Copeptin with high-sensitivity cardiac troponin to rule out non-ST-elevation myocardial infarction early on: A systematic review and meta-analysis

High-sensitivity cardiac troponin (hs-cTn) with copeptin in rapidly ruling out non-ST-elevation myocardial infarction (NSTEMI) remains controversial. We aimed to evaluate the diagnostic accuracy of this combination compared to hs-cTn alone. A literature search of electronic databases was performed from inception to 26 March 2022. Primary studies that evaluated the diagnostic accuracy of hs-cTn with and without copeptin in patients with NSTEMI were eligible. The reference standard consisted of all available medical results, including a significant rise or fall of cTn with at least one value above the 99th percentile of the reference population. The QUality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the quality of the included studies. Thirteen studies involving 8,966 patients, 1,405 of whom were diagnosed with NSTEMI (prevalence, 15.67 %), were included. Combining copeptin with hs-cTn (99th percentile of the healthy population as the threshold) at admission improved the sensitivity from 0.89 to 0.96 (95 % confidence interval [CI] 0.84-0.93 vs 0.93-0.98); the specificity reduced from 0.79 to 0.56 (95 % CI 0.71-0.86 vs 0.51-0.60). In five studies with 6,073 participants (900 NSTEMI), the hs-cTn alone (with 'very low' or limit of detection [LoD] threshold) had higher diagnostic sensitivity than the dual-marker strategy (0.98 vs 0.96). Combining copeptin with hs-cTn (99th percentile of the population as the threshold) at admission improved sensitivity in NSTEMI identification at the expense of specificity. However, with the LoD threshold for hs-cTn, copeptin had no additional value, deterring the widespread use of copeptin if the hs-cTn assay is clinically available.