Prognostic Performance of Multiple Biomarkers in Patients With Non-ST Elevation Acute Coronary Syndrome: Analysis From MERLIN-TIMI 36

Study Questions:

What is the prognostic importance of novel biomarkers [C-terminal provasopressin (copeptin), midregional-pro-adrenomedullin (MR-proADM), and midregional-pro-atrial natriuretic peptide (MR-proANP)] in patients with non-ST-segment elevation (NSTE)-acute coronary syndrome (ACS)?


The authors measured copeptin, MR-proADM, and MR-proANP in 4,432 patients with NSTE-ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial and followed for 1 year. The primary endpoint was composite of cardiovascular death and heart failure.


Patients in the highest quartile of each biomarker were at an increased risk of cardiovascular death or heart failure (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 each of the individual endpoints of cardiovascular death, heart failure, and myocardial infarction (all p ≤ 0.001). After adjustment for other covariates, each biomarker was independently associated with the primary endpoint at 1 year (adjusted hazard ratios: copeptin 1.71, MR-proADM 1.96, MR-proANP 2.20; all p ≤ 0.001). In all of the studies, biomarkers improved prognostic discrimination and patient re-classification for the primary endpoint at 1 year (all categorical net reclassification improvement [NRI] >10%, p < 0.001).


The authors concluded that copeptin, MR-proADM, and MR-proANP are complementary prognostic markers for death and heart failure in patients with NSTE-ACS.


Copeptin, MR-proADM, and MR-proANP are markers of hemodynamic stress, and as expected, are associated with risk of recurrent chronic heart failure. The clinical utility of these biomarkers remains uncertain at present. The risk adjustment in this study did not take into account hemodynamic variables (heart rate, blood pressure, jugular venous pressure, Killip class, etc.) or measures of left ventricular function, and it is unclear if these measures would improve risk stratification beyond that associated with risk models that take these measures into account. Further studies are needed to establish the clinical role of these markers in decision making before they can be incorporated into clinical practice.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, ACS and Cardiac Biomarkers, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Biological Markers, Ventricular Function, Left, Heart Failure, Atrial Natriuretic Factor, Adrenomedullin, Risk Adjustment

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