Ruling Out MI Safe With 0/1-Hour High-Sensitivity Troponin: RAPID-TNT

PARIS, France—Use of a 0/1-hour protocol using high-sensitivity cardiac troponin T (hs-cTnT) in patients with chest pain presenting to the emergency department does not increase the risk of death or MI at 30 days when compared with standard testing, according to results from the RAPID-TNT trial presented today at European Society of Cardiology Congress (ESC) 2019.

Participants randomized to the 0/1-hour hs-cTnT protocol were sent home sooner from the emergency department and were less likely to be referred for functional cardiac testing. There was a higher rate of myocardial injury and infarction at 30 days associated with the 0/1-hour protocol among patients with low troponin levels (≤ 29 ng/L), a finding the researchers attribute to greater use of invasive management.

For lead investigator Derek Chew, MBBS (Flinders University, Adelaide, Australia), the RAPID-TNT study reinforces the safety of the 0/1-hour protocol, noting that just 0.3% of 1,187 patients discharged with “rule-out” MI died or had an MI within 30 days (negative predictive value 99.6%).

“This is now prospective, patient-level data with physicians not used to the 0/1-hour protocol, not trained in it, and implemented within clinical practice,” Chew told TCTMD. “It’s safe for use and can improve hospital efficiency. That’s reassuring for emergency department physicians. In Australia, there are 1 million people who present with chest pain every year. It’s an enormous problem. The resources devoted to looking after these patients are not being used for other sicker patients in the emergency department.” 

The randomized trial, which was presented during an ESC Hot Line session today, included 3,378 subjects with suspected ACS presenting to four emergency departments in Adelaide, Australia. It was designed as a noninferiority study of the 0/1-hour protocol using hs-cTnT (Elecsys; Roche Diagnostics) compared with a standard 0/3-hour protocol with troponin T results.

In Australia, there are 1 million people who present with chest pain every year. . . . The resources devoted to looking after these patients are not being used for other sicker patients in the emergency department. Derek Chew

As part of the trial, the researchers masked cTnT levels if lower than 29 ng/L for physicians randomized to the standard 0/3-hour hs-cTnT protocol. Although the fifth-generation high-sensitivity assay has an upper limit of normal of 14 ng/L, they wanted to align the lower clinical reporting limit with that of the previous-generation assay because physicians had no previous access to hs-TnT results lower than 29 ng/L.

“Our study is unusual in that we’re the first to be able to randomize patients within practice,” said Chew. “If you think about it, you need to keep the clinician blinded to treatment and treatment practices, not just the result but also the norms of how to respond to therapies. What we wanted to know was not whether the test performs well, but rather how the health system responds to the change in sensitivity of the test with the [0/1-hour] protocol.”

Less Use of Functional Testing

The primary endpoint of death or MI within 30 days occurred in 1.0% of patients randomized to either the standard or the 0/1-hour hs-cTnT protocol. There was no difference in the working diagnosis of patients between the two protocols, with Chew stating that instituting the 0/1-hour approach in routine practice doesn’t appear to improve the diagnosis of MI.

More patients treated with the 0/1-hour protocol were discharged from the emergency department (45.1% vs 32.3% with the standard protocol; P < 0.001), while median length of stay in the emergency department was also reduced by 1.0 hour for the 0/1-hour arm. Additionally, fewer patients were referred for a stress echocardiograms or functional testing in the 0/1-hour group. 

For patients with a negative hs-cTnT test result, physicians were much more comfortable with not needing further cardiac testing, said Chew. Overall, there was no increased use of invasive coronary angiography in the 0/1-hour arm compared with the standard protocol. In a subgroup analysis of patients with hs-cTnT levels ≤ 29 ng/L, however, the rate of PCI within 30 days was 2.0% among those screened with the 0/1-hour protocol and 0.9% for those treated with the standard 0/3-hour protocol (P 0.010).

Chew said that this reflects a need for physicians to “reset” clinical practice as they get used to a greater level of troponin sensitivity.   

“We’re aware that there is an increase in the risk of periprocedural myocardial infarction and injury with this study,” he said, referring to patients screened with the 0/1-hour protocol and referred for PCI. Any potential long-term benefits of such referrals will require further study, he noted. “We think strategies to mitigate the risk for these patients with newly recognized low troponin levels will require some modification in the way we investigate these patients, potentially with the increased use on noninvasive testing, such as CT angiography,” he added. 

Kurt Huber, MD (Sigmund Freud University Medical School, Vienna, Austria), noted there are several commercially available immunoassays even more sensitive than the one tested in RAPID-TNT and these have all been tested using the 0/1-hour rule-out protocol. For that reason, the present study is unique, he told TCTMD, since it shows that clinicians can use the high-sensitivity assays, which are available in most European centers, to quickly rule out MI.

Regarding the reduction in length of stay in the emergency department, Huber said that even the 1-hour difference between the approaches is clinically relevant, particularly given that most departments are crowded and staff stretched thin. Nonetheless, the 0/1-hour protocol still allows time for discussion.

“Even if we act on the 0/1-hour strategy, it’s 4-and-a-half hours before the patient is released,” he said. “We always have a discussion 1 or 2 hours after the [hs-cTnT result] about what to do. Can we send the patient immediately home? Or is it better to keep the patient in the hospital a little longer? There could be other reasons for an elevation in troponin.”