High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial

Abstract

Background: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an early-rule out pathway is safe and effective for patients with suspected acute coronary syndrome. Methods: We performed a stepped-wedge cluster randomized controlled trial in the Emergency Departments of seven acute care hospitals in Scotland. Consecutive patients presenting with suspected acute coronary syndrome between December 2014 and December 2016 were included. Sites were randomized to implement an early rule-out pathway where myocardial infarction was excluded 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. 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 safety and other secondary outcomes. Results: We enrolled 31,492 patients (59±17 years, 45% women) with troponin concentrations <99th centile at presentation. 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 would have major benefits for patients and healthcare providers. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03005158

Troponin-Guided Coronary Computed Tomographic Angiography After Exclusion of Myocardial Infarction

“…The discovery that low troponin concentrations identify patients who are at low risk of cardiac events has led to the development of accelerated care pathways for patients with suspected acute coronary syndrome ( 6 , 20 , 21 , 22 ). Recent evidence from randomized controlled trials has shown that implementation of this approach is safe and effective at substantially reducing length of hospital stay and the proportion of patients who require hospital admission ( 23 ). In contrast, among patients in whom myocardial infarction has been ruled out, an intermediate troponin concentration within the normal reference range is associated with a 5-10× higher medium- and long-term risk of adverse cardiac events compared with those with a low (<5 ng/L) troponin concentration ( 4 , 5 ).…”

Diagnostic Performance of Serial High-Sensitivity Cardiac Troponin Measurements in the Emergency Setting

“…In Cohort-2, there was a clinical recommendation to collect samples 3 h apart as per the Canadian Institutes of Health Research funded grant and study protocol [24]. As the diagnostic parameters have been published for the ESC 0/1 h algorithm cutoffs (sensitivity/NPV/specificity/PPV of 97.8%/99.4%/91.3%/50%) in Cohort-2 [24], the 0/2 h algorithm cutoffs were assessed (as the ESC recommends to use the 0/2 h algorithm as an alternative to the 0/1 h algorithm) [3], as well as the High-STEACS pathway [14] and COMPASS-MI algorithm [5] in both cohorts (see Table 1 for details of the algorithms). For COMPASS-MI, physicians can select different cutoffs as detailed in the original publication and using the web-based calculator (https://compass-mi.com/ accessed on 26 April 2021) [5].…”

“…Others have proposed predictive values be used [10], with the following diagnostic estimates being evaluated in studies: sensitivity ≥ 99% or negative predictive value (NPV) ≥ 99.5% for rule-out and specificity ≥ 90% or positive predictive value (PPV) ≥ 75% for rule-in [11][12][13]. Many algorithms have been developed and implemented based mainly on predictive values, and despite the number of published algorithms increasing, there are few headto-head comparison studies performed in the same cohorts with even fewer algorithms validated in external populations to assess generalizability [3,10,14,15].…”

“…In the present study, we evaluated the three main published hsTnI algorithms that use serial measurements [3,5,14] in two different ED cohorts for 30-day MI or death (a common outcome reported by studies using these algorithms) [3,5,14]. In both cohorts, physicians were blinded to the hsTnI results with the cardiac troponin test being reported clinically belonging to a non-hsTn test version (note, standard, conventional or contemporary are terms that are also used to describe non-hsTn tests).…”

Implementing an early rule-out pathway for acute myocardial infarction in clinical practice

“…4 These guideline recommendations are supported by recent randomised trials that have provided new insights into the safety and effectiveness of these pathways in clinical practice. [5][6][7] Multiple pathways have been proposed that vary according to the thresholds used for decision-making and timing of sampling. Implementing a validated pathway could save healthcare resources and improve the safe delivery of patient care.…”