Prognostic Triad Determining Outcome after PCI: Diabetes Mellitus, High Residual Platelet Reactivity and Endothelial Dysfunction

Objective: The present study was designed to evaluate the prognostic value of platelet reactivity, initial level of inflammation markers and endothelial dysfunction, as well as CYP2C19*2 allele carriage in clinical outcome after percutaneous coronary interventions (PCI) in patients with stable coronary artery disease (SCAD) on dual antiplatelet therapy (DAPT).
Methods: A prospective, single-center study included 94 patients with SCAD who underwent PCI with DES implantation, 20% had diabetes mellitus. Platelet reactivity was determined in all patients using light transmission aggregometry induced with 5μmol/L ADP (LTA-ADP) and VerifyNow before PCI, as well as CYP2C19 genotyping. In 74 patients were determined baseline levels of high-sensitivity C-reactive protein, soluble P-selectin, soluble CD40 ligand, highly sensitive IL-6, plasminogen activator inhibitor-1 levels and von Willebrand factor activity. Mean follow-up period was 28,2±15,5 months. Cumulative endpoint included major adverse cardiac event, stent thrombosis, angina recurrence or angiographically confirmed restenosis.
Results: According to univariate regression analysis we revealed that diabetes mellitus [exp (B) 0,344 95% CI 0,118-1,004, p=0,049], PRU [exp (B) 1,009; 95% CI 1,002-1,017, p=0.01], number of stented arteries [exp (B) 4,00; 95% CI 1,475-10,848, p=0.01], number of implanted stents [exp (B) 3,672; 95% CI 1,366-9,872, p=0.01], baseline levels of PAI-1 [exp (B) 1,000, 95% CI 0,999-1,000, p=0.03] and von Willebrand activity [exp (B) 1,000, 95 1,000-1,000% CI, p=0.01]. The presence of CYP2C19*2 carriers revealed no significant impact on outcome after PCI. Using ROC-curve analysis to determine cutoff values for PRU was 202 (AUC 0,664; 95%CI 0,531-0,796, р=0,02), PAI-1 level - 75,95 ng/ml, (AUC 0,726, 95%CI 0,576-0,876, р=0,01), von Willebrand factor activity – 155,5% (AUC 0,724, 95%CI 0,561-0,887, р=0,01). Multivariate analysis revealed that concomitant diabetes mellitus, PRU ≥202, PAI-1 level ≥75.95 ng/ml, von Willebrand factor activity ≥155.15% are independent predictors of adverse cardiac events. Based on our findings we developed predictive models for risk stratifying of patients with CAD before PCI.
Conclusions: Present study reveals following independent predictors of adverse cardiac events in patients with SCAD after PCI: concomitant diabetes mellitus, the value of PRU (≥202), the level of plasminogen activator inhibitor-1 (≥75.95 ng/ml) and von Willebrand factor activity (≥155.15%).