P1756The protein APRIL predicts adverse outcomes in DAPT patients better than NT-proBNP and troponin

Abstract

Abstract Aim Dual antiplatelet therapy (DAPT) is a mainstay of post-ACS treatment. However, prediction of adverse events in these patients needs improving. We show here that the TNFα-related protein APRIL (which is produced in platelets and atherosclerotic plaque) is a superior predictor of MACE and new MI in DAPT recipients post-ACS. Methods We prospectively recruited 518 patients presenting with the primary complaint of acute chest pain to our hospital ED. Patients were adjudicated to have ACS by 2 independent cardiologists in accordance with ESC guidelines with hsTnI as biomarker. Plasma EDTA samples taken at presentation and 2 hours after were interrogated for APRIL measurements using a two site ELISA. Clinical data/variables, standard biochemistry analytes, hsTnT and NT-proBNP were also measured. Statistical assessments were made using SPSS v23 (IBM). Data for all biomarkers were treated as continuous variables and are presented as median (interquartile range, (IQR)). Statistical assessment of the comparative diagnostic abilities of APRIL, hsTnT, NT-proBNP and hsTnI were assessed using receiver operator curve (ROC) area under the curve (AUC) analysis. The comparative power of each biomarker (log values) to predict new MACE, MI, bleeding and mortality in 1) the whole group and in 2) DAPT recipients alone, within 2 yrs of index presentation was undertaken using a logistic regression base model (95% CI) that included all clinical variables and hsTnI and hsTnT, with APRIL and NT-proBNP each included in additional multivariate analyses. Results Of the 518 recruited patients (median age 63 (IQR: 54–73, 35% female), 152 were adjudicated to have ACS (29%, 115 MI, 37 UAP). Presentation APRIL levels were higher in those with a cardiac versus non-cardiac cause for presentation (3.0, (2.0–4.7) vs. 2.4, (1.6–3.8) ng/mL, P=0.001) and positively correlated with hsTnT and NT-proBNP (all P<0.001), but it did not add to the hsTnI (ROC = 0.96) or hsTnT (ROC =0.92) assisted diagnosis of ACS. In all 518 patients, in the multivariate regression model, APRIL was a significant independent predictor of mortality (n=54, P=0.032), new MI (n=43, P=0.006), new ADHF (n=24, P=0.016) and MACE (n=71, P=0.005) that was additive to NT-proBNP and troponin. In DAPT recipients alone (n=156), APRIL was the only biomarker to independently predict new MI (n=27, 95% CI: 1.125–3.982, P=0.020) and MACE (n=37, 95% CI: 1.058–3.389, P=0.031). None of the markers, only age, predicted bleeding episodes. Conclusion APRIL is an platelet/plaque derived marker that provides independent risk assessment in ACS patients. In DAPT recipients, the ability of APRIL to predict new MI and MACE is superior to that of cardiac troponins and NT-proBNP and could be used to identify high risk individuals. Acknowledgement/Funding Health Research Council of New Zealand; Heart Foundation of New Zealand