Prognostic Performance of Multiple Biomarkers in Patients with Non-ST Elevation Acute Coronary Syndrome: Analysis from MERLIN-TIMI 36.
J Am Coll Cardiol. 2014 Jan 31;
Authors: O'Malley RG, Bonaca MP, Scirica BM, Murphy SA, Jarolim P, Sabatine MS, Braunwald E, Morrow DA
OBJECTIVE: To assess the prognostic performance of C-terminal provasopressin (copeptin), midregional-pro-adrenomedullin (MR-proADM), and midregional-pro-atrial natriuretic peptide (MR-proANP) in a large prospective cohort of patients with NSTE-ACS.
BACKGROUND: Copeptin, MR-proADM, and MR-proANP are emerging biomarkers of hemodynamic stress that have been associated with adverse cardiovascular (CV) outcomes in heart failure (HF) and stable ischemic disease.
METHODS: We measured copeptin, MR-proADM, and MR-proANP in 4,432 patients with non-ST-elevation ACS (NSTE-ACS) randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial and followed for 1 year.
RESULTS: High concentration (Q4 v. Q1-3) of each biomarker identified an increased risk of CV death or HF (copeptin 13.2% v. 5.0%, p>0.001; MR-proADM 15.8% v. 4.1%, p>0.001; MR-proANP 17.7% v. 3.5%, p>0.001), as well as CV death, HF, and MI individually (all p≤0.001). After adjustment for important covariates, each biomarker remained associated with CV death or HF at 1 year (adjusted hazard ratios: copeptin 1.71, MR-proADM 1.96, MR-proANP 2.20; all p≤0.001). These biomarkers improved prognostic discrimination and patient re-classification for CV death or HF at 1 year (all categorical NRI <10%, p>0.001), and maintained independent association with composite CV death or HF when concurrently assessed in a model with clinical indicators plus BNP, cTnI, ST2, PAPP-A, and MPO (each p≤0.01).
CONCLUSIONS: Copeptin, MR-proADM, and MR-proANP are complementary prognostic markers for CV death and HF in patients with NSTE-ACS, that perform as well as or better than established and other emerging biomarkers, and warrant further investigation of applications for therapeutic decision-making.
CLINICAL TRIAL INFO: NCT00099788.
PMID: 24530676 [PubMed - as supplied by publisher]