In STEMI patients with CHIP (VAF > 2%), ticagrelor reduced major adverse cardiovascular events by 58% compared to clopidogrel (HR 0.42, P=0.022).
Does ticagrelor reduce major adverse cardiovascular events compared to clopidogrel in STEMI patients with clonal hematopoiesis of intermediate potential (CHIP)?
In STEMI patients with clonal hematopoiesis of intermediate potential (CHIP), ticagrelor is associated with a significantly greater reduction in MACE compared to clopidogrel.
Abstract Background and Aims Clonal hematopoiesis of intermediate potential (CHIP) is a prominent risk factor for atherosclerosis, for which effective medications are still lacking. This study aimed to assess effects of P2Y12 inhibitors in the context of CHIP for patients with ST-segment elevation MI (STEMI). Methods A total of 1332 STEMI patients were prospectively recruited. CHIP was identified by any CHIP-gene mutations with variant allele frequency (VAF) ≥ 2%, 1% or 0.5% using targeted deep sequencing. Patients were stratified into four groups (figure 1) according to CHIP and P2Y12 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 (HF) and ischemic stroke. Results Overall, the average age for patients was 60.5 years old, and the majority of patients were male (81.3%). Defined by VAF2%, the prevalence of CHIP in the current cohort was 11.2%, and the most prevalent CHIP-mutation gene was DNMT3A (3.9%), followed by TET2 (2.9%), ASXL1 (1.4%), with the prevalence for other identified CHIP-mutation genes less than 1% (figure 1). The prevalence of CHIP mutations was 23.0% with VAF1%, and 45.4% with VAF0.5%, while the DNMT3A remained as the most prevalent mutated gene according to varying thresholds. The median follow-up was 1458 days. Compared to CHIP (VAF 2%) patients treated with clopidogrel (figure 2), CHIP patients receiving ticagrelor exhibited the lowest 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). Interactions were significant between ticagrelor and CHIP (P for interaction = 0.015, relative excess risk due to interaction: -1.53, 95% CI: -4.91－-0.66). Results remained consistent when CHIP was defined by VAF 1% or 0.5%. Conclusions CHIP and P2Y12 inhibitors jointly affected outcomes of STEMI patients, and ticagrelor associated to greater risk reduction in the presence of CHIP. These findings would promote more personalized anti-platelet medication for MI patients. Figure 1 Figure 2
Chen et al. (2025) studied this question. In STEMI patients with CHIP (VAF > 2%), ticagrelor reduced major adverse cardiovascular events by 58% compared to clopidogrel (HR 0.42, P=0.022).