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

Clonal hematopoiesis of intermediate potential (CHIP) is a prominent risk factor for atherosclerosis, but effective medications for CHIP-associated risk are still lacking. This study aimed to assess prognostic impacts of P2Y 12 inhibitors in the context of CHIP with a prospective cohort of 1332 patients of ST-segment elevation myocardial infarction (STEMI). Using targeted deep sequencing, CHIP was defined by any CHIP-gene mutations with variant allele frequency (VAF) > 2%. Patients were stratified into four groups according to CHIP status and the prescribed types of P2Y 12 inhibitors (ticagrelor and clopidogrel). The primary outcome was major adverse cardiovascular 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, CHIP patients receiving ticagrelor exhibited lower risk of MACE (hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.20–0.88, P = 0.022), followed by non-CHIP 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 CHIP patients on clopidogrel, with significant interactions detected between ticagrelor and CHIP (P interaction = 0.015, relative excess risk due to interaction: -1.53, 95% CI: -4.91– -0.66). In sum, CHIP and P2Y 12 inhibitors jointly affected outcomes of STEMI patients, and ticagrelor was associated to greater risk reduction in the presence of CHIP. These findings would promote more personalized antiplatelet medications for patients with STEMI.