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Following the recent Ongoing Telmistartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) finding of adverse renal outcomes, dual renin-angiotensin blockade has fallen out of favour, despite antihypertensive and antiproteinuric efficacy. However, in high-risk severe hypertension, not studied in ONTARGET, whether combination treatment should be withheld or withdrawn is not clear. We examine the renal effects of angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) monotherapy versus combination therapy in patients with type 2 diabetes and varying degrees of hypertension. Subjects attending a hospital diabetes centre were selected as case (combination therapy, n = 120) and control (monotherapy, n = 480). Subjects were matched for age, gender, ethnicity, estimated glomerular filtration rate (eGFR), blood pressure (BP) and study duration. Patients were stratified by BP, hypertension stage 1 (BP < 160/100, n = 506) and stage 2 (≥160/100, n = 94), and by treatment group. Data were analysed for the primary renal outcome of eGFR decline ≥20 ml/min, over a median of 3.7 years. In keeping with the ONTARGET study, for stage 1 hypertension, combination treatment is significantly worse than monotherapy for the primary outcome of eGFR decline ≥20 ml/min (20 vs. 10.7%, p = 0.01). In contrast, for stage 2 hypertension, this endpoint was reached less often for combination versus monotherapy (12.0 vs. 23.2%, p = 0.2). Combination treatment was also not detrimental in patients with proteinuria or eGFR < 60 ml/min and was associated with fewer macrovascular events. Given that hypertension control is paramount and in the spirit of primum non nocere, these data are reassuring should clinicians choose to use ACE-I and ARB combination therapy in the very hypertensive diabetic patient. [ABSTRACT FROM AUTHOR]

Date written: April 2009 Final submission: April 2009 [ABSTRACT FROM AUTHOR]

Date written: April 2009 Final submission: April 2009 [ABSTRACT FROM AUTHOR]

Aims: This retrospective study aimed to investigate both established and less well-explored factors as potential predictive variables for failed and delayed ulcer healing. Methods: Patients with type 1 or 2 diabetes with foot ulceration presenting consecutively to, and then subsequently managed at, a multidisciplinary, high-risk foot clinic were followed until ulcer healing, amputation or death. Data comprised prospective standardised documentation at each visit and retrospective collection from hospital records, and included patient demographics, comorbidities, laboratory variables, and ulcer infection, depth and area at each presentation. Multiple regression analysis was used to determine independent predictors of failure to heal and delayed healing. Results: Of the 107 consecutive patients studied, 95 (89%) healed overall, 50 (47%) had healed in 12 weeks and the mean healing rate was a 10% decrease in ulcer area per week. Amongst all variables examined, comorbid congestive heart failure (CHF) was the only factor independently predictive of all measured outcomes of failure to heal overall, delayed healing at 12 weeks, and reduced healing rate. Ulcer infection at presentation, longer duration of antibiotic use, and liver enzyme abnormalities of raised ALT and AST:ALT < 1 (each suggestive of non-alcoholic fatty liver disease), were also predictive of poor ulcer outcomes. Conclusions: Comorbid congestive cardiac failure is predictive of delayed foot ulcer healing rate as well as a lower probability of healing overall. Liver enzyme abnormalities also predicted delayed ulcer healing outcomes. The mechanisms underlying these associations with foot ulcer outcomes in diabetes are unclear. Further studies are needed to determine the role of systematic routine documentation of heart failure and its severity, and then targeting of heart failure to potentially aid the management of foot ulcers in diabetes. [ABSTRACT FROM AUTHOR]