🧭 REBEL Rundown
🔑 Key Points
- 🏥Multicenter Trial: Stepped-wedged RCT performed across 9 emergency departments including 4 free-standing EDs
- 👥High Enrollment: Very large sample size in both the standard care and accelerated protocol groups
- ♥️No increase in safe discharges: An accelerated (0/1-hour) troponin protocol did not increase the proportion of patients who could be safely discharged from the emergency department.
- 🟰 Non-inferior to standard of care: The accelerated protocol was noninferior to standard care with regards to death or MI and coronary revascularization procedures at 30 days.
💼Case
A 52 year old woman with a history of hypertension presents to your emergency department (ED) with a complaint of chest pain intermittently for the past 1-2 days. The exam is unremarkable and chest pain is resolved in the emergency department. EKG shows some old nonspecific T-wave abnormalities, but no acute ST-segment changes. Her initial troponin is negative, and the rest of her labs are within normal limits. You’ve seen some literature supporting the safe discharge of similar patients after a negative one-hour repeat troponin. You wonder whether that would be a reasonable strategy for this patient.
📝 Introduction
Over 20 million patients are evaluated in the United States each year for suspected myocardial infarction (MI), at a cost of $5-10 billion annually. Less than 5% of these patients have an acute coronary syndrome. Most institutions utilize a 0/3-hour protocol for serial troponin measurement, although some observational studies and randomized studies outside the US have suggested that 0/1-hour protocol may be a safe and effective way to manage these patients [1,2,3]. This study was the first randomized controlled trial in the US comparing a 0/1-hour protocol to the standard 0/3-hour protocol, with regards to the proportion of patients that could be safely discharged and the comparative 30-day outcomes (death or MI).
🧾 Paper
Miller J, et al. Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I: A United States-Based Stepped-Wedge, Randomized Trial. Ann Emerg Med. 2024. PMID: 38888531
Previously Covered On REBEL
- High Sensitivity Troponin Testing
- High Sensitivity Cardiac Troponin T in a Multisite United States Cohort
- Single Troponin Testing in ED Patients With Suspected Acute Myocardial Infarction
- Accelerated Diagnostic Protocol for Chest Pain Not Useful in a US Population?
- The HEAR Score: Does Very Low-Risk Acute Chest Pain Not Require Troponin Testing?
- Retrospective Validation of High-Sensitivity Troponin with 5 Clinical Decision Instruments
⚙️ What They Did
📈 Results:
💥 Critical Results
- Primary outcome – the study did not meet its primary endpoint as the accelerated protocol was not superior to standard care in the proportion of patients who were safely discharged from the ED.
- The upper limit of absolute risk difference in safety outcomes (death/MI) was within the prespecified 0.5% noninferiority margin. This confirmed that the accelerated protocol was not inferior to standard care regarding 30-day death/MI in patients not admitted to the hospital. There was no significant difference between the groups in death/MI or revascularization procedures.
💪🏽 Strengths
- Randomized Controlled Trial: the first US randomized controlled trial to compare the safety and effectiveness of the 0/1-hour (accelerated) protocol compared to 0/3-hour (standard care) protocol with a high-sensitivity troponin I (hs-cTnI) assay. It confirms the findings of the RAPID-TnT trial (Chew et al, 2019) [4] and others, supporting the use of an accelerated protocol.
- Multiple Centers: 9 emergency departments (EDs), including four free-standing EDs, which have not been included in many clinical trials.
- Large, diverse sample size: enrolled 32,609 patients over the course of less than 9 months, far exceeding the RAPID-TnT trial in Australia. A majority of patients (>51%) did not present with either chest pain or shortness of breath, mirroring the broad use of troponin testing in the United States.
- Tables and Figures: clearly defining their standard and accelerated protocols, and the cluster allocation in the stepped-wedge study design.
- Comparison: compared their findings to the well-known RAPID-TnT trial, though that trial utilized Troponin-T (hs-cTnT), as opposed to Troponin-I (hs-cTnI) used in this trial.
- Demographics: The standard protocol had 22.6% Black patients, and the accelerated protocol had 33.2% Black patients enrolled. This population is often underrepresented in clinical trials, and this study provides further background on their health needs.
- Efficiency: This trial adds to the body of literature supporting the safety and efficacy of an accelerated 0/1-hour protocol for the disposition of patients evaluated for possible ACS, compared to the standard 0/3-hour protocol. This could have a positive impact on length of stay and ED efficiency.
