The DIabetic REtinopathy Candesartan Trials (DIRECT) Programme: baseline characteristics

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Abstract
Renin-angiotensin system blockade has been shown to be superior to other antihypertensive therapy in slowing progression of renal disease in diabetic patients, but questions remain regarding diabetic retinopathy. The primary objective of the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme is to examine primary (incidence) and secondary (progression) prevention of diabetic retinopathy when blocking angiotensin II type 1-receptors with candesartan in normoalbuminuric, normotensive Type 1 diabetic patients, and secondary prevention only in normoalbuminuric, normotensive or treated hypertensive Type 2 diabetic patients. The secondary objectives include examining the effect of candesartan treatment on urinary albumin excretion rate (UAER) in each of the three studies and to examine the incidence of proliferative retinopathy in all three populations combined. Standardised investigations for patients at enrolment include blood pressure measurement analysis of HbA1C and serum lipids, and a detailed ophthalmological examination. Retinopathy and UAER outcomes are assessed yearly. Retinopathy is graded centrally, based on seven-field stereo photographs using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Randomisation was performed when the results of retinal gradings were available, and treatment with 16 mg candesartan cilexetil or matching placebo was initiated; the dose was increased to 32 mg after one month. Calculations of UAER are based on two timed overnight urine collections. A sample size re-assessment was carried out when approximately 70% of the patients had been randomised in the DIRECT Programme to ensure the results to be conclusive. In total, 5,231 patients were randomised in the DIRECT Programme in 30 countries. One thousand, four hundred and twenty one and 1,905 patients are evaluated in the primary and secondary prevention studies in Type 1 diabetes, respectively and 1,905 patients in the secondary prevention study in Type 2 diabetes. HbA1C showed mean values of 8.1, 8.5 and 8.2% for the Type 1 primary, Type 1 secondary and Type 2 secondary prevention studies, respectively. In the Type 1 secondary prevention study, 49% of the patients had mild nonproliferative retinopathy (level 20) in at least one eye, and 9% had moderate-moderately severe non-proliferative retinopathy (level 43—47). In Type 2 patients, 17% had level 43—47 and the remainder less severe retinopathy.