HiSTORIC Trial Supports Single-Test Rule-Out of MI Using High-Sensitivity Troponin
“The cost savings of this single test when used effectively could be absolutely enormous,” a researcher says.
PARIS, France (UPDATED)—Using a single measurement of cardiac troponin I with a high-sensitivity assay to triage patients presenting with suspected ACS promises to clear out emergency departments (EDs) faster without increasing adverse cardiac events, the cluster-randomized HiSTORIC trial demonstrates.
Implementing the High-STEACS early rule-out pathway across seven centers in Scotland reduced the time patients spent in the ED by 3.3 hours (from 10.1 to 6.8 hours) and increased the proportion of patients sent home without being admitted (74% vs 53%; P < 0.0001 for both) compared with standard rule-out using the 99th percentile as a cutoff, according to Nicholas Mills, MBChB, PhD (University of Edinburgh, Scotland).
The trial was not able to establish that the speedier pathway was noninferior to standard protocols in terms of MI/cardiac death occurring between discharge and 30 days, but the rate was numerically lower with the High-STEACS approach (0.3% vs 0.4%). That advantage was maintained at 1 year (1.8% vs 2.7%), Mills reported here at the European Society of Cardiology (ESC) Congress 2019.
“Adoption of this approach will have major benefits for both patients and healthcare providers,” he said at a press conference.
Practice in Scotland has already changed to incorporate early rule-out with a single test, and that other countries are moving in that direction as well, Mills said. “If we can make an evaluation that is safe with a single test on presentation to hospital [and] avoid a hospital admission and all the downstream investigations that certainly in many healthcare systems are standard practice, then the cost savings of this single test when used effectively could be absolutely enormous.”
‘Simple, Pragmatic, Easy to Use’
Other studies have explored use of a single measurement using a high-sensitivity troponin assay to rule out MI, including one recently conducted among US centers. But HiSTORIC is the first randomized controlled trial to evaluate the efficacy and safety of implementing that approach.
The study was a stepped-wedge, cluster-randomized trial that involved three phases:
- During the 6- to 9-month validation phase, all seven participating centers used a standard
- During the 6-month randomization phase, centers transitioned to the High-STEACS early rule-out pathway in three steps.
- During the 6- to 9-month implementation phase, all centers used the expedited pathway.
Troponin testing was performed using the ARCHITECTSTAT high-sensitivity cardiac troponin I assay (Abbott Diagnostics).
Mills described the High-STEACS pathway as “simple, pragmatic, easy to use.” In short, patients with a troponin value at presentation below 5 ng/L (which has a negative predictive value of 99.5% for ruling out MI) can be sent home, with the exception of early presenters, who are retested after 3 hours. Patients with a value above the sex-specific 99th percentile at presentation are admitted for further evaluation. Intermediate patients with values between 5 ng/L and the 99th percentile are retested after 3 hours, and at that point, patients with little change in troponin can be sent home and those with a change of at least 3 ng/L are admitted for further evaluation.
When this approach is used ideally, 75% of patients will be managed as outpatients and the rest as inpatients, Mills said.
Overall, the study included 14,700 patients handled with standard rule-out protocols and 16,792 managed with the rapid rule-out pathway, showing that the High-STEACS approach shortened time in the ED and sent more patients home directly from the ED without increasing MI/cardiac death through 1 year.
“We were able to conclude that discharging more patients from hospital was not associated with adverse outcome,” Mills said. He added that it was not surprising that implementation of the rapid rule-out protocol was safe. “I think there is an argument that it might be superior to using 99th centile, not just in terms of efficacy, because it helps clinicians to focus on the highest-risk patients,” Mills said. “So there are lots of practical reasons why I think this should be the way we triage patients with acute chest pain.”
Commenting for TCTMD, American College of Cardiology spokesperson B. Hadley Wilson, MD (Sanger Heart & Vascular Institute, Charlotte, NC), said the impact of implementing such a protocol based on a single troponin test was dramatic, noting that in the United States, serial testing at 3, 6, or even 12 hours after presentation is still performed.
If use of a single test at presentation is adopted more broadly, “it’s going to really unburden a lot of emergency departments and hospitals and hopefully reduce a lot of care and testing that maybe had been done before,” Wilson said. “So I think it’s dramatic. I think it’s going to be important internationally and I think it will also impact American practice and guidelines.”
Although high-sensitivity troponin testing is slowly gaining traction in the United States, most centers that are using it are still doing some kind of serial testing. It’ll likely take further trials conducted in US centers to convince American physicians and guideline writers to move toward single-test rule-out, Wilson said.
HiSTORIC is not going to change practice tomorrow, particularly in the US, he said, but “it’s going to send a strong enough message that US centers are going to want to confirm that and then look at moving along to . . . testing with a single assay, and that’s so huge to us in terms of concerns about our healthcare costs as well as to patients, who don’t want to be hanging around emergency departments any longer than they have to.”
Serving as discussant following Mills’ presentation, Hugo Katus, MD, PhD (Heidelberg University Hospital, Germany), called HiSTORIC an “urgently needed and well-conducted trial.”
The results “are consistent and reassuring,” Katus said. “That means early rule-out with high-sensitivity troponin is effective and it is safe. There was no adverse signal.”
He identified a few issues to consider, however. He asked whether the trial really evaluated an early rule-out protocol when the delay between presentation and first blood sampling was 66 minutes, longer than the 60 minutes recommended in ESC guidelines. In addition, the standard protocol called for repeat testing at 6 to 12 hours after symptom onset. “This will increase inappropriately length of stay in hospital as compared to ESC guidelines,” which recommend using a rapid rule-out protocol with testing at presentation and at 3 hours when high-sensitivity assays are available.
Katus also highlighted the all-cause death rate in the trial, which was over 5% in both groups at 1 year, and the reattendance rate of about 39%. “So are we, by discharging the patients as rule-out, cardiovascular rule-out, [ignoring] other life-threatening conditions?”
Notwithstanding those considerations, Katus said the trial demonstrates that accelerated rule-out using a high-sensitivity troponin I assay is efficient and safe, noting that not all troponin I assays have been validated.
“Be also aware that HiSTORIC does not prohibit careful clinical workup in these patients,” he said.
Mills N. High-sensitivity cardiac troponin at presentation to rule out myocardial infarction (HiSTORIC): a stepped-wedge cluster-randomised controlled trial. Presented at: ESC 2019. September 1, 2019. Paris, France.
- The trial was funded by the British Heart Foundation.
- Mills reports having research contracts with Abbott Diagnostics and Siemens Healthineers.
- Wilson reports no relevant conflicts of interest.
- Katus reports holding a patent on cardiac troponin T in the United States and consulting for AstraZeneca, Bayer Vital, Boehringer Ingelheim, and Novo Nordisk.