P2RY12 rs10755105 T/C carriers had a lower risk of MACE (HR 0.57; 95% CI 0.42-0.79) but higher bleeding risk compared to C/C carriers in STEMI patients receiving ticagrelor.
Cohort (n=1,828)
Does P2RY12 polymorphism and expression impact the risk of MACE and bleeding in STEMI patients treated with ticagrelor?
P2RY12 polymorphism rs10755105 and expression scores demonstrate opposing effects on ischemic and bleeding risks in STEMI patients on ticagrelor, suggesting a potential role for genetic-based risk stratification.
Effect estimate: HR 0.57 (95% CI 0.42-0.79)
BACKGROUND: The influence of P2RY12 polymorphisms and expression on the ischemia-bleeding balance in patients with ST-segment elevation myocardial infarction (STEMI) remains poorly defined. OBJECTIVES: To evaluate the associations of P2RY12 with major adverse cardiovascular events (MACE) and bleeding risk in STEMI patients treated with ticagrelor. METHODS: This prospective cohort study enrolled patients with STEMI who underwent percutaneous coronary intervention and received ticagrelor therapy between 2018 and 2020. The main outcomes were MACEs and bleeding events within 2 years. A Cox model was used to examine the effects of P2RY12 polymorphisms on both events. Additionally, the P2RY12 expression scores were constructed to further evaluate the association between its expression levels and both events. RESULTS: A total of 1828 STEMI patients were included, with 194 MACE (10.61%) and 237 bleeding events (12.96%) recorded. Compared with the rs10755105 C/C, the MACE hazard ratios (HRs) (95% CI) of T/C and T/T carriers were 0.57 (0.42-0.79) and 0.67 (0.45-1.00), respectively, while for bleeding, they were 1.35 (0.99-1.85) and 1.53 (1.06-2.20), respectively. P2RY12 expression scores showed a U-shaped relationship with MACE risk and an inverse U-shaped association with bleeding (P CONCLUSION: Both rs10755105 and the P2RY12 expression score show opposing effects on ischemic and bleeding risks. The identified non-linear relationships provide novel insights for refined risk stratification in STEMI.
Li et al. (Sun,) conducted a cohort in ST-segment elevation myocardial infarction (STEMI) (n=1,828). P2RY12 rs10755105 T/C and T/T polymorphisms vs. P2RY12 rs10755105 C/C polymorphism was evaluated on Major adverse cardiovascular events (MACE) (HR 0.57, 95% CI 0.42-0.79). P2RY12 rs10755105 T/C carriers had a lower risk of MACE (HR 0.57; 95% CI 0.42-0.79) but higher bleeding risk compared to C/C carriers in STEMI patients receiving ticagrelor.