⚠️ Limitations
- Pandemic: Study occurred during the COVID-19 Pandemic. This may have altered outcomes. However, while the patient cohort as a whole did not show a difference in the proportion of patients discharged from the ED safely, the sensitivity analysis in which COVID-19 patients were excluded showed an increased odds of safe ED discharge in the accelerated protocol, as compared to standard care (aOR=1.14, 95% CI 1.03-1.25)
- Co-morbidities: Chronic conditions such as diabetes, hypertension, heart failure, and chronic kidney disease may predispose patients to having elevated troponin levels. These may be in the intermediate range (5 to 18 ng/L) and would not allow for discharge at the 1-hour mark in the accelerated protocol. Furthermore, the authors note that some patients with intermediate troponins who might have been discharged after one troponin under standard care may require more troponin draws under the accelerated protocol.
- Site Variability: There was considerable variability in the primary endpoint depending on ED site. The authors state that a site-specific protocol may be needed to account for different practice patterns and patient populations.
- Data limitations: The study relied on a statewide health information exchange and national databases to track adverse events, which may have led to missing data for both groups. In addition, actual troponin levels in the intermediate (4-18 ng/L) range were not available for patients in the standard care arm, limiting comparisons with analogous patients in the accelerated protocol arm.
- Length of ED stay: The study did not report data on patients’ length of stay in the ED, which potentially would have been one of the advantages of the accelerated protocol.
🗣️ Discussion
Trial Impact and Context
This trial found that the number of safe discharges did not increase when using an accelerated protocol as compared to the standard of care.
However, those who had MI excluded by the 1-hour mark in the accelerated protocol (either one troponin <4 or two troponins <8), which was 54.7% of their cohort, had an increase in the proportion of safe ED discharge irrespective of their HEART score. This may be the strongest advantage of the protocol, insofar as the truly lowest risk patients may be safely discharged within one hour.
The accelerated protocol was also found to be non-inferior to the standard protocol regarding 30-day death/MI in those discharged from the ED. The rate of revascularization procedures within 30 days did not differ between the two groups.
This study confirms previous evidence showing the safety of an accelerated 0/1-hour protocol and identifies a group of patients with low troponin levels who could be discharged after one troponin drawn on arrival.
Adopting an accelerated protocol could have a positive impact on length of stay, cost, and patient satisfaction, with no negative impact on safety or outcomes for these patients. Unfortunately, the study provided no data on any of these outcomes, which would be important to consider in the potential adoption of this protocol.
However, it is important to consider the impact of patient comorbidities on troponin values and the large variability between the centers in the study. These and other factors limit the external validity of the study findings. As the study investigators note, “the influence of the accelerated protocol likely will depend on site-specific characteristics such as practice patterns and patient populations. …[T]his heterogeneity suggests a need for future work on site-specific performance of accelerated protocols.” We agree.
Clinical Implications:
- Patients with a troponin level of less than 4 at hour 0 can be considered for safe discharge irrespective of their HEART score. For those with an initial troponin level of 4, a repeat troponin <8 at hour 1 can then be considered for safe discharge, as compared to a 3-hour level required by standard protocol.
📘 Author's Conclusion
“A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.”
💬 Our Conclusion
- There may be a benefit to using the accelerated protocol if the troponin remains in the low risk range at hour 1, which can potentially lead to earlier safe discharge from the ED.
- While the accelerated protocol (0/1 hour) showed non-inferiority to the standard protocol (0/3 hour) regarding safe ED discharges, we would be hesitant to adopt the protocol, given that those who fell into the intermediate group (troponin of 5-18) may require additional testing and resource utilization.
🚨 Clinical Bottom Line
This is a large, well-done study that has the potential to change practice for patients evaluated for chest pain and shorten the time to disposition for these patients. It will require further external validation before we can recommend its wide adoption.
🔙Back to the Case:
The patient has an EKG showing no acute ischemic changes, initial troponin (hs-cTnI) of 4 ng/L, and a repeat troponin of 6 ng/L one hour later. Chest pain is resolved in the ED. You have a shared decision-making discussion with the patient and agree to discharge her with strict return precautions. You talk to her cardiologist, who agrees with the discharge and will follow her in the office for outpatient management. On follow-up several months later, the patient has had no further episodes of chest pain.
📚 References
- Anand A,, et al.
High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial. Circulation. 2021;
PMID: 33752439 - Chew DP, et al.
A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes: The Rapid Assessment of Possible Acute Coronary Syndrome in the Emergency Department With High-Sensitivity Troponin T Study (RAPID-TnT). Circulation. 2019;.
PMID: 31478763 - Nestelberger T, et al.
Predicting Major Adverse Events in Patients With Acute Myocardial Infarction. J Am Coll Cardiol. 2019.
PMID: 31416527 - Twerenbold R, et al.
Outcome of Applying the ESC 0/1-hour Algorithm in Patients With Suspected Myocardial Infarction. J Am Coll Cardiol. 2019
PMID: 31345421
Meet the Authors
Mihir Shah, DO
Steven Hochman, MD
🔎 Your Deep-Dive Starts Here
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