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Direct Comparison of the 0/1h and 0/3h Algorithms for Early Rule-Out of Acute Myocardial Infarction

and for the APACE Investigators
Originally publishedhttps://doi.org/10.1161/CIRCULATIONAHA.118.034260Circulation. 2018;137:2536–2538

    Patients with symptoms suggestive of acute myocardial infarction (AMI) account for ≈10% of all emergency department (ED) presentations.1 The majority of patients are finally found to have diagnoses other than AMI.2 Thus, the expeditious evaluation of such patients is important because delays in ruling out AMI may interfere with the detection of other underlying diseases. The 0/1 hour (0/1h) algorithm and the 0/3 hour (0/3h) algorithm are both recommended by the European Society of Cardiology with a Class I recommendation for the early rule-out of AMI.1 The 0/1h algorithm and 0/3h algorithm are completely different protocols. Whereas the 0/1h algorithm uses high-sensitivity cardiac troponin (hs-cTn) concentrations at presentation and absolute changes within the first hour and hence takes optimal advantage of the increased diagnostic accuracy and precision of hs-cTn assays, the 0/3h algorithm uses a fixed threshold protocol based on the 99th percentile at presentation and 3 hours in conjunction with clinical criteria (GRACE [Global Registry of Acute Coronary Events] score <140 and the need to be pain free). It is currently unknown whether 1 algorithm is preferable to the other.

    The aim of this study was to directly compare safety, quantified by the negative predictive value (NPV) and the negative likelihood ratio (LR) for the presence of AMI, and efficacy, quantified by the proportion of patients triaged toward rule-out in a large diagnostic multicenter study enrolling patients presenting with suspected AMI to the ED (URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587). The study was carried out according to the principles of the Declaration of Helsinki and approved by the local ethics committees. Written informed consent was obtained from all patients. Patients presenting with ST-segment–elevation MI were excluded. Triage toward rule-out by the 0/1h or the 0/3h algorithm was compared against the final adjudication performed by 2 independent cardiologists using all information, including cardiac imaging and serial hs-cTnT measurements. Analyses were performed with hs-cTnT and hs-cTnI. NPV and efficacy were compared by the McNemar test and Pearson χ2 test, respectively. The 95% confidence intervals (CIs) were calculated with the Wilson score method without continuity correction.

    Among 2547 patients eligible for analysis with hs-cTnT, AMI was the final adjudicated diagnosis in 387 patients (15%). The 0/1h algorithm provided safety similar to that of the 0/3h algorithm (NPV, 99.8% [95% CI, 99.4–99.9] and negative LR, 0.01 [95% CI, 0.00–0.03] versus NPV, 99.7% [95% CI, 99.2–99.9] and negative LR, 0.02 [95% CI, 0.00–0.05]) but allowed the rule-out of significantly more patients compared with the 0/3h algorithm (60% versus 44%; P<0.001). Among 2197 patients eligible for analysis with hs-cTnI, AMI was the final diagnosis in 327 patients (15%). The 0/1h algorithm provided higher safety compared with the 0/3h algorithm (NPV, 99.6% [95% CI, 99.1–99.9%] and negative LR, 0.02 [95% CI, 0.01–0.05] versus NPV, 97.8% [95% CI, 96.7–98.5] and negative LR, 0.13 [95% CI, 0.09–0.19]) and allowed the rule-out of a similar portion of patients compared with the 0/3h-algorithm (52% versus 51%; P=0.507; Figure).

    Overall, 711 patients (28%) presented within the first 2 hours from chest pain onset. Safety for the 0/1h and 0/3h algorithms with hs-cTnT was very high (NPV, 99.6% [95% CI, 98.4–99.9] versus 100% [95% CI, 98.9–100]) and comparable to late presenters (chest pain onset >2 hours) with 99.9% (95% CI, 99.5–100) versus 99.6% (95% CI, 98.9–99.9), respectively. The 0/1h algorithm allowed the rule-out of more patients compared with the 0/3h algorithm in early presenters (64% versus 49%; P<0.001) and in late presenters (59% versus 42%; P<0.001). Findings were confirmed with hs-cTnI and with 30-day survival used as an additional outcome measure for safety, with survival rates of 99.9% to 100% for patients triaged toward rule-out by both algorithms.

    These findings corroborate and extend previous work on the development and validation of safe and effective rule-out strategies for AMI and have important clinical implications.35 The excellent safety achieved with both algorithms documents the suitability of most of these patients for early discharge and outpatient management. Beyond the more favorable combination of safety and efficacy by the 0/1h algorithm versus the 0/3h algorithm, the following features may help physicians and institutions in the selection of their preferred triage algorithm. First, the 0/1h algorithm has the obvious and important additional advantage of allowing clinical decision making 2 hours earlier compared with the 0/3h algorithm. Because most patients triaged toward early rule-out are also candidates for direct discharge from the ED, it is very likely that it will reduce time to discharge and treatment cost in the ED. Second, the 0/1h algorithm does not require the use of a specific risk score, which further increases its feasibility. Previous studies have documented that omitting any of the 3 elements of the 0/3h algorithm (hs-cTn, GRACE score, pain-free criterion) in an effort to simplify the approach would worsen its safety and is therefore discouraged. Third, when putting our findings into clinical perspective, it is important to highlight that the 0/1h algorithm and the 0/3h algorithm should always be used in conjunction with all clinical information available. This is of paramount importance because, among patients presenting with acute chest discomfort to the ED, the rule-out of AMI is related to the possibility of rapid discharge and outpatient management but not identical to it.

    In conclusion, the 0/1h algorithm is superior to the 0/3h algorithm using hs-cTnT as well as hs-cTnI because it more favorably combines safety with efficacy.

    Figure.

    Figure. Direct comparison of the 0/1h and 0/3h algorithms for early rule-out of AMI using hs-cTnT (A) and hs-cTnI (B). The figure illustrates both coprimary end points: safety, as quantified by the negative predictive value (NPV; percent), and efficacy (proportion of patients assigned to ruled out; percent). Bars represent 95% confidence intervals. AMI indicates acute myocardial infarction; and hs-cTn, high-sensitivity cardiac troponin.

    Appendix

    Additional APACE Investigators: Zaid Sabti; Ivo Strebel; Samyut Shrestha; Dayana Flores; Michael Freese; Claudia Stelzig; Caroline Kulangara; Kathrin Meissner; Nicolas Schaerli; Deborah Mueller; Ana Yufera Sanchez; Lorraine Sazgary; Stella Marbot; Carolina Fuenzalida; Sofia Calderón; Esther Rodriguez Adrada; Damian Kawecki; Ewa Nowalany-Kozielska; Jiri Parenica; Eva Ganovská; Arnold von Eckardstein; Jens Lohrmann; Wanda Kloos; Stefan Osswald; Andreas Buser; Roland Bingisser; Nicolas Geigy.

    Footnotes

    *Drs Badertscher and Boeddinghaus contributed equally.

    http://circ.ahajournals.org

    Data sharing: The data, analytical methods, and study materials will not be made available to other researchers for purposes of reproducing the results or replicating the procedure.

    Christian Mueller, MD, Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail

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