Combined effects of clonal hematopoiesis of intermediate potential and P2Y12 inhibitors on outcomes of patients with ST-segment elevation myocardial infarction: A prospective study

https://doi.org/10.1016/j.phrs.2025.107852

 Abstract

Clonal hematopoiesis of intermediate potential (CHIP) is a prominent risk factor for atherosclerosis, but effectivemedications for Clonal hematopoiesis of intermediate potential -associated risk are still lacking. This study aimed to assess prognostic impacts of P2Y12 inhibitors in the context of Clonal hematopoiesis of intermediate potential with aprospective cohort of 1332 patients of ST-segment elevation myocardial infarction (STEMI). Using targeted deep sequencing, Clonal hematopoiesis of intermediate potential was defined by any Clonal hematopoiesis of intermediatepotential -gene mutations with variant allele frequency (VAF) > 2%. Patients were stratified into four groups according to Clonal hematopoiesis of intermediate potential status and the prescribed types of P2Y12 inhibitors (ticagrelor and clopidogrel). The primary outcome was major adversecardiovascular events (MACE), a composite of death, recurrent MI, re-hospitalization due to heart failure and ischemic stroke. During a median follow-up of 1458 days, Clonal hematopoiesis of intermediate potential patientsreceiving ticagrelor exhibited lower risk of major adverse cardiovascular events (hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.20–0.88, P = 0.022), followed bynon- Clonal hematopoiesis of intermediate potential patients on clopidogrel (HR: 0.60, 95% CI: 0.41–0.88, P =0.010) and ticagrelor (HR: 0.66, 95% CI: 0.44–0.99, P = 0.044), as compared to Clonal hematopoiesis of intermediate potential patients on clopidogrel, with significantinteractions detected between ticagrelor and Clonal hematopoiesis of intermediate potential (P interaction =0.015, relative excess risk due to interaction: -1.53, 95% CI: -4.91– -0.66). In sum, Clonal hematopoiesis of intermediate potential and P2Y12 inhibitors jointly affected outcomes of STEMI patients, and ticagrelor was associated to greater risk reduction in the presence of Clonal hematopoiesis of intermediate potential. These findings would promote more personalized antiplatelet medications for patients with ST-segment elevation myocardial infarction.

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