Use of High-Sensitivity Cardiac Troponin in Patients With Kidney Impairment

This randomized clinical trial examines the use of high-sensitivity cardiac troponin testing for patients with kidney impairment.

on sex-specific 99 th centile upper reference limits of 16 ng/L for women and 34 ng/L for men. (4) Adjudication of the diagnosis of myocardial infarction Type 1 myocardial infarction was defined as myocardial necrosis (any hs-cTnI concentration above the 99th centile with a rise and/or fall in hs-cTnI concentration where serial testing was performed) in the context of a presentation with suspected acute coronary syndrome with symptoms or signs of myocardial ischemia on the electrocardiogram. Type 4b myocardial infarction was defined as myocardial injury with symptoms or signs of myocardial ischemia secondary to stent thrombosis demonstrated on coronary angiography.

Outcomes
All trial data were collected from routine electronic regional and national healthcare datasets, linked, anonymized and held securely within the NHS National Services Scotland national safe haven. All in-hospital and community deaths, and all hospital admissions are recorded on the Register of Deaths in Scotland and the Scottish Morbidity Record (SMR) respectively.
All attendances across any participating hospital where cardiac troponin was measured and the high-sensitivity cardiac troponin I concentration was above the 99 th centile were reviewed and the diagnosis adjudicated. We used the same approach to adjudication as for the index hospital episode with the panel blinded to all cardiac troponin measurements during the index episode and to the study phase.
The primary outcome was myocardial infarction (type 1 or type 4b) or cardiovascular death at revascularization, cardiovascular death, all-cause death, duration of stay, hospitalization for heart failure and ischemic stroke. Secondary safety end-points include major hemorrhage, unplanned hospitalization excluding acute coronary syndrome, and non-cardiovascular death.
Unplanned coronary revascularization was defined as any urgent or emergency percutaneous coronary intervention or coronary artery bypass grafting following discharge. International Classification of Disease (ICD)-10 codes from the Scottish Morbidity Record were used to define hospitalization for heart failure (I50) and ischemic stroke (I63, I65, or I66). Bleeding was defined according to the Bleeding Academic Research Consortium (BARC) definition using ICD-10 and OPCS codes to classify each bleeding event as previously described. (5,6) Major hemorrhage was defined as BARC type 3 or type 5. Unplanned hospitalization excluding acute coronary syndrome was defined as any hospital attendance or admission excluding type 1 or type 4b myocardial infarction at 30 days.

Statistical analysis
A total of 48,282 consecutive patients with suspected acute coronary syndrome were enrolled across ten hospitals (Supplementary figure 1) [n=9,080] renal impairment). The primary outcome was compared before and after implementation of the high-sensitivity assay in patients with high-sensitivity cardiac troponin concentrations above the 99th centile, stratified by eGFR (<60 and ≥60 ml/min/1.73m 2 ), using two identical Cox regression models. This model included all variables from the primary analysis of the High-STEACS trial. (1) However, as patients with renal impairment were significantly older and had more comorbidities than patients with normal renal function, we included additional adjustment for comorbidities, in accordance with the STROBE hospital site (fitted as a random effect), seasonality, time of presentation from the start date of the trial, prior diabetes mellitus, ischemic heart disease or cerebrovascular disease, highsensitivity cardiac troponin I concentration (log-transformed) and social deprivation status (SIMD quintile). All statistical analyses were performed using R, version 3.6.1 (R Foundation, Vienna, Austria).

Ethical approval and statement of data transparency
The trial was conducted in accordance with the Declaration of Helsinki and with the approval of the Scotland Research Ethics Committee, the Public Benefit and Privacy Panel for Health and Social Care and each National Health Service Health Board. As randomization was at the hospital level, individual patient consent was not sought. The High-STEACS trial makes use of multiple routine electronic health care data sources that are linked, de-identified and held in our national safe haven, which is accessible by approved members of the research team who have undertaken the necessary governance training. Summary data and source analysis code can be made available upon request to the corresponding author (nick.mills@ed.ac.uk).