Differential prognostic significance of platelet reactivity based on ischemic risk after percutaneous coronary intervention

Abstract Background High platelet reactivity (HPR) in patients underwent percutaneous coronary intervention (PCI) is a potential risk factor of adverse cardiovascular events. It is not well understood in which patients HPR is particularly clinically important. Purpose We aimed to elucidate the prognostic value of high platelet reactivity (HPR), across varying levels of ischemic risk categorized by the CHADS-P2A2RC score in a large registry. Methods We retrospectively analyzed 11,714 patients who underwent PCI in the PTRG-DES registry. Ischemic risk was stratified using the CHADS-P2A2RC score into low (score ≤ 1), moderate (score 2–3), and high (score ≥ 4) groups. HPR was defined as a P2Y12 Reaction Unit (PRU) value ≥252. The incidence of major adverse cardiac and cerebrovascular events (MACCE) during 5- year follow-up was the primary outcome. Results During the median follow-up of 37.6 months (IQR, 12.0–60.8), a total of 709 MACCEs (6.1%) (392 deaths [3.3%], 172 non-fatal MI [1.5%], 62 ST [0.5%] and 181 non-fatal stroke [1.5%]), and 324 cases of major bleeding (2.8%) occurred. The high-risk group has the highest incidence of MACCE during 5-year follow-up unadjusted HR of 4.206, 95% CI 3.204–5.521. Among the 2,577 low-risk patients, HPR did not significantly affect MACCE incidence (HR 1.366, 95% CI 0.798–2.336, p=0.253). In the moderate-risk cohort of 5,417 patients, HPR conferred a modest increase in MACCE risk (HR 1.289, 95% CI 1.008–1.649, p=0.043). Notably, the high-risk group demonstrated a significant association between HPR and MACCE (HR 1.385, 95% CI 1.135–1.692, p<0.001). Conclusion HPR is a potent risk factor of long-term outcomes following PCI, especially in patients with a high ischemic risk based on CHADS-P2A2RC scoring. The results highlight the varying impact of platelet reactivity depending on the level of ischemic risk, indicating the importance of tailored antiplatelet therapy in high-risk group to improve clinical outcomes.