Association between clinical ischemic risk and thrombogenicity phenotype and their prognostic prediction in patients undergoing percutaneous coronary intervention

Abstract Introduction The CHADS-P2A2RC score has been developed to provide better prognostic precision and improved selection of at-risk patients with coronary artery disease (CAD). The linkage of this clinical ischemic risk with thrombogenicity and their prognostic implication remain still unknown. Purpose We investigated the values of thrombogenicity indices according to the CHADS-P2A2RC score and their combined prognostic prediction in CAD patients undergoing percutaneous coronary intervention (PCI). Methods In PCI-treated patients (PCI) (n=2,705), clinical ischemic risk was classified with CHADS-P2A2RC score ("high risk": ≥ 4) and thrombogenicity indices were assessed using thromboelastography (TEG). Major adverse cardiovascular events (MACEs: a composite of all-cause death, myocardial infarction, or stroke) and major bleeding were evaluated were monitored for up to 3 years. Results Compared with "low/moderate-risk group" (67.7%), "high-risk group" (32.3%) had higher platelet-fibrin clot strength (PFCS: 67.3±7.9 vs. 65.2±7.2 mm; P < 0.001) and lower fibrinolytic activity (clot lysis at 30 min [LY30]: 0.9±2.1% vs. 1.1±2.4%, P < 0.001]. The "high-risk group" showed higher rates of "high PFCS phenotype (≥ 68 mm)" (35.3% vs. 49.7%; P <0.001), MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; P = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; P = 0.013) than the "low/moderate-risk group", respectively. Among the "low/moderate-risk group", "high MA phenotype" independently predicted MACE (HRadjusted: 1.51; 95% CI: 1.00-2.27; P = 0.048) and all-cause mortality (HRadjusted: 1.90; 95% CI: 1.06-3.4; P = 0.031). Likewise, this phenotype increased the risks of MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; p = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; p = 0.013) in the "high-risk group" (Table 1 and Figure 1). Prognostic impact of "high MA phenotype" on major bleeding was not significantly different across the risk-group (HRadjusted: 1.02; 95% CI: 0.39-2.72; P = 0.963 in the "low/moderate-risk group" and HRadjusted: 1.08; 95% CI: 0.50-2.34; P = 0.884 in the "high-risk group", respectively). Conclusion In PCI-treated patients, CHADS-P2A2RC score was significantly associated with a worse clinical outcome and more thrombogenic profile. Regardless of the ischemic-risk group, the level of clot-strength had an addictive effect on predicting the risk of ischemic event, indicating assessment of thrombogenicity indices using TEG may enhance post-PCI risk stratification for personalized antithrombotic therapy.