomes from ICH and SAH.…”

“…Model covariates with missing data were imputed before entering into models following previous GWTG-stroke studies. 8,21 Observations with >25% missing were excluded and missing medical history values and medications prior to admission were imputed to “No”. Insurance status for patients 65 years or older was imputed to “Medicare” and all other patients were imputed to “Private / VA / Champus / Other Insurance”.…”

“…7 A recent study from the Get With the Guidelines (GWTG)-Stroke registry demonstrated an association between earlier anticoagulation reversal and improved survival from ICH. 8 Additionally, a 2024 systematic review from the Blood Pressure in Acute Stroke Collaboration showed a clear time relation between early vs late blood pressure control in ICH patients with improvement in functional outcomes and a lower risk of hematoma expansion. 4 Ongoing efforts including the recent consensus statement for "Code ICH" emphasize the importance of early bundled care for ICH and adherence to time-based metrics, 9 which could change the landscape of care for hemorrhagic stroke.…”