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This study aimed to evaluate the impact of the risk minimisation measures issued by the European Medicines Agency in 2014 to restrict the combined use of renin–angiotensin system (RAS) blocking agents in Denmark. Data from the Danish National Prescription Registry covering all medications dispensed during January 2008–December 2018 was used. The outcome was monthly prevalence of patients codispensed RAS blockers. Autoregressive integrated moving average interrupted time series regression was used to evaluate dispensing trends. The prevalence of patients codispensed RAS blockers decreased from 0.01 to 0.0003%. Preintervention trend was declining and further decreased with an additional −0.45 (95% confidence interval −0.66, −0.25) codispensing per million population after the intervention. Overall, the intervention had minimal impact on the combined use of RAS blockers. However, as the combined use of RAS blockers is low, further interventions to restrict the combined use of RAS blockers may not be required in Denmark at this point. [ABSTRACT FROM AUTHOR]

Background: Angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin-receptor blocker (ARB) users may be associated with increased mortality in patients with post-operative acute kidney injury (AKI), but data are limited. We studied whether users of ACE-I/ARBs with AKI after colorectal cancer surgery (CRC) were associated with increased 1-year mortality after AKI.Methods: This population-based cohort study in Northern Denmark included patients with AKI within 7 days after CRC surgery during 2005-2014. From reimbursed prescriptions, patients were classified as ACE-I/ARB current, former, or non-users. We computed the cumulative 30-day and 1-year mortality after AKI with 95% confidence intervals (95% CI) using the Kaplan-Meier method (1-survival function). Hazard ratios (HRs) comparing mortality in current and former users with non-users were computed by Cox proportional hazards regression analyses, controlling for potential confounders.Results: We identified 10 713 CRC surgery patients. A total of 2000 patients had AKI and were included. Thirty-day mortality was 16.5% (95% CI 13.7-19.8), 16.2% (95% CI 11.3-22.8), and 13.4% (95% CI 11.6-15.4) for current, former, and non-users. Adjusted HR was 1.26 (95% CI 0.96-1.65) and 1.19 (95% CI 0.78-1.82) for current and former users compared with non-users. One-year mortality rates were 26.4% (95% CI 22.9-30.4), 29.8% (95% CI 23.2-37.8), and 24.7% (95% CI 22.4-27.2) in current, former, and non-users. Compared with non-users, the adjusted 1-year HR for death in current and former users were 1.29 (95% CI 0.96-1.73) and 1.11 (95% CI 0.91-1.35).Conclusion: Based on our findings, current users of ACE-I/ARB may possibly have a small increase in mortality rate in the year after post-operative AKI, although the degree of certainty is low. [ABSTRACT FROM AUTHOR]

Background: Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this state of vasodilation and pulmonary dysfunction including increased exhaled NO concentrations. Circulating metabolites (NO(x)) may affect the systemic and pulmonary NO-generation. However, the relations of these abnormalities to the haemodynamic changes remain unclear., Aims: The aims of the present study were to measure changes in exhaled NO in relation to circulating NO(x), RAAS, and haemodynamics., Methods: Twenty patients (eight child class A and 12 class B patients) underwent a liver vein catheterization with determination of splanchnic and systemic haemodynamics. Circulating NO(x) and exhaled NO were determined in the supine and sitting positions and related to haemodynamics, RAAS and lung diffusing capacity (D(L)CO). Eight matched healthy individuals served as controls., Results: All patients with cirrhosis had portal hypertension. We found no significant difference in exhaled NO between patients and controls and no changes from the supine to the sitting position. Exhaled NO in the patients correlated significantly with plasma volume, heart rate and D(L)CO. NO(x) concentrations were not significantly increased in the patients. NO(x) correlated with portal pressure and haemodynamic indicators of vasodilatation, but not with exhaled NO concentrations., Conclusion: In patients with moderate cirrhosis, exhaled NO is normal. Circulating NO(x) do not seem to reflect pulmonary and systemic NO release, but NO(x) seems to reflect systemic and splanchnic haemodynamic changes in cirrhosis., (© 2011 John Wiley & Sons A/S.)