Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Chaturvedi, N; Porta, M; Klein, R; Orchard, T; Fuller, J; Parving, HH; Bilous, R; Sjølie, AK; DIRECT Programme Study Group.
Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials.
Lancet. 2008; 372(9647):1394-1402 Doi: 10.1016/S0140-6736(08)61412-9
Web of Science PubMed FullText FullText_MUG

Study Group Members Med Uni Graz:: Pilger Ernst
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: Background Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression of retinopathy in type 1 diabetes. Methods Two randomised, double-blind, parallel-design, placebo-controlled trials were done in 309 centres worldwide. Participants with normotensive, normoalbuminuric type 1 diabetes without retinopathy were recruited to the DIRECT-Prevent I trial and those with existing retinopathy were recruited to DIRECT-Protect 1, and were assigned to candesartan 16 mg once a day or matching placebo. After I month, the dose was doubled to 32 mg. Investigators and participants were unaware of the treatment allocation status. The primary endpoints were incidence and progression of retinopathy and were defined as at least a two-step and at least a three-step increase on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, respectively. These trials are registered with ClinicalTrials.gov, numbers NCT00252733 for DIRECT-Prevent 1 and NCT00252720 for DIRECT-Protect 1. Findings 1421 participants (aged 18-50 years) were randomly assigned to candesartan (n=711) or to placebo (n=710) in DIRECT-Prevent 1, and 1905 (aged 18-55 years) to candesartan (n=951) or to placebo (n=954) in DIRECT-Protect 1. Incidence of retinopathy was seen in 178 (25%) participants in the candesartan group versus 217 (31%) in the placebo group. Progression of retinopathy occurred in 127 (13%) participants in the candesartan group versus 124 (13%) in the placebo group. Hazard ratio (HR for candesartan vs placebo) was 0.82 (95% CI 0.67-1.00, p=0.0508) for incidence of retinopathy and 1.02 (0.80-1.31, p=0.85) for progression of retinopathy. The post-hoc outcome of at least a three-step increase for incidence yielded an HR of 0.65 (0.48-0.87, p=0.0034), which was attenuated but still significant after adjustment for baseline characteristics (0.71, 0.53-0.95, p=0.046). Final ETDRS level was more likely to have improved with candesartan treatment in both DIRECT-Prevent 1 (odds 1.16, 95% CI 1.05-1.30, p=0.0048) and DIRECT-Protect 1 (1.12, 95% CI 1.01-1.25, p=0.0264). Adverse events did not differ between the treatment groups. Interpretation Although candesartan reduces the incidence of retinopathy, we did not see a beneficial effect on retinopathy progression.
Find related publications in this database (using NLM MeSH Indexing): Adolescent -; Adult -; Angiotensin II Type 1 Receptor Blockers - adverse effects Angiotensin II Type 1 Receptor Blockers - therapeutic use; Benzimidazoles - adverse effects Benzimidazoles - therapeutic use; Diabetes Mellitus, Type 1 - complications Diabetes Mellitus, Type 1 - drug therapy; Diabetic Retinopathy - classification Diabetic Retinopathy - drug therapy Diabetic Retinopathy - etiology; Double-Blind Method -; Female -; Humans -; Hypoglycemic Agents - therapeutic use; Insulin - therapeutic use; Male -; Middle Aged -; Severity of Illness Index -; Tetrazoles - adverse effects Tetrazoles - therapeutic use; Treatment Outcome -