Treatment with candesartan can increase regression of retinopathy in type 2 diabetes and reduce incidence of retinopathy in type 1 diabetes. These are among the conclusions of the DIRECT studies, published early Online and in an upcoming edition of The Lancet.
Diabetic retinopathy is a leading cause of blindness in people of working age. In the first of the two Articles, Professor Nish Chaturvedi, National Heart and Lung Institute, Imperial College Healthcare NHS Trust, London, UK, and colleagues, examine the effect of candesartan on incidence and progression of retinopathy in type 1 diabetes. Two randomised controlled trials formed this part of the study - DIRECT-Prevent 1 for patients without existing retinopathy and DIRECT-Protect 1 for patients already with the condition. In DIRECT-Prevent 1, 711 patients received candesartan and 710 placebo; and the researchers found that the incidence of retinopathy was 18% lower for patients given candersartan, a result with borderline statistical significance. In DIRECT-Protect 1, 951 patients received candesartan and 954 placebo, with no statistically significant difference overall in retinopathy progression between the two groups. However, further analysis revealed that risk of retinopathy progression by three or more steps on the EDTRS scale* was 35% lower for candesartan patients compared with placebo. And a patient's final 'stage' of retinopathy after the four-year long trial was more likely to have improved with candesartan compared with placebo in both DIRECT-Prevent 1 (by 16%) and in DIRECT-Protect 1 (by 12%). The authors conclude: "Although candesartan reduces the incidence of retinopathy, we did not see a beneficial effect on retinopathy progression."
In the second Article, Professor Anne Sjølie, Odense University Hospital, Denmark, and colleagues, report the DIRECT-Protect 2 study — a randomised controlled trial to analyse the effect of candesartan on both slowing progression and inducing regression of retinopathy in patients with type 2 diabetes. The trial looked at 1905 patients with mild to moderately severe retinopathy, 951 received candesartan 16mg once per day (doubled to 32mg after one month) and 954 placebo. The researchers found that 17% of candesartan patients and 19% on placebo had progression of retinopathy by three or more steps on the ETDRS scale - a non-statistically significant risk reduction of 13% for candesartan patients. Regression (defined as a 3-step improvement or a persistent 2-step improvement confirmed in 2 consecutive visits on the ETDRS scale) was increased by 34% in the candesartan group compared with placebo. Finally, patients in the candesartan group were 17% more likely than placebo to experience an overall change towards less severe retinopathy by the end of the trial. The authors conclude: "These results suggest that treatment with candesartan in type 2 diabetic patients with mild to moderate retinopathy could induce improvement of retinopathy."
In an accompanying Comment, Dr Paul Mitchell, Centre for Vision Research, University of Sydney, Australia, and Dr Tien Y Wong, Centre for Eye Research Australia, University of Melbourne, Australia, and Singapore National University, say: "Clearly, prevention of retinopathy development and progression, or induction of its regression, could have widespread benefits both on the eye and the systemic health of people with diabetes. The DIRECT trials' conclusions that candesartan reduces retinopathy development in type 1 diabetes and benefits its evolution in type 2 are therefore justified, with some caveats."
Professor Nish Chaturvedi, , National Heart and Lung Institute, Imperial College Healthcare NHS Trust, London, UK T) + 44 (0) 207 594 3381 E) n.chaturvedi@imperial.ac.uk
Professor Anne Sjølie, Odense University Hospital, Denmark, T) +45 6541 2782 A.K.Sjoelie@ouh.regionsyddanmark.dk
Dr Paul Mitchell, Centre for Vision Research, University of Sydney, Australia T) +61 2 9845 7953 / +61 408 058 199 E) paul_mitchell@wmi.usyd.edu.au
Notes to editors: *EDTRS = Early Treatment Diabetic Retinopathy Study scale, the gold standard for determining progression in diabetic retinopathy
Full Article and Comment: http://press.thelancet.com/directfinal.pdf
Journal
The Lancet