We have been searching for a tool to identify myocardial infarction patients who are truly safe for discharge ever since Pope, et al., found that we were discharging two percent of patients with MIs from the emergency department. (NewEngl J Med 2000;342:1163; http://bit.ly/2rwpNUJ.) Many have anointed the high-sensitivity troponin assay (hs-cTnI) for this role. The added sensitivity would identify a subset of ACS patients who would otherwise remain occult during their ED stay—in theory.
Such a sensitivity could come with a loss of specificity, a heavy price when the incidence of disease is low. Despite the theoretical advantages of hs-cTnI, evidence supporting its use is inconsistent at best. Now, with the recent publication of a cluster-randomized controlled trial by Shah, et al., we have evidence demonstrating the clinical consequences of high-sensitivity assays on patient care. (Lancet 2018;392:919; http://bit.ly/2Erob7e.)
The authors performed a stepped-wedge, cluster-randomized controlled trial in 10 EDs. Patients presenting with signs and symptoms concerning for ACS underwent an evaluation during which a standard troponin and a high-sensitivity assay were drawn. The study was divided into the validation phase, in which the hs-cTnI was drawn with results not divulged to the treating clinicians, and the implementation phase, during which the hs-cTnI was incorporated into clinical decision-making. All sites underwent at least six months of a validation phase after which they were randomly assigned to an immediate implementation phase or a delayed implementation phase following an additional six months of the validation.
The authors enrolled 48,282 patients over three years, and 18,978 (39%) were enrolled during the validation phase and 29,304 (61%) during the implementation phase. A total of 10,360 (21%) patients had an hs-cTnI value that was above the 99th percentile. The majority of these patients (83%) also had an elevated contemporary troponin assay, with only 17 percent reclassified using the hs-Tn. The authors found no difference in their primary outcome—the rate of subsequent myocardial infarction (type 1 or type 4b) or cardiovascular death within one year following the initial presentation to hospital (6% vs 5% in the validation and implementation phases, respectively).
Patients who were reclassified using the hs-cTnI were more likely than those who had congruent negative troponin assays to suffer a subsequent myocardial infarction or death. Despite this increased risk of adverse events, clinician awareness of the elevations in hs-cTnI did not improve patient-oriented outcomes. Hs-cTnI was a predictor of a sicker subset of the population, but it did not identify a group of patients who benefited from a more aggressive treatment strategy.
Not Much Has Changed
Despite our hopes, it would appear that the introduction of hs-cTnI added very little to the workup of patients presenting with symptoms concerning for ACS. In fact, the utilization likely led to a significant degree of overdiagnosis, downstream testing, and overtreatment. The use of hs-cTnI increased the number of patients diagnosed with myocardial injury by 17 percent, but only a third of these patients had a diagnosis of type 1 myocardial infarction.
Patients reclassified by the high-sensitivity assay were more likely to undergo coronary angiography in the implementation phase compared with the validation phase, (11% in the implementation phase v. 4% in the validation phase), and more frequently received prescriptions for antiplatelet agents, dual-antiplatelet agents, statins, and beta-blockers, all without improving important patient outcomes. The full extent of the overdiagnosis is likely understated in this dataset because the authors utilized the hs-cTnI as their diagnostic gold standard when ascertaining which patients experienced an MI during the one-year follow-up.
These results should not come as a surprise. They are simply the consequence of using a more sensitive assay. How many patients will be falsely diagnosed with ACS and suffer the downstream consequences of such a diagnostic burden? Despite many years of progression in the understanding of ACS, a host of novel biomarkers, and a brand new high-sensitivity troponin assay, not much has changed since the publication of the infamous Pope trial. We are still missing one to two percent of MIs following a negative ED workup.
It would seem that the introduction of the hs-cTnI has not changed that number. This study is far from perfect. The one-year outcome that was selected as the primary endpoint is less than ideal for evaluating the downstream consequences of a diagnostic strategy from the ED, and small differences in outcomes could have been missed because of the study design. Despite these shortcomings, the results from Shah, et al., should give us pause before we anoint hs-cTnI as the diagnostic savior in evaluating chest pain patients.
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