Intracerebral Hemorrhage Outcomes After Reversal of Subtherapeutic Warfarin: Analysis of Data From GWTG-Stroke.

Background: Current guidelines recommend reversal of warfarin anticoagulation in intracranial hemorrhages. The benefit of reversing subtherapeutic warfarin anticoagulation in acute spontaneous intracerebral hemorrhage is uncertain.

Methods: An observational cohort from the entire Get With The Guidelines Stroke registry between January 2015 and January 2022 was used to determine the association of reversal with outcomes for subtherapeutic anticoagulation (international normalized ratio, 1.5-1.9). Inclusion required current warfarin use. Exclusions included thrombolytics, direct oral anticoagulants, transferring out, or leaving against medical advice. The prespecified primary outcome was the modified Rankin Scale (mRS) score of 0 to 3 at discharge. Logistic regression was used to assess the association between reversal and the mRS score of 0 to 3. Propensity scores with overlap weighting were used to control treatment selection bias. Information on the dose and timing of reversal agents was unknown.

Results: Initial cohort 239 681 patients, 18 419 on warfarin. Excluded were 15 712 with an international normalized ratio ≤1.5, ≥1.9, or missing, and 701 missing mRS. Final cohort 1868 (mean age 73, 42% female). Reversal occurred in 894 (47.9%). Primary outcome occurred in 188/894 (21.0%) versus 225/974 (23.1%) with reversal versus without (adjusted odds ratio, 0.80 [95% CI, 0.63-1.005]). Ordinal analysis showed higher odds of mRS score of 0 to 4 versus 5 to 6 (52.7% versus 42.5% [adjusted odds ratio, 1.21 [1.001-1.48]). Outcomes not requiring mRS were analyzed among 2569 patients. Mortality or discharge to hospice was lower 30.6% versus 41.5% (adjusted odds ratio, 0.75 [95% CI, 0.63-0.89]). Hospital length of stay was longer (median, 6 versus 4 days; adjusted risk ratio, 1.25 [95% CI, 1.13-1.37]). There was no difference in venous thromboembolism (2.9% versus 2.3%; adjusted odds ratio, 1.47 [0.88-2.46]).

Conclusions: Reversal of subtherapeutic warfarin with acute spontaneous intracerebral hemorrhage and international normalized ratio 1.5 to 1.9 was not associated with improvement in functional outcome based on discharge mRS score of 0 to 3 versus 4 to 6. Patients receiving reversal agents had 25% lower odds of dying in hospital or being discharged to hospice, but had a longer hospital stay. This exploratory data has limitations inherent to not being a randomized controlled trial.