While the use of high-sensitivity troponin testing increases our ability to distinguish risk, patients with myocardial injury (i.e., troponin elevation without acute signs of myocardial ischemia) or myocardial infarction type 2 (T2MI, imbalance between oxygen supply and demand) are often identified. Design: This prospective, pragmatic, multicenter, randomized study among patients with suspected demand ischemia leading to troponin elevation (n=1800, T2MI [1500], chronic myocardial injury [300]) compares the impact of invasive angiography (or CT angiography according to local preference) within 5 days of randomization versus conservative management (with or without functional testing at the physician's discretion) for all causes. The randomized treatment assignment will be stratified by the estimated mortality risk based on the APACHE III risk score.
Cost-effectiveness will be evaluated by follow-up of clinical events, quality of life and resource utilization over 24 months. Summary: Determining the most appropriate first-line screening strategy for these commonly encountered high-risk T2MI patients in a randomized comparative study will be crucial in informing evidence-based guidelines that lead to better patient and healthcare outcomes. Given this population's high comorbidity burden and competing cardiac and noncardiac risks, the primary endpoint will be all-cause mortality (ie, survival).
To focus on patients with a higher likelihood of supply-demand ischemia, enrollment of patients with chronic myocardial injury (pattern 2: See "Standardized risk assessment and troponin pattern") will be limited to n=300 and results will be exploratory in this. All enrolled patients will have their baseline Global Registries for Acute Cardiac Events (GRACE) risk score and Acute Physiology, Age and Chronic Health Evaluation (APACHE) III score. 10,11) Block randomization will be performed within strata, based on troponin pattern, predicted risk of in-hospital mortality (APACHE III), and hospital enrollment. In addition to the allocated management strategy and associated timelines, all other subsequent treatment, including secondary prevention, will be left to the discretion of the clinician.
The study will enroll hospitalized patients with at least one elevated (“rule-in”) troponin result (i.e.
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If invasive coronary angiography is chosen according to local practice, radial or femoral access will be permitted. Angiography performed outside the 5-day window will be considered a protocol breach, but these patients will be retained in the analysis. All patients will be followed to assess frequency of diagnostic procedures/services at initial presentation and during follow-up (eg, stress testing, echocardiography, invasive examination and revascularization), hospitalization costs/total length of stay (LOS), ambulatory health care (i.e. . general practitioners and specialists).
17) In-hospital costs will be covered by hospital billing systems, while out-of-hospital costs will be determined by the National Health Benefits List and the Prescribing Benefits List (ie Australia's Nationalized Health Financing System). A clinical event review committee independent of the study management team will provide blinded assessment (de-identified events for treatment group, hospital and patient details) of primary and secondary endpoints. The primary analysis population will be intention-to-treat, including all patients randomized to the study and reported according to the CONSORT guidelines.
An economic evaluation will be performed comparing the average results and incremental costs of invasive angiography with those of conservative treatment. To calculate QALYs, patient-level utility measures obtained from the EQ-5D 5L instrument will be integrated with survival curves using the quality-adjusted survival analysis (QASA) method. 18) Incremental costs associated with the two trial arms will be estimated using patient data obtained from the Medical Benefits Scheme (MBS), Pharmaceutical Benefits Scheme (PBS) and Australian Diagnostics Improvement Group (AR-DRG) cost weights. Run-time mean costs and outcomes between intervention and control groups will be compared, and incremental cost-effectiveness ratios (ICERs) will be presented with confidence intervals.
Uncertainty in the economic evaluation results will be taken into account through appropriate one-way and multi-way sensitivity analyses. Standardized evaluation of the pretest probability of non-coronary risk by the APACHE III score will inform the clinical translation of these results within the routine care of patients at high divergent risk. Independent and blinded assessment of the admission (index) diagnosis and clinical events will provide a robust evaluation of the clinical relevance of routine coronary examination for myocardial injury and type 2 MI.
Evolution in troponin assays has increased the complexity of clinical coronary risk assessment. Scottish Heart Computed Tomography, COURAGE: Clinical Outcomes Using Revascularization and Aggressive Drug Evaluations. The authors are solely responsible for the design and conduct of this study, including the study analyses, drafting, editing, and approval of the paper and its final content.
Patients with a previous angiogram within the last 6 months, regardless of the presence or absence of coronary artery disease documented on that investigation. CV mortality CV death will be defined as any death resulting from acute myocardial infarction (MI), cardiogenic shock, cardiac arrhythmia/sudden cardiac death, heart failure/acute pulmonary oedema, stroke, CV procedure, CV haemorrhage and any other cause of CV that is documented as an antecedent cause of death on the death certificate. New/recurrent MI* Acute myocardial injury with clinical evidence of acute myocardial ischemia and detection of increased and/or decreased cTn values of at least one value above the 99th percentile URL and at least one of the following;
All in-hospital MIs occurring during the index presentation will be excluded from the primary outcome.
