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Aims This study tested the hypothesis that combining stress-induced biomarkers (copeptin or glucose) with high-sensitivity cardiac troponin (hs-cTn) increases diagnostic accuracy for non-ST-elevation myocardial infarction (NSTEMI) in patients presenting to the emergency department. Methods and results The ability to rule-out NSTEMI for combinations of baseline hs-cTnT or hs-cTnI with copeptin or glucose was compared with the European Society of Cardiology (ESC) hs-cTnT/I-only rule-out algorithms in two independent (one Norwegian and one international multicentre) diagnostic studies. Among 959 patients (median age 64 years, 60.5% male) with suspected NSTEMI in the Norwegian cohort, 13% had NSTEMI. Adding copeptin or glucose to hs-cTnT/I as a continuous variable did not improve discrimination as quantified by the area under the curve {e.g. hs-cTnT/copeptin 0.91 [95% confidence interval (CI) 0.89–0.93] vs. hs-cTnT alone 0.91 (95% CI 0.89–0.93); hs-cTnI/copeptin 0.85 (95% CI 0.82–0.87) vs. hs-cTnI alone 0.93 (95% CI 0.91–0.95)}, nor did adding copeptin &amp;lt;9 mmol/L or glucose &amp;lt;5.6 mmol/L increase the sensitivity of the rule-out provided by hs-cTnT &amp;lt;5 ng/L or hs-cTnI &amp;lt;4 ng/L in patients presenting more than 3 h after chest pain onset (target population in the ESC-0 h-algorithm). The combination decreased rule-out efficacy significantly (both P &amp;lt; 0.01). These findings were confirmed among 1272 patients (median age 62 years, 69.3% male) with suspected NSTEMI in the international validation cohort, of which 20.7% had NSTEMI. A trend towards increased sensitivity for the hs-cTnT/I/copeptin combinations (97–100% vs. 91–97% for the ESC-0 h-rule-out cut-offs) was observed in the Norwegian cohort. Conclusion Adding copeptin or glucose to hs-cTnT/I did not increase diagnostic performance when compared with current ESC guideline hs-cTnT/I-only 0 h-algorithms.

Adding stress biomarkers to high-sensitivity cardiac troponin for rapid non-ST-elevation myocardial infarction rule-out protocols