Prognostic Performance of Multiple Biomarkers in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome : Analysis From the MERLIN–TIMI 36 Trial (Metabolic Efficiency With Ranolazine for Less Ischemia in Non−ST-Elevation Acute Coronary Syndromes–T

ObjectivesThe aim of this study was 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 non–ST-segment elevation acute coronary syndrome (NSTE-ACS).BackgroundCopeptin, 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.MethodsWe measured copeptin, MR-proADM, and MR-proANP concentrations in 4,432 patients with NSTE-ACS who were randomized to treatment with ranolazine or placebo in the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non−ST-Elevation Acute Coronary Syndromes–Thrombolysis In Myocardial Infarction 36) trial and followed up for 1 year.ResultsA high concentration (quartile 4 vs. quartiles 1 to 3) of each biomarker identified an increased risk of CV death or HF (copeptin: 13.2% vs. 5.0%, p > 0.001; MR-proADM: 15.8% vs. 4.1%, p > 0.001; MR-proANP: 17.7% vs. 3.5%, p > 0.001) as well as CV death, HF, and myocardial infarction individually (all p ≤ 0.001). After adjustment for important covariates, each biomarker remained associated with CV death or HF at 1 year (adjusted hazard ratio: copeptin, 1.71; MR-proADM, 1.96; MR-proANP, 2.20; all p ≤ 0.001). These biomarkers improved prognostic discrimination and patient reclassification for CV death or HF at 1 year (all categorical net reclassification improvement: <10%; p > 0.001) and maintained an independent association with composite CV death or HF when concurrently assessed in a model with clinical indicators plus B-type natriuretic peptide, cardiac troponin I, ST2, pregnancy-associated plasma protein A, and myeloperoxidase (each p ≤ 0.01).ConclusionsCopeptin, 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 application for therapeutic decision making. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788)