A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes

Abstract

Background: High-sensitivity troponin assays promise earlier discrimination of myocardial infarction. Yet, the benefits and harms of this improved discriminatory performance when incorporated within rapid testing protocols, with respect to subsequent testing and clinical events, has not been evaluated in an in-practice patient-level randomized study. This multicenter study evaluated the noninferiority of a 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol in comparison with a 0/3-hour masked hs-cTnT protocol in patients with suspected acute coronary syndrome presenting to the emergency department (ED). Methods: Patients were randomly assigned to either a 0/1-hour hs-cTnT protocol (reported to the limit of detection [<5 ng/L]) or masked hs-cTnT reported to ≤29 ng/L evaluated at 0/3-hours (standard arm). The 30-day primary end point was all-cause death and myocardial infarction. Noninferiority was defined as an absolute margin of 0.5% determined by Poisson regression. Results: In total, 3378 participants with an emergency presentation were randomly assigned between August 2015 and April 2019. Ninety participants were deemed ineligible or withdrew consent. The remaining participants received care guided either by the 0/1-hour hs-cTnT protocol (n=1646) or the 0/3-hour standard masked hs-cTnT protocol (n=1642) and were followed for 30 days. Median age was 59 (49–70) years, and 47% were female. Participants in the 0/1-hour arm were more likely to be discharged from the ED (0/1-hour arm: 45.1% versus standard arm: 32.3%, P <0.001) and median ED length of stay was shorter (0/1-hour arm: 4.6 [interquartile range, 3.4–6.4] hours versus standard arm: 5.6 (interquartile range, 4.0–7.1) hours, P <0.001). Those randomly assigned to the 0/1-hour protocol were less likely to undergo functional cardiac testing (0/1-hour arm: 7.5% versus standard arm: 11.0%, P <0.001). The 0/1-hour hs-cTnT protocol was not inferior to standard care (0/1-hour arm: 18/1646 [1.1%] versus 16/1642 [1.0%]; incidence rate ratio, 1.06 [ 0.53–2.11], noninferiority P value=0.001, superiority P value=0.744), although an increase in myocardial injury was observed. Among patients discharged from ED, the 0/1-hour protocol had a negative predictive value of 99.6% (95% CI, 99.0–99.9%) for 30-day death or myocardial infarction. Conclusions: This in-practice evaluation of a 0/1-hour hs-cTnT protocol embedded in ED care enabled more rapid discharge of patients with suspected acute coronary syndrome. Improving short-term outcomes among patients with newly recognized troponin T elevation will require an evolution in management strategies for these patients. Clinical Trial Registration: URL: https://www.anzctr.org.au . Unique identifier: ACTRN12615001379505.

Limit of detection of troponin discharge strategy versus usual care: randomised controlled trial

“…One randomised controlled trial of over 3000 participants evaluating the ESCrecommended Roche hs-cTnT assay of 0 and 1 hour, rule-out strategy demonstrated improved clinical effectiveness in terms of rapid discharge from the ED, but compared this strategy to a control group where contemporary cut-offs were used, which may have inflated the results. 23 Our trial has several strengths that distinguish it from prior studies and extend the generalisability of the findings. First, we tested a strategy that does not rely on a risk score.…”

“…Third, previous trials have tested hs-cTn assays provided by a single manufacturer. 23 This approach can have significant limitations in terms of generalisability because hospitals may have limited opportunity to change assays. By applying the LoDED strategy across the three different troponin assays in which the undetectable cut-off has been evaluated in observational studies, we have enhanced the generalisability of our findings.…”

High-sensitivity troponin in chronic kidney disease: Considerations in myocardial infarction and beyond

“…These protocols shorten the time of repeat troponin testing from 3-6 hours (Thygesen et al, 2012) to 0-2 hours (Lindahl et al, 2016;McRae et al, 2017). In 2019, a 1-hour protocol was validated in the only randomised trial to date (Chew et al, 2019), which demonstrated non-inferiority to standard-of-care for safety outcomes with reduced emergency department length of stay and subsequent hospital admission (Thygesen et al, 2010). However, these assays come with new challenges including increased identification of troponin elevations above the conventional reference threshold in patients without objective evidence of myocardial ischaemia (Chew et al, 2019;Shah et al, 2018).…”

High-sensitivity cardiac troponin and the early rule out of myocardial infarction: time for action

“…Notably, the ESC 0/1 hour algorithm has already been evaluated in a prospective randomised controlled trial. 6 Chew et al randomly assigned 3378 patients with suspected acute coronary syndrome to either the ESC 0/1 hour hs-cTnT pathway, or a standard care arm using hs-cTnT at the 99th centile. They demonstrated an increased rate of discharge from the emergency department with the 0/1 hour algorithm (45.1% vs 32.3%, p<0.001) and a reduced length of stay (4.6, IQR (3.4-6.4) hours vs 5.6 (4.0-7.1) hours, p<0.001).…”