Background Acute coronary syndrome is a common medical emergency. The optimal strategy to investigate patients who are at intermediate risk of acute coronary syndrome has not been fully determined. Objective To investigate the role of early computed tomography coronary angiography in the investigation and treatment of adults presenting with suspected acute coronary syndrome. Design A prospective, multicentre, open, parallel-group randomised controlled trial with blinded end-point adjudication. Setting Thirty-seven hospitals in the UK. Participants Adults (aged ≥ 18 years) presenting to the emergency department, acute medicine services or cardiology department with suspected or provisionally diagnosed acute coronary syndrome and at least one of the following: (1) a prior history of coronary artery disease, (2) a cardiac troponin level > 99th centile and (3) an abnormal 12-lead electrocardiogram. Interventions Early computed tomography coronary angiography in addition to standard care was compared with standard care alone. Participants were followed up for 1 year. Main outcome measure One-year all-cause death or subsequent type 1 (spontaneous) or type 4b (stent thrombosis) myocardial infarction, measured as the time to such event adjudicated by two cardiologists blinded to the computerised tomography coronary angiography (CTCA) arm. Cost-effectiveness was estimated as the lifetime incremental cost per quality-adjusted life-year gained. Results Between 23 March 2015 and 27 June 2019, 1748 participants [mean age 62 years (standard deviation 13 years), 64% male, mean Global Registry Of Acute Coronary Events score 115 (standard deviation 35)] were randomised to receive early computed tomography coronary angiography (n = 877) or standard care alone (n = 871). The primary end point occurred in 51 (5.8%) participants randomised to receive computed tomography coronary angiography and 53 (6.1%) participants randomised to receive standard care (adjusted hazard ratio 0.91, 95% confidence interval 0.62 to 1.35; p = 0.65). Computed tomography coronary angiography was associated with a reduced use of invasive coronary angiography (adjusted hazard ratio 0.81, 95% confidence interval 0.72 to 0.92; p = 0.001) but no change in coronary revascularisation (adjusted hazard ratio 1.03, 95% confidence interval 0.87 to 1.21; p = 0.76), acute coronary syndrome therapies (adjusted odds ratio 1.06, 95% confidence interval 0.85 to 1.32; p = 0.63) or preventative therapies on discharge (adjusted odds ratio 1.07, 95% confidence interval 0.87 to 1.32; p = 0.52). Early computed tomography coronary angiography was associated with longer hospitalisations (median increase 0.21 days, 95% confidence interval 0.05 to 0.40 days) and higher mean total health-care costs over 1 year (£561 more per patient) than standard care. Limitations The principal limitation of the trial was the slower than anticipated recruitment, leading to a revised sample size, and the requirement to compromise and accept a larger relative effect size estimate for the trial intervention. Future work The potential role of computed tomography coronary angiography in selected patients with a low probability of obstructive coronary artery disease (intermediate or mildly elevated level of troponin) or who have limited access to invasive cardiac catheterisation facilities needs further prospective evaluation. Conclusions In patients with suspected or provisionally diagnosed acute coronary syndrome, computed tomography coronary angiography did not alter overall coronary therapeutic interventions or 1-year clinical outcomes, but it did increase the length of hospital stay and health-care costs. These findings do not support the routine use of early computed tomography coronary angiography in intermediate-risk patients with acute chest pain. Trial registration This trial is registered as ISRCTN19102565 and Clinical Trials NCT02284191. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 37. See the NIHR Journals Library website for further project information.

Background Acute kidney injury demonstrates a high incidence in critically ill populations, with many requiring renal replacement therapy. Patients may be at increased risk of acute kidney injury if prescribed certain potentially nephrotoxic medications. We aimed to evaluate this association in ICU survivors. Methods Study design – secondary analysis of national cohort of ICU survivors to hospital discharge linked to Scottish healthcare datasets. Outcomes: primary – renal replacement therapy in ICU; secondary – early acute kidney injury (calculated using urine output and relative change from estimated baseline serum creatinine within first 24 h of ICU admission using modified-RIFLE criteria). Primary exposure: pre-admission community prescribing of at least one potential nephrotoxin: angiotensin-converting-enzyme inhibitors/angiotensin-receptor blockers, diuretics or nonsteroidal anti-inflammatory drugs. Statistical analyses: unadjusted associations – univariable logistic regression; confounder adjusted: multivariable logistic regression. Results During 2011–2013, 12,838 of 23,116 patients (55.5%) were prescribed at least one community prescription of at least one nephrotoxin; 1330 (5.8%) patients received renal replacement therapy; 3061 (15.7%) had acute kidney injury. Patients exposed to at least one examined nephrotoxin experienced higher incidence of renal replacement therapy (6.8% vs 4.5%; adjOR 1.46, 95%CI 1.24, 1.72, p < 0.001) and acute kidney injury (19.8% vs 10.9%; adjOR 1.61, 1.44, 1.80, p < 0.001). Increased risk of RRT was also found for angiotensin-converting-enzyme inhibitors/angiotensin-receptor blockers (adjOR 1.65, 1.40, 1.94), non-steroidal anti-inflammatory drugs (adjOR 1.12, 1.02, 1.44) and diuretics (adjOR 1.35, 1.14, 1.59). Conclusions Community prescribing of potential nephrotoxins increases the risk of renal replacement therapy/early acute kidney injury in ICU populations. Analyses were limited by the survivor dataset and potential residual confounding. Findings add consistency to previous research improving understanding of the harmful potential of these important medications and their timely cessation in acute illness.