Trick or Treat(ment): Should We Still Fear Reperfusion Therapy in Anticoagulated Stroke Patients?—Comparable 90-Day Outcomes in a Propensity-Score-Matched Registry Study

Background: The management of acute ischemic stroke (AIS) in anticoagulated patients presents a clinical challenge, as concerns about safety and efficacy often limit access to recanalization therapies. Despite the widespread use of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), their impact on functional recovery and mortality following intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) remains uncertain. Therefore, this study investigates the association between prior anticoagulation and 90-day outcomes in AIS patients undergoing reperfusion therapy. Methods: We conducted a retrospective cohort analysis using our institutional stroke registry, including AIS patients admitted to the Department of Neurology at our university between February 2023 and 2025. Anticoagulated patients were 1:1 propensity score-matched with non-anticoagulated controls (n = 126 per group) using Mahalanobis distance matching with a caliper, adjusting for age, sex, hypertension, diabetes, stroke severity (National Institutes of Health Stroke Scale [NIHSS] at admission and 72 h), and pre-stroke functional status (pre-morbid modified Rankin Scale [pre-mRS]). Primary endpoints at 90 days were functional independence (modified Rankin Scale [mRS] ≤ 2), mRS-shift, and mortality (mRS = 6). Predictors of outcome were assessed using multivariable logistic regression and generalized additive models (GAMs). Subgroup analyses evaluated the effects of anticoagulation type and treatment modality. Results: Among 866 AIS patients (DOAC n = 100, VKA n = 48, non-anticoagulated n = 718), 426 (49.2%) underwent reperfusion therapy (IVT n = 195, MT n = 163, IVT + MT n = 68). Before matching, anticoagulated patients were less likely to achieve functional independence (34.5% vs. 52.1%, odds ratio [OR] = 0.48, 95% confidence interval [CI] [0.33–0.70], p < 0.001), had a greater mRS-shift (2.53 vs. 1.79, p < 0.001), and higher mortality (30.4% vs. 14.5%, OR = 2.58, 95% CI [1.72–3.88], p < 0.001). However, after matching, these differences were no longer statistically significant. NIHSS, 72hNIHSS, and pre-mRS were the strongest independent predictors of outcome (p < 0.001), while anticoagulation status had no significant effect. Conclusions: Recanalization therapy was not associated with worse functional outcomes in selected anticoagulated AIS patients. These findings suggest that prior anticoagulation alone should not preclude reperfusion therapy in otherwise eligible patients, and underscore the importance of individualized, evidence-based decision-making in acute stroke care.