Summary
Candesartan may have a place in the treatment of retinopathy in patients with type 1 or 2 diabetes, according to findings from the Diabetic Retinopathy Candesartan Trials (DIRECT) study program. The DIRECT-Protect 1 and 2 trials are the first to show the potential benefits of angiotensin-II receptor blockers in patients with baseline diabetic retinopathy.
- endocrinology
- retinal diseases
Candesartan may have a place in the treatment of retinopathy in patients with type 1 or 2 diabetes, according to findings from the Diabetic Retinopathy Candesartan Trials (DIRECT) study program. The DIRECT-Protect 1 and 2 trials are the first to show the potential benefits of angiotensin-II receptor blockers (ARBs) in patients with baseline diabetic retinopathy (Figure 1).
DIRECT-Protect 1 and 2 examined the effect of candesartan on the progression of retinopathy in patients with type 1 or 2 diabetes, respectively. Nishi Chaturvedi, MD, Imperial College London, UK, presented the findings from DIRECT-Protect 1 and was followed by Anne Katrin Sjølie, MD, Odense University Hospital, Denmark, who presented the findings from DIRECT-Protect 2.
No Benefits in Type 1 Diabetes
The DIRECT-Protect 1 trial included 1905 patients with type 1 diabetes and evidence of retinopathy, which was defined as ≥20/10 up to ≤47/47 on the Early Treatment of Diabetic Retinopathy Study [ETDRS] scale. At baseline, all patients had normal blood pressure (≤130/85 mm Hg) and normal albumin levels. The mean age was 32 years, and the mean duration of disease was 11 years.
Patients were randomly assigned to treatment with candesartan (n=951) or placebo (n=954) for at least 4 years. The primary endpoint was progression of retinopathy (measured by 3-step change on the 11-point ETDR Scale). By the end of the trial, candesartan appeared to have no effect on retinopathy progression (HR=1.02; p=0.8; Figure 2).
Among patients with type 1 diabetes, the most common adverse events (AEs) were nasopharyngitis, hypoglycemia, hypotension, and headache. A similar proportion of patients in the candesartan and placebo groups experienced any AE (77.6% vs 75.8%) or discontinued study medication due to AEs (1.8% vs 1.7%).
Reversal of Retinopathy in Type 2 Diabetes
In the DIRECT-Protect 2 trial, 1905 patients with type 2 diabetes and retinopathy were randomly assigned to treatment with candesartan (n=951) or placebo (n=954). At baseline, 62% of patients had elevated blood pressure (>130/85 mm Hg) and required antihypertensive treatment with an agent other than a RAS inhibitor.
Treatment with candesartan was associated with a nonsignificant 13% reduction in the progression of retinopathy (p=0.2). Therefore, DIRECT-Protect 2 failed to meet its primary endpoint. However, candesartan excelled in a secondary endpoint: regression of retinopathy. Patients in the candesartan group were 34% more likely to experience retinopathy regression (p=0.009) when adjusted for baseline level of retinopathy, diabetes duration, HbA1c level, urinary albumin excretion rate, antihypertensive treatment, and systolic blood pressure during the study (Figure 3). A similar proportion of patients in the candesartan and placebo groups experienced any AE (83.9% vs 82.5%) or discontinued study medication due to AEs (3.9% vs 4.4%).
“Diabetic retinopathy is one of the most feared and common complications of diabetes, making this an important clinical finding,” Prof. Sjølie said. “The reversal of this vision-threatening complication of diabetes has not been reported before in large-scale clinical trials.”
- © 2008 MD Conference Express