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A.K. Sjolie, Diabetic Retinopathy Candesartan Trials ProgrammeStudy Group; Baseline Data From the Diabetic Retinopathy Candesartan Trials Programme . Invest. Ophthalmol. Vis. Sci. 2005;46(13):387.
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Purpose: To examine the incidence(primary prevention) and progression (secondary prevention) of diabetic retinopathy when blocking the angiotensin II type 1–receptors in normoalbuminuric, normotensive Type 1 and normoalbuminuric, normotensive or treated hypertensive Type 2 diabetic patients. Methods:Standardised investigations at enrolment included blood pressure measurement, HbA1c and serum lipids. Retinopathy was assessed yearly using seven–field stereo photographs according to ETDRS protocol, and graded centrally. At randomisation, treatment with 16 mg candesartan or matching placebo was initiated, and increased to 32 mg after one month. A sample size assessment was originally carried out using observational studies and clinical trials. A sample size re–assessment was carried out when approximately 70% of the patients had been randomised. Results: 5231 patients were randomised globally,1421 and 1905 patients in the primary and secondary prevention studies in Type 1 patients, respectively and 1905 patients in the secondary prevention study in Type 2. HbA1c showed mean values of 8.1, 8.5 and 8.2% for the3 studies, respectively with no significant regional differences. In the Type 1 secondary prevention study 49% of the patients had level 20 in at least one eye, and 9% had level 43–47. In Type 2 patients, 17% had level 43–47 and the remainder less severe retinopathy. Significant correlation with retinopathy levels at baseline was found with duration of diabetes (p<0.0001), HbA1c (p<0.0001), and systolic blood pressure (p=0.003) in both Type 1 and Type 2 patients. Diastolic blood pressure was significantly correlated with retinopathy level in Type 1 patients (p=0.001). Discussion: RAS blockade has been shown superior to other antihypertensive therapy in slowing progression of renal disease in diabetic patients. Still questions remain regarding diabetic retinopathy. Experimental evidence indicates that total blockade of the RAS system is necessary for an optimal organ protective effect, hence a maximum dose of candesartan cilexetil of 32 mg is being used in the DIRECT Programme. Two– or 3–step changes on the ETDRS scale are good predictors of visual loss and are accepted by regulatory agencies as a valid surrogate for blindness. By utilising actual baseline data collected in the DIRECT Programme we were able to adjust the statistical power calculations, which was considered necessary for the possibility for the DIRECT Programme to be conclusive. Conclusions: Pharmacological interventions may have important implications for the future care of diabetic patients.
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