Simvastatin for patients with acute respiratory distress syndrome: long-term outcomes and cost-effectiveness from a randomised controlled trial.

BACKGROUND: Simvastatin therapy for patients with acute respiratory distress syndrome (ARDS) has been shown to be safe and associated with minimal adverse effects, but it does not improve clinical outcomes. The aim of this research was to report on mortality and cost-effectiveness of simvastatin in patients with ARDS at 12 months. METHODS: This was a cost-utility analysis alongside a multicentre, double-blind, randomised controlled trial carried out in the UK and Ireland. Five hundred and forty intubated and mechanically ventilated patients with ARDS were randomly assigned (1:1) to receive once-daily simvastatin (at a dose of 80 mg) or identical placebo tablets enterally for up to 28 days. RESULTS: Mortality was lower in the simvastatin group (31.8%, 95% confidence interval (CI) 26.1-37.5) compared to the placebo group (37.3%, 95% CI 31.6-43.0) at 12 months, although this was not significant. Simvastatin was associated with statistically significant quality-adjusted life year (QALY) gain (incremental QALYs 0.064, 95% CI 0.002-0.127) compared to placebo. Simvastatin was also less costly (incremental total costs -£3601, 95% CI -8061 to 859). At a willingness-to-pay threshold of £20,000 per QALY, the probability of simvastatin being cost-effective was 99%. Sensitivity analyses indicated that the results were robust to changes in methodological assumptions with the probability of cost-effectiveness never dropping below 90%. CONCLUSION: Simvastatin was found to be cost-effective for the treatment of ARDS, being associated with both a significant QALY gain and a cost saving. There was no significant reduction in mortality at 12 months, TRIAL REGISTRATION: ISRCTN, 88244364. Registered 26 November 2010.

The cost-effectiveness of cardiac computed tomography for patients with stable chest pain.

OBJECTIVE: To assess the cost-effectiveness of cardiac CT compared with exercise stress testing (EST) in improving the health-related quality of life of patients with stable chest pain. METHODS: A cost-utility analysis alongside a single-centre randomised controlled trial carried out in Northern Ireland. Patients with stable chest pain were randomised to undergo either cardiac CT assessment or EST (standard care). The main outcome measure was cost per quality adjusted life year (QALY) gained at 1 year. RESULTS: Of the 500 patients recruited, 250 were randomised to cardiac CT and 250 were randomised to EST. Cardiac CT was the dominant strategy as it was both less costly (incremental total costs -£50.45; 95% CI -£672.26 to £571.36) and more effective (incremental QALYs 0.02; 95% CI -0.02 to 0.05) than EST. At a willingness-to-pay threshold of £20 000 per QALY the probability of cardiac CT being cost-effective was 83%. Subgroup analyses indicated that cardiac CT appears to be most cost-effective in patients with a likelihood of coronary artery disease (CAD) of <30%, followed by 30%-60% and then >60%. CONCLUSIONS: Cardiac CT is cost-effective compared with EST and cost-effectiveness was observed to vary with likelihood of CAD. This finding could have major implications for how patients with chest pain in the UK are assessed, however it would need to be validated in other healthcare systems. TRIAL REGISTRATION NUMBER: (ISRCTN52480460); results.

A comparison of cardiac computerized tomography and exercise stress electrocardiogram test for the investigation of stable chest pain: the clinical results of the CAPP randomized prospective trial.

AIMS: To determine the symptomatic and prognostic differences resulting from a novel diagnostic pathway based on cardiac computerized tomography (CT) compared with the traditional exercise stress electrocardiography test (EST) in stable chest pain patients. METHODS AND RESULTS: A prospective randomized controlled trial compared selected patient outcomes in EST and cardiac CT coronary angiography groups. Five hundred patients with troponin-negative stable chest pain and without known coronary artery disease were recruited. Patients completed the Seattle Angina Questionnaires (SAQ) at baseline, 3, and 12 months to assess angina symptoms. Patients were also followed for management strategies and clinical events. Over the year 12 patients withdrew, resulting in 245 in the EST cohort and 243 in the CT cohort. There was no significant difference in baseline demographics. The CT arm had a statistical difference in angina stability and quality-of-life domains of the SAQ at 3 and12 months, suggesting less angina compared with the EST arm. In the CT arm, there was more significant disease identified and more revascularizations. Significantly, more inconclusive results were seen in the EST arm with a higher number of additional investigations ordered. There was also a longer mean time to management. There were no differences in major adverse cardiac events between the cohorts. At 1 year in the EST arm, there were more Accident and Emergency (A&E) attendances and cardiac admission. CONCLUSION: Cardiac CT as an index investigation for stable chest pain improved angina symptoms and resulted in fewer investigations and re-hospitalizations compared with EST. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN52480460.

Bone marrow micrometastases in esophageal carcinoma: a 10-year follow-up study.

Detection of bone marrow micrometastases (BMMs) in patients with esophageal carcinoma may indicate a metastatic phenotype. We assessed if the presence of BMMs had adverse prognostic significance in a 10-year follow-up study. Patients undergoing surgery for esophageal cancer were prospectively recruited between February 1999 and August 2000. Bone marrow aspirates were obtained from the iliac crest of patients under general anesthesia at the time of surgery. Immunocytochemical analysis using anticytokeratin antibodies CAM 5.2 and AE1/AE3 was undertaken to determine the presence of BMMs. Union International Contre le Cancer staging was recorded for all patients. Patient follow-up was completed over a 10-year period through analysis of the Northern Ireland Cancer Registry. Forty-two patients (male = 35) were included, with a mean age of 67.2 years (range 39-83). BMMs were detected in 19 patients (45.2%). International Contre le Cancer tumor staging was stage I = 6, stage II = 10, stage III = 24, and stage IV = 2. BMMs were associated with lymphovascular invasion (P= 0.02) and advanced T stage (P= 0.02). Overall, 10-year survival was 21.4% (n= 9), with a median follow-up of 877.5 days (interquartile range 391.5-2546.3). There was no statistically significant difference between the survival of patients with or without BMMs (1451.4 vs. 1431.6 days, P= 0.99). Univariate analysis demonstrated a trend toward decreased survival for patients with positive lymph nodes (P= 0.07), an increased T stage (P= 0.06), and lymphovascular invasion (P= 0.07). Multivariate analysis demonstrated that none of the variables were significant predictors of mortality. Although the presence of BMMs correlates with recognized adverse tumor characteristics in patients with esophageal cancer, micrometastases detected in the bone marrow at time of surgery does not influence long-term survival.