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Unlabelled: Glucose lowering medication use among patients with type 2 diabetes and advanced renal disease (eGFR<60) in a large multinational outcome trial (TREAT) is assessed. We demonstrate statistically significant differences regionally in use of metformin at lower eGFR and increasing reliance upon insulin with/without other medications at low eGFR.Introduction: As renal disease advances, most of the oral anti-diabetic agents requiring renal clearance must be reduced or discontinued. The potential for prolonged hypoglycemia, fluid/volume overload and congestive heart failure may complicate medication choices. In order to evaluate patterns of glycemia management we describe glucose lowering medication use among patients with advanced renal disease and type 2 diabetes in a large multinational outcome trial designed to focus on patients with eGFR<60 in order to commence a dialog on best practices. We felt that analysis of this data would be able to describe regional variations in treatment within a multinational trial in order to understand potential outcome differences attributed to complications.Results: The patients entering this study had moderate glycemic control. Insulin therapy either alone (32%) or in combination with other agents (17%) reflected a shift towards insulin use in those subjects with decreased renal function when compared with standard populations with normal kidney function. The use of multiple oral agents, or oral agents plus insulin was quite common. While gender did not appear to play a role in medication choices, there were significant regional variations. For example, oral agents were used more in North America compared with other regions (Latin America, Australia/Western Europe, Russia/Eastern Europe). Patients enrolled at more advanced ages were less likely to be on a regimen of rapid-acting insulin alone consistent with recommendations that suggest a preference for longer-acting preparations in the geriatric population (1). Higher degrees of obesity were associated more complex treatment regimens. Despite this population being at high risk for cardiovascular events, the use of beta blockers (50%), statins (64%) and aspirin (48%) were relatively low, especially in the group that did not require medications to achieve adequate glycemic control.Conclusions: Current attempts to compare strategies for diabetes therapy must control for baseline demographic group differences influencing treatment choice. Future recommendations for glycemic control in patients with Grade 3 or higher chronic kidney disease require additional studies, with matched populations. We suggest that evaluation of studies similar to TREAT will assist in determining the optimal therapeutic regimens for populations with moderate to severe renal dysfunction, a condition in which repeated hospitalizations for fluid overload/heart failure add to the high cost of diabetes care. [ABSTRACT FROM AUTHOR]

Background: Prior hospitalized heart failure (HF) trials have specified enrollment early after admission. This requirement is intended to capture a particular patient profile, but may be a barrier to efficient trial enrollment and retention. ASTRONAUT was the only phase III hospitalized HF trial with no such requirement, and allows comparison of patients randomized at various points during hospitalization. Methods: The ASTRONAUT trial randomized 1,615 patients hospitalized for HF with ejection fraction ≤40% to long-term use of aliskiren or placebo in addition to standard care. The present analysis compared patient profile, rates of protocol non-completion, and clinical outcomes by quartile of time from hospital admission to randomization. Per protocol, patients could be randomized at any time prior to hospital discharge after ≥6 hours of hemodynamic stability. Results: Median time to enrollment was 5 days (interquartile range [IQR] 3-8 days) and ranged from <1 day to 47 days. Time to enrollment varied by geographic region, with shortest times in North America (median 2 [IQR 2-4] days) and longest times in Eastern Europe (median 6 [IQR 3-9] days) (P <0.01). With few exceptions, baseline patient characteristics were similar by time to randomization quartile (Table). Rates of protocol non-completion were low and comparable across quartiles. There were no significant differences in rates of all-cause mortality or composite of cardiovascular mortality or HF hospitalization at 12 months by time to randomization quartile. Conclusion: In this clinical trial of patients hospitalized for HF, timing of randomization varied by geographic region. Patients randomized early and late during hospitalization had similar baseline characteristics and similar rates of protocol completion and trial endpoints. [ABSTRACT FROM AUTHOR]

Background: Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas)., Methods and Results: To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P<0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone., Conclusions: This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00094302., (© 2014 American Heart Association, Inc.)