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The Effect of the Angiotensin Receptor Blocker Candesartan on Regression of Retinopathy in Type 2 Diabetes

¹Ophthalmology, Odense University Hospital, Odense, Denmark
²Ophthalmology and Visual Science, University of Wisconsin, Madison, Odense, Wisconsin
³Intern. Centre for Circulatory Health, Imperial College HealthcareNHS Trust, London, United Kingdom
⁴Dept. of Internal Medicine, University of Turin, Turin, Italy
⁵Dept. of Epidemiology and Public Health, University College London, London, United Kingdom
⁶Dept. of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
⁷Dept. of Medical Endocrinology, South Cleveland Hospital, Middlesbrough, United Kingdom
⁸Dept. of Medical Endocrinology, University Hospital Copenhagen, Copenhagen, Denmark

Commercial Relationships: A.K. Sjolie, Astrazeneca and Takeda, R; R. Klein, AstraZeneca and Takeda, R; N. Chaturvedi, AstraZeneca and Takeda, R; M. Porta, AstraZeneca and Takeda, R; J. Fuller, AstraZeneca and Takeda, R; T. Orchard, AstraZeneca and Takeda, R; R. Bilous, AstraZeneca and Takeda, R; H.-H. Parving, AstraZeneca and Takeda, R.

Support: None.

Clinical Trial: www.clinicaltrials.gov NCT00252694

Abstract

Purpose:DIRECT-Protect 2 was designed to examine whether candesartan treatment could slow progression and induce regression of retinopathy in people with type 2 diabetes. We here report the results on regression of retinopathy with particular focus on blood pressure and other baseline risk factors.

Methods:DIRECT-Protect 2 was a randomised, double-blind, parallel-design, placebo-controlled trial in 309 centres globally, recruiting normoalbuminuric, normotensive (BP130/85) or treated hypertensive (BP160/90) people with type 2 diabetes with mild to moderately severe retinopathy (ETDRS levels 20-47). Retinopathy was assessed using the ETDRS severity scale. Photographs were taken at baseline and annually for at least 4 years. Regression was defined as a reduction by at least 3 or more steps of retinopathy on the ETDRS scale from baseline to any one follow-up visit, or 2 or more steps sustained at two consecutive follow-up visits.

Results:1905 participants were randomised. Regression on active treatment was significantly increased by 34% (HR 1·34, 95% CI 1·08-1·68, p=0·009). When analysing regression of retinopathy by hypertension treatment, the effect of treatment with candesartan appeared similar in patients with normal blood pressure at baseline compared to those on treatment for hypertension (p-value for heterogeneity=0.86). Hazard ratios and p-values in normotensive and hypertensive patients were 1.49 (p=0.035) and 1.27 (p=0.094), respectively. Subgroup analyses according to baseline retinopathy levels showed that regression was induced in eyes with level 35 on the ETDRS scale, whereas there was no effect in eyes with more severe retinopathy. The effect of candesartan on regression of retinopathy was consistent across subgroups based on baseline HbA1c, UAER and waist-hip ratio.

Conclusions:Treatment with candesartan in type 2 diabetic patients with mild to moderate retinopathy induced significant improvement in retinopathy over 4 years irrespective of hypertension status at baseline.

Keywords: diabetes • retina • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials

© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.