Can composite risk scores improve upon single sample rule-out performance in suspected acute coronary syndrome? A preplanned analysis of the MACROS 2 randomised controlled trial

Introduction Assessment of suspected acute coronary syndrome involves a triad of high sensitive troponins, electrocardiogram and clinical assessment. However, it is a matter of controversy whether early rule-out and discharge is better affected by formal risk score evaluation, which seeks to incorporate all 3 of these parameters. We investigated the optimum means of rule out using a single presentation hs-cTn in a preplanned analysis of the MACROS 2 randomised controlled trial. Methods Early rule-out by risk scores (using hs-cTn) was compared to the guideline recommended SSRO threshold for the 3 hs-cTns [including hs-cTnT Roche elecsys, hs-cTnI (Siemens Attellica) and hs-cTnI (Quidel triage true, point of care)]. In total, 3543 patients were enrolled in the MACROS 2 randomised controlled trial of the ESC 0/1 versus 0/3 hour accelerated pathway. Clinical details and symptom evaluation were undertaken directly by patient interview at the time of presentation with acute chest pain. Event adjudication for myocardial infarction (MI), by paired consultant cardiologists, was undertaken using Abbott Alinity hs-cTnI following the 4th universal definition. The following risk scores (RS) were determined (by code) with relevant details, including specific symptoms automatically extracted from the research database: HEART, recalibrated HEART (recalibrated to limit of detection[LOD]), TIMI and T-MACS. National follow up was achieved by means of a Unique ID linked database. Clinical effectiveness was denoted by percentage of cohort that could be rule-out and safety by 30 day MACE (major adverse cardiac event rate- adjudicated type 1 myocardial infarction, unplanned coronary revascularisation and cardiovascular death) Results From December 2021 to July 2024, 3543 individual patients with suspected ACS were prospectively recruited from two major emergency departments (EDs) in Northern England and 100% follow-up was achieved from 13 hospitals nationally. The mean age was 59 years, 53% were male, 6.9% had an index type 1 myocardial infarction and 7.8% had a MACE within 30 days. The results are demonstrated in the table. For hs-cTnT (Roche elecsys) only recalibrated HEART≤3, T-MACS <2% and hs-cTnT <5 ng/l alone had > 98% sensitivity for 30-day MACE rule-out. However, T-MACS was most efficient in terms of discharge followed by recalibrated HEART≤3. For hs-cTnI (both Quidel TT POC and Siemens attellica) however all risk scores ruled out considerably less patients than using SSRO alone. Conclusion SSRO with low level hs-cTn alone was consistently safe across all troponins, hs-cTn T or I. T-MACS and recalibrated HEART were both safe and modestly effective in improving rule-out with single presentation hs-cTnT. However, the converse was true for hs-cTnI, with RSs ruling out considerably less patients than low level hs-cTnI alone.