Cardiac Troponin Testing

As previously described, cardiac troponin testing was performed at presentation and repeated 6 or 12 hours after the onset of symptoms at the discretion of the attending clinician in accordance with national and international guidelines in use during enrollment.^19,23,24 In all patients during both phases of the trial, cardiac troponin was measured using the ARCHITECT_STAT high-sensitive troponin I assay (Abbott Laboratories, Abbott Park, IL). This assay has a limit of detection of between 1.2 ng/L and 1.9 ng/L,²⁵ and for consistency with prior studies we defined this as any concentration <2 ng/L.²⁶ For the purpose of this analysis, all patients with an undetectable troponin concentration were assigned a value of 1.0 ng/L. The inter-assay coefficient of variation is less than 10% at 4.7 ng/L and the sex-specific 99th centile diagnostic thresholds are 16 ng/L for women and 34 ng/L for men.²⁷ High-sensitivity cardiac troponin I concentrations were only disclosed to clinicians during the implementation phase of the trial, but given risk stratification thresholds were not used to guide clinical decisions we pooled data from both phases of the trial for the purpose of this analysis.

In the substudy, samples were also analyzed using the Siemens Atellica high-sensitivity cardiac troponin I assay and Roche Elycsys high-sensitivity cardiac troponin T assays.^5,22 For these assays the limit of detection is 1.6 ng/L and 5 ng/L respectively, and the limit of blank for the cardiac troponin T assay is 3 ng/L. For all 3 assays, we evaluated performance of the risk stratification threshold of 5 ng/L, the lower threshold of <2 ng/L for cardiac troponin I, and <3 ng/L for cardiac troponin T, as these thresholds are equivalent to the limit of detection and limit of blank, respectively.