Decreasing time to diagnosis in patients with acute chest pain: The incremental cost-effectiveness of implementing a multiple biomarker assay for early exclusion of NSTEMI

PURPOSE Because of the increasing pressure on healthcare budgets, it is desirable to investigate the incremental cost-effectiveness of new diagnostic opportunities prior to their implementation in practice. A likely waste of resources in healthcare, is assumed to occur at cardiology departments. Patients presenting with chest pain at the coronary pain unit (CPU), without elevation of the ST-segment on an ECG, are considered at risk of having an acute myocardial infarction (AMI), specifically a non ST-elevation myocardial infarction (NSTEMI). However, only a small proportion of these patients ultimately receive this clinical diagnosis. Because serial blood measurements are currently necessary to exclude NSTEMI, the majority of patients stay at the CPU several hours before being discharged. Since one day admission at the CPU costs €1241, research should aim at decreasing admission times. This study will examine whether implementing a multimarker assay, consisting of a myeloperoxidase (MPO), copeptin, and high-sensitive troponin measurement, is cost-effective compared to the current serial high-sensitive troponin measurement in patients presenting with chest pain at the CPU. METHOD Semi-structured interviews with four cardiologists were performed to analyze the extent to which their decision making is influenced by a patient‟s troponin result. Then, the performance of a high-sensitive troponin assay only, as well as the multimarker assay were estimated based on a systematic review of the available literature. These performances were used as input for a closed-ended questionnaire. Cardiologist were provided a range of analytical performances, reported as sensitivity, and the percentage of false negative results. Subsequently, ten cardiologists were asked to estimate the influence of a multimarker assay, with higher analytical performance than the current high-sensitive troponin assay, on their decision making. This influence considers the estimated percentages of patients discharged at each time point, and the number of (diagnostic) activities performed. The incremental cost-effectiveness ratio (ICER) was calculated for three different implementation strategies of the multimarker assay, each divided in three scenarios according to the analytical performance of the assays. Incremental cost-effectiveness of each scenario was illustrated using a cost effectiveness plane. Following this, one-way sensitivity analysis and best worst case analyses were performed to examine the robustness of the model for differences in input variables. RESULT Interviews revealed three issues with the current troponin assay. First, the consequence of a high-sensitive assay is that minor elevations in troponin can be observed in patients without NSTEMI. Secondly, serial measurements are therefore required to determine a change in troponin level, which is indicative of NSTEMI. Third, biomarkers are only of limited importance in setting the diagnosis, relative to a patient‟s clinical symptoms and ECG findings. Results of the questionnaire indicate that implementing a multimarker assay, with a sensitivity and negative predictive value (NPV) of both 99%, combined with additional troponin measurements after two and six hours, might result in cost savings of €191.18 per patient, and 130 earlier patient discharges. Assuming both a lower sensitivity (90 or 95%) and NPV (96 or 98%), this specific multimarker strategy remains dominant compared to the current serial troponin measurement. Sensitivity analysis revealed that the variation in cost of the multimarker assay strongly influence the ICER. However, in case of a multimarker assay with a sensitivity and NPV of 99%, combined with two additional troponin measurements, costs of MPO and copeptin together may raise up to €200.63 (including AMI-patients), to retain an equally cost-effective strategy as the current serial troponin measurement. CONCLUSION Because this study concerns an early economic evaluation, involving relatively much uncertainty in input variables, results have to be interpreted cautiously. However, assuming that the multimarker has a higher analytical performance than a high-sensitive troponin measurement only, we recommend the implementation of this multimarker assay with additional troponin measurements after two and six hours.