Systematic review, meta-analysis and economic modelling of ...

Discussionneed for revascularisation. There was evidence from some studies that death and MI rates were higheramong patients with positive ETT, although the modest numbers limit the conclusions that may be drawn.No studies reported multivariate analysis to determine whether exercise ECG added to the prognostic valueof routine clinical assessment, including ECG and troponin, although most of the studies excluded patientswith diagnostic ECG changes.Cost-effectiveness of presentation biomarker strategies for myocardial infarctionWe developed a decision-analysis model to compare different strategies for using biomarkers atpresentation with a no testing (discharge all home) and delayed troponin (admit and measure troponinat 10 hours) strategies. We tested presentation TnT using either the 10% CV or 99th percentile as thediagnostic threshold and using a high-sensitivity assay with the 99th percentile as the diagnostic threshold.We selected these strategies because the estimates from our meta-analysis would allow us to investigatethe effect of varying the diagnostic threshold on sensitivity and specificity, and thus on cost-effectiveness.We tested the strategies in various scenarios to examine whether (1) the presence or absence of knownCAD and (2) the inpatient management, in terms of access to a decision-making doctor, influenced costeffectiveness.We also tested presentation high-sensitivity TnI instead of HsTnT, because the point estimateof sensitivity was lower and specificity higher in our meta-analysis, and a 3-hour high-sensitivity troponinstrategy, because recent analysis suggests that this improves sensitivity but provides a strategy that can beapplied without hospital admission.The results showed that, as expected, effectiveness (QALYs) increased with increasing sensitivity and costsincreased with decreasing specificity. In all but one scenario a strategy of measuring HsTnT at presentation(with admission for a 10-hour troponin testing if positive and discharge home if negative) was the optimalstrategy. It was the most effective strategy among those with an ICER of < £20,000–30,000/QALY. The10-hour troponin testing was more effective, but had an ICER that exceeded the £30,000/QALY threshold.In one scenario the 10-hour troponin strategy may have been optimal, i.e. if the patient did not haveknown CAD, a doctor was available on demand to discharge the patient when the 10-hour troponin levelwas measured and the £30,000/QALY threshold was used.These findings suggest that in most circumstances delaying troponin measurement until 10 hours isunlikely to represent a cost-effective use of NHS resources. The exception to this may be a setting wherethe decision-making is efficient enough to ensure that patient discharge can occur as soon as the 10-hourtroponin result is available. However, there are a number of assumptions in the model that need to betaken into account when interpreting these findings, two of which were explored in sensitivity analysis.Our meta-analysis suggested that presentation HsTnT has sensitivity of 96%, but this was based on onlytwo studies. The uncertainty around the estimate was reflected in the wide predictive interval around thisestimate, which was used in the cost-effectiveness modelling. If this is an overestimate of sensitivity, thenwe will have underestimated the comparative cost-effectiveness of the 10-hour troponin strategy. This issupported by our sensitivity analysis using estimates for the ADVIA Centaur Ultra troponin I assay insteadof Roche HsTnT. When the lower estimate of sensitivity was used for presentation high-sensitivity troponin(and higher estimate of specificity), the 10-hour troponin strategy was more likely to be cost-effective.However, it was still likely to be optimal in only one scenario if the £20,000/QALY threshold were used andin three scenarios if the £30,000/QALY threshold were used.Our main analysis also assumed that the only alternative strategies were presentation troponin or 10-hourtroponin testing because these were the strategies with the best supporting data at the time the studywas planned. However, a recent analysis suggested that measuring troponin at presentation and 3 hourslater could optimise sensitivity yet still provide a strategy that does not require hospital admission in mostcases. When we tested the 3-hour strategy in a sensitivity analysis, we found that it was optimal in allscenarios at both the £20,000/QALY and £30,000/QALY threshold, whereas the 10-hour strategy was notcost-effective in any scenario using either threshold. This suggests that high-sensitivity troponin measured110NIHR Journals Library