Losartan reduces the costs associated with diabetic end-stage renal disease: the RENAAL study economic evaluation

OBJECTIVE: To evaluate the within-trial effect of losartan and conventional antihypertensive therapy (CT) compared with placebo and CT on the economic cost associated with end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: The Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) study was a multinational double-blind randomized placebo-controlled clinical trial designed to evaluate the renal protective effects of losartan on a background of CT (excluding ACE inhibitors and angiotensin II receptor agonists [AIIAs]) in patients with type 2 diabetes and nephropathy. The primary composite end point was doubling of serum creatinine, ESRD, or death. Data on the duration of ESRD were used to estimate the economic benefits of slowing the progression of nephropathy. The cost associated with ESRD was estimated by combining the days each patient experienced ESRD with the cost of ESRD over time. The cost of ESRD for individuals with diabetes was estimated using data from the U.S. Renal Data System. Total cost was estimated as the sum of the cost associated with ESRD and the cost of study therapy. RESULTS-We estimated that losartan and CT compared with placebo and CT reduced the number of days with ESRD by 33.6 per patient over 3.5 years (P = 0.004, 95% CI 10.9-56.3). This reduction in ESRD days resulted in a decrease in cost associated with ESRD of 5144 US dollars per patient (P = 0.003, 95% CI 1701 to 8587 US dollars). After accounting for the cost of losartan, the reduction in ESRD days resulted in a net savings of 3522 US dollars per patient over 3.5 years (P = 0.041, 143 to 6900 US dollars). CONCLUSIONS: Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the incidence of ESRD, but also resulted in substantial cost savings.     

Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date

Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow- up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries.      

Psoriasis and diabetes: a population-based cross-sectional study

Background Previous reports have shown an association between psoriasis and the metabolic syndrome, but there are only a few studies on the association between psoriasis and diabetes. Objectives To study the association between psoriasis and diabetes. Methods A cross‐sectional study was performed utilizing the database of Clalit Health Services (CHS). Patients who were diagnosed with psoriasis were compared with CHS enrolees without psoriasis regarding the prevalence of diabetes. Patients with diabetes were identified using the CHS chronic diseases registry. Chi‐squared tests were used to compare categorical parameters. Logistic regression models were used for multivariate analyses. Results The study included 16 851 patients with psoriasis and 74 987 subjects without psoriasis (control patients). The proportion of diabetes was significantly higher in patients above 35 years (P < 0.05). The age‐adjusted proportion of diabetes was significantly higher in psoriasis patients as compared to the control group [odds ratio (OR), 1.38, P < 0.05] and was similar in men and women (OR, 1.32, 1.45, respectively). A multivariate logistic regression model showed that psoriasis was significantly associated with diabetes, independently of age and gender (OR, 1.58, P < 0.001). Conclusions Our study supports previous reports of an association between psoriasis and diabetes. Dermatologists taking care of patients with psoriasis should be aware of this association and advise the patients to reduce additional risk factors such as smoking, hypertension or dyslipidemia.     

Theoretical and methodological considerations in the measurement of spasticity

Purpose: To discuss the measurement of spasticity in the clinical and research environments, make recommendations based on the SPASM reviews of biomechanical, neurophysiological and clinical methods of measuring spasticity and indicate future developments of measurement tools. Method: Using the results of the systematic reviews of the biomechanical, neurophysiological and clinical approaches, methods were evaluated across three dimensions: (1) validity, reliability and sensitivity to change; (2) practical quality such as ease of use and (3) qualities specific to the measurement of spasticity, for example ability to be applied to different muscle groups. Methods were considered in terms of applicability to research and clinical applications. Results: A hierarchy of measurement approaches was identified from highly controlled and more objective (but unrelated to function) to ecologically valid, but less objective and subject to contamination from other variables. The lack of a precise definition of spasticity may account for the problem of developing a valid, reliable and sensitive method of measurement. The reviews have identified that some tests measure spasticity per se, some phenomena associated with spasticity or consequential to it and others the effect of spasticity on activity and participation and independence. Conclusions: Methods appropriate for use in research, particularly into the mechanism of spasticity did not satisfy the needs of the clinician and the need for an objective but clinically applicable tool was identified. A clinical assessment may need to generate more than one 'value' and should include evaluation of other components of the upper motor neurone syndrome. There is therefore a need for standardized protocols for 'best practice' in application of spasticity measurement tools and scales.     

Effects of Losartan-based therapy on the incidence of end-stage renal disease and associated costs in type 2 diabetes mellitus: A retrospective cost-effectiveness analysis in the United Kingdom

Background:

In the Reduction of Endpoints in Non-Insulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study, the primary composite end point was the 2-fold increase in baseline serum creatinine concentration, the development of end-stage renal disease (ESRD), or death. The effects of losartan used for the prevention or delay of progression of diabetic nephropathy to ESRD were compared with those of conventional anti-hypertensive treatment (control) (calcium channel blockers, diuretics, α-blockers, β-blockers, and centrally acting agents), but not angiotensin-converting enzyme (ACE) inhibitors or angiotensin II antagonists (AIIAs), in 1513 adults with type 2 diabetes mellitus (DM-2) and nephropathy. Both treatment groups received conventional antihypertensive therapy (calcium channel blockers, diuretics, α-blockers, β-blockers, and/or centrally acting agents). ACE inhibitors and AIIAs were not allowed during the study period. The relative risk (RR) for composite outcome was 25% less, and the RR for ESRD was 28% less, in the losartantreated group compared with the control group.

Objective:

The aim of this retrospective cost-effectiveness analysis was to use data from the RENAAL study to determine the survival benefits and lifetime direct medical costs of a losartan-based regimen for the prevention of ESRD in patients with DM-2 and nephropathy in the setting of the UK National Health Service (NHS).

Methods:

This analysis used life-years saved as the effectiveness measure. The effect of losartan-based treatment on ESRD risk was confined to the trial period (3.5 years). However, survival and the lifetime direct medical costs of managing ESRD were projected beyond the trial period to incorporate the full effects of ESRD on survival and resource use. The effect of altering key variables was examined using 1-way sensitivity analyses.

Results:

ESRD-related costs were significantly lower in patients receiving losartan-based treatment compared with those in the control group (savings per patient, 7390 [95% CI, 11,366-3414; P< 0.001] [1 = US −$1.75]). Incorporation of the cost of losartan into the assessment found reduced net costs (savings per patient, 6622 [95% CI, 10,591-2653; P= 0.001]). The projected mean number of life years saved due to ESRD risk reduction with losartan was 0.44 years (95% CI, 0.16-0.71; P = 0.002). Losartan treatment was found to save costs in all cases, even if the cost of renal replacement therapy for patients with ESRD was reduced by 50%.

Conclusion:

In this retrospective cost-effectiveness analysis using data from the RENAAL study, losartan-based treatment for the prevention or delay of progression of diabetic nephropathy to ESRD in patients with DM-2 and nephropathy was found to be potentially cost saving compared with conventional anti-hypertensive therapy from the perspective of the UK NHS.