Using the European Society of Cardiology (ESC) 0/1-hour high-sensitivity troponin (hs-cTn) accelerated diagnostic pathway (ADP) did not result in significantly more patients being discharged within four hours of presentation vs. the 0/3-hour ADP, and when looking at safety of discharge, the ESC 0/1-hour ADP was noninferior to the 0/3-hour ADP, according to the MACROS-2 randomized, noninferiority trial published May 20 in JACC.

James Hatherley, MBChB, et al., included 3,543 patients (median age 60 years, 53% men) with suspected acute coronary syndrome (ACS) from two major emergency departments (EDs) in England, comparing the efficiency and safety of the ESC 0/1-hour and 0/3-hour pathways. Efficiency was measured by the proportion of patients discharged within four hours, and the safety endpoint was major adverse cardiac events (MACE) within 30 days among those determined to not have ACS and were discharged. The noninferiority margin was set at 3%.

Comparing the proportion of patients discharged within four hours, rates were relatively low with no significant difference between the two groups (228% vs. 19%, p=0.07). The central laboratory turnaround time for hs-cTn was 81 minutes (IQR, 69-101 minutes), contributing along with ED overcrowding and system constraints to delays in discharge.

The 0/1-hour pathway was also found to be noninferior for safety of discharge vs. the 0/3-hour pathway. Absolute difference in sensitivity was +4.2% (one-sided 97.5% CI, –2.5), favoring the 0/1-hour pathway.

"This trial highlights the challenges of implementing ADPs into clinical practice and that real-world clinical performance may be inferior to that implied by observational, algorithm-level studies," write the authors. "In addition, an ever-decreasing sampling interval may result in a rule of diminishing returns (in terms of early discharge)."

"The results of MACROS-2 remind us that even when clinical pathways have been validated in rigorous trials, these pathways may not perform as well in some real-world practice setting," adds Jason H. Wasfy, MD, MPhil, FACC, in an Editor's Note. "Laboratory turnaround times, clinical decision-making and limited resources in clinical practice can challenge effective practical implementation of even the best-validated clinical pathways."

In an accompanying editorial comment, Luca Crisanti, MD, et al., point to other new developments, such as the novel cardiac myosin-binding protein C or the combination of hs-cTnI with hs-cTnT, which may improve diagnostic discrimination. "Ultimately, these efforts will enable physicians to even more rapidly and more effectively rule-out and rule-in [acute myocardial infarction] in the ED and thereby accelerate patient flow," they write.