Bleeding and mortality risks after intravenous alteplase in stroke patients with prior dual antiplatelet therapy: a nationwide cohort study

Background The safety of intravenous alteplase, the standard thrombolytic therapy for acute ischemic stroke, in Asian patients receiving dual antiplatelet therapy (DAPT) prior to stroke remains uncertain, particularly with respect to bleeding and mortality risks. Purpose To evaluate bleeding and mortality risks following alteplase treatment for acute ischemic stroke among patients in Taiwan receiving DAPT prior to stroke compared with those receiving single or no antiplatelet therapy. Methods We conducted a nationwide population-based cohort study using Taiwan’s National Health Insurance Research Database (2011–2022). Adult patients hospitalized for acute ischemic stroke and treated with intravenous alteplase were identified. Antiplatelet exposure within 7 days before stroke was classified as DAPT, single antiplatelet therapy (SAPT), or no antiplatelet therapy. Propensity score matching was applied to balance baseline characteristics and reduce potential confounding. The primary outcome was intracranial hemorrhage during the index hospitalization following stroke and alteplase treatment. Secondary outcomes included major bleeding and in-hospital mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Results Among 9,264 alteplase-treated stroke patients, 280 (3.0%) had DAPT exposure prior to stroke, 2,239 (24.2%) had SAPT, and 6,745 (72.8%) had no antiplatelet therapy. In propensity score–matched analyses, DAPT prior to stroke was not associated with increased risks of intracranial hemorrhage (OR 0.69; 95% CI, 0.38–1.26), major bleeding (OR 0.75; 95% CI, 0.42–1.32), or in-hospital mortality (OR 1.06; 95% CI, 0.54–2.11) compared with no antiplatelet therapy. Risks were also similarly comparable between DAPT and SAPT groups. Findings were consistent across stratified analyses by age, sex, and stroke severity, and sensitivity analyses using multivariable adjustment and inverse probability of treatment weighting. Conclusions In this nationwide Taiwanese cohort of alteplase-treated stroke patients, DAPT exposure prior to stroke was not associated with increased bleeding or in-hospital mortality compared with single or no antiplatelet therapy. These findings suggest that bleeding and mortality outcomes following alteplase treatment may not differ by prior antiplatelet exposure and may inform clinical decision-making in Asian populations.