P2Y12 Inhibitors Linked to Worse Intracerebral Hemorrhage Outcomes in Nationwide Study
Key Clinical Summary
- Patients receiving P2Y purinergic receptor 12 (P2Y12) inhibitors before spontaneous intracerebral hemorrhage (ICH) had higher odds of severe stroke, in-hospital mortality, and poorer functional outcomes than those receiving aspirin monotherapy.
- Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor plus aspirin was associated with the highest in-hospital mortality (24.0%), closely followed by P2Y12 inhibitor monotherapy (23.8%).
- Aspirin monotherapy showed no significant differences in adjusted in-hospital outcomes compared with no prior antiplatelet therapy.
A nationwide cohort study published in JAMA Network Open found that prior use of P2Y12 inhibitors, either alone or combined with aspirin, was associated with more severe presentation and worse hospital outcomes in patients with spontaneous ICH. The analysis used data from the Get With The Guidelines–Stroke registry and compared outcomes across different pre-ICH antiplatelet regimens in patients not receiving anticoagulation.
Study Findings
Investigators analyzed data from 252,691 patients hospitalized with spontaneous ICH. The cohort included 6355 patients (2.5%) receiving P2Y12 inhibitor monotherapy, 10 607 (4.2%) receiving DAPT, 63 299 (25.0%) receiving aspirin monotherapy, and 172 430 (68.2%) receiving no antiplatelet therapy within 7 days before hospital admission.
Patients receiving P2Y12 inhibitors were generally older and demonstrated a higher prevalence of cardiovascular risk factors. Severe stroke, defined as a National Institutes of Health Stroke Scale (NIHSS) score of 21 or higher, occurred in 26.8% of patients receiving P2Y12 inhibitor monotherapy and 25.3% of those receiving DAPT, compared with 20.5% of aspirin users and 23.2% of patients without prior antiplatelet therapy (P < .001).
Patients receiving DAPT demonstrated the highest in-hospital mortality rate (24.0%), followed by P2Y12 inhibitor monotherapy (23.8%), no antiplatelet therapy (16.8%), and aspirin monotherapy (16.5%) (P < .001).
When adjusted for risk, prior P2Y12 inhibitor use remained independently associated with severe stroke presentation (monotherapy: adjusted odds ratio [AOR], 1.43; 95% CI, 1.34–1.52; DAPT: AOR, 1.40; 95% CI, 1.33–1.47) and in-hospital mortality (monotherapy: AOR, 1.55; 95% CI, 1.46–1.66; DAPT: AOR, 1.61; 95% CI, 1.53–1.71) compared with aspirin monotherapy. Patients receiving P2Y12 inhibitors were also less likely to be discharged home, ambulate independently, or achieve functional independence at discharge.
No statistically significant differences in adjusted in-hospital outcomes were observed between aspirin monotherapy and no antiplatelet therapy.
Clinical Implications
The findings suggest that prior P2Y12 inhibitor therapy may identify patients at increased risk for severe presentation and poorer short-term outcomes after spontaneous ICH. Both P2Y12 inhibitor monotherapy and DAPT were consistently associated with higher odds of severe neurological deficits, increased in-hospital mortality, and reduced functional recovery compared with aspirin monotherapy.
For clinicians managing patients with atherosclerotic cardiovascular disease, these results provide important observational data regarding outcomes following spontaneous ICH in patients receiving different antiplatelet regimens. Although P2Y12 inhibitors are widely prescribed for cardiovascular indications, the study highlights the need to recognize their association with worse in-hospital outcomes should ICH occur.
The findings also reinforce the distinction between aspirin and P2Y12 inhibitors in this clinical setting. Aspirin monotherapy was not associated with significantly different adjusted in-hospital outcomes compared with no prior antiplatelet therapy, suggesting that the observed associations were specific to P2Y12 inhibitor exposure within this registry-based analysis.
Expert Commentary
“Despite advances in ICH management, the clinical outcomes remain poor, with 1 in 4 patients experiencing in-hospital death and 1 in 3 patients either dying or requiring hospice care at discharge,” wrote Chen Jin, MD, MSc, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and study coauthors. “These findings underscore the critical need to develop management strategies for this clinically challenging patient population.”
Reference
Jin C, Song Y, Mac Grory B, et al. P2Y12 inhibitors and mortality in patients hospitalized with intracerebral hemorrhage. JAMA Netw Open. 2026;9(7):e2622239. doi:10.1001/jamanetworkopen.2026.22239
