High-sensitivity cardiac troponin on presentation to rule out myocardial infarction: a stepped-wedge cluster randomised controlled trial

Objectives: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the efficacy and safety of this approach is uncertain. We investigated whether an early-rule out pathway is safe and effective for the management of patients with suspected acute coronary syndrome. Design: A stepped-wedge cluster randomised controlled trial. Setting: Seven acute care hospitals in Scotland. Participants: 31,492 consecutive patients with suspected acute coronary syndrome between December 2014 to December 2016. Intervention: Sites were randomised to implement an early rule-out pathway where myocardial infarction was ruled out if high-sensitivity cardiac troponin I concentrations were <5 ng/L at presentation. During a prior validation phase, myocardial infarction was ruled out where troponin concentrations were <99th centile at 6-12 hours after symptom onset. Main outcome measures: The co-primary outcome was length of stay (efficacy), and myocardial infarction or cardiac death after discharge at 30 days (safety). Patients were followed for 1 year to evaluate the safety outcome and other secondary outcomes. Results: We enrolled 31,492 patients (59±17 years, 45% women) with troponin concentrations <99th centile at presentation. The length of stay was reduced from 10.1±4.1 to 6.8±3.9 hours (adjusted geometric mean ratio 0.78, 95% confidence interval [CI] 0.73 to 0.83, P<0.001) following implementation, and the proportion of patients discharged increased from 50% to 71% (adjusted odds ratio [aOR] 1.59, 95% CI 1.45 to 1.75). Non-inferiority was not demonstrated for the 30-day safety outcome (upper limit of one-sided 95% CI for adjusted risk difference 0.70%, non-inferiority margin 0.50%, P=0.068), but the observed differences favoured the early rule-out pathway (0.4% [57/14,700] versus 0.3% [56/16,792]). At 1 year, the safety outcome occurred in 2.7% (396/14,700) and 1.8% (307/16,792) of patients before and after implementation (aOR 1.02, 95% CI 0.74 to 1.40, P=0.894), and there were no differences in hospital reattendance or all-cause mortality. Conclusions: Implementation of an early rule-out pathway for myocardial infarction reduced length of stay and hospital admission. Whilst non-inferiority for the safety outcome was not demonstrated at 30 days, there was no increase in cardiac events at 1 year. Adoption of this pathway will have major benefits for patients and healthcare providers. Trial registration: ClinicalTrials.gov number, NCT03005158