P2Y12 Inhibitors and Mortality in Patients Hospitalized With Intracerebral Hemorrhage.

Importance: Although P2Y purinergic receptor 12 (P2Y12) inhibitors are commonly used in patients with atherosclerotic cardiovascular disease, there are limited data on intracerebral hemorrhage (ICH) associated with use of P2Y12 inhibitors. Objective: To compare stroke severity, in-hospital mortality, and functional outcomes in ICH among patients receiving P2Y12 inhibitor monotherapy, dual antiplatelet therapy (DAPT) with P2Y12 inhibitor plus aspirin, aspirin monotherapy, or no antiplatelet therapy prior to ICH. Design, Setting, and Participants: This cohort study obtained data from the nationwide Get With The Guidelines-Stroke registry, which contains data from participating hospitals. Participants were patients hospitalized with spontaneous ICH between January 2013 to December 2021. The analysis was completed in January 2025. Exposures: Antiplatelet therapy before ICH, defined as any use within 7 days prior to hospital arrival. Main Outcomes and Measures: The primary outcomes were severe stroke at presentation and in-hospital mortality. Severity was assessed using the National Institutes of Health Stroke Scale (NIHSS; range: 0-42, with higher scores indicating greater severity), with a score of 21 or higher indicating severe stroke. Secondary outcomes included in-hospital mortality or discharge to hospice, discharge to home, independent ambulation, and modified Rankin Scale (mRS) score at discharge. An mRS score of 0 to 2 at discharge indicated functional independence. Results: Of the 252 691 patients included (median [IQR] age, 67 [56-78] years; 134 684 males [53.3%]), 6355 (2.5%) were receiving P2Y12 inhibitor monotherapy, 10 607 (4.2%) were receiving DAPT, 63 299 (25.0%) were receiving aspirin monotherapy, and 172 430 (68.2%) were receiving no antiplatelet agents prior to ICH. Patients taking P2Y12 inhibitors were older and had higher prevalence of cardiovascular risk factors. Overall, 1701 patients (26.8%) receiving P2Y12 monotherapy and 2688 patients (25.3%) receiving DAPT experienced severe ICH (NIHSS score ≥21) compared with 12 952 patients (20.5%) who used aspirin monotherapy and 39 970 (23.2%) patients who received no antiplatelet (P < .001). In-hospital mortality rates were highest in patients using DAPT (24.0%), followed by patients receiving P2Y12 inhibitor monotherapy (23.8%), no antiplatelet (16.8%), and aspirin monotherapy (16.5%) (P < .001). After risk adjustment, patients with prior use of P2Y12 inhibitors were more likely to present with severe stroke (P2Y12 inhibitor monotherapy: adjusted odds ratio [AOR], 1.43 [95% CI, 1.34-1.52]; P < .001; DAPT: AOR, 1.40 [95% CI, 1.33-1.47]; P < .001) and more likely to die in the hospital (P2Y12 inhibitor monotherapy: AOR, 1.55 [95% CI, 1.46-1.66]; P < .001; DAPT: AOR, 1.61 [95% CI, 1.53-1.71]; P < .001) compared with those using aspirin monotherapy. Furthermore, these patients were less likely to be discharged to home, be able to ambulate independently, or have functional independence at discharge. In contrast, there were no statistically significant differences in in-hospital outcomes between aspirin monotherapy and no antiplatelet therapy groups. Conclusions and Relevance: In this registry-based cohort study of patients with ICH not associated with anticoagulation, P2Y12 inhibitors, either as monotherapy or in combination with aspirin, were associated with more severe stroke, in-hospital death, worse clinical outcomes, and reduced functional recovery compared with aspirin monotherapy or no antiplatelet therapy.