Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial

Sjølie, Anne Katrin; Klein, Michael L.; Porta, Massimo; Orchard, Trevor J.; Fuller, John; Parving, Hans Henrik; Bilous, Rudy; Chaturvedi, Nish

doi:10.1016/s0140-6736(08)61411-7

Cited by 411 publications

(289 citation statements)

References 45 publications

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“…104 The DIRECT enrolled 1905 individuals with type 2 DM and 3326 individuals with type 1 DM and followed them over a median of approximately 5 years. 105,111 Three outcomes were evaluated in this trial: the development of DR in type 1 DM (DIRECT-Prevent 1), the progression of DR in type 1 (DIRECTProtect 1) and the progression of DR in type 2 DM (DIRECT-Protect 2). The groups did not differ in HbA 1c levels, and treatment with candesartan resulted in a small but significant reduction in blood pressure.…”

Section: Role Of Renin-ang Aldosterone System With Emphasis On Aldostmentioning

confidence: 99%

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

2011

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Diabetes and hypertension frequently coexist and constitute the most notorious combination for the pathogenesis of diabetic nephropathy and retinopathy. Large clinical trials have clearly demonstrated that tight control of glycemia and/or blood pressure significantly reduces the incidence and progression of diabetic retinopathy (DR) and nephropathy. However, the mechanism by which hypertension interacts with diabetes to induce and/or exacerbate nephropathy and retinopathy is very unclear. Substantial evidence implicates the involvement of chronic inflammation and oxidative stress in the pathogenesis of DR and nephropathy. In addition, hypertension causes oxidative stress and inflammation in the kidney and retina. In the present review, we summarized data obtained from our research along with those from other groups to better understand the role of hypertension in the pathogenesis of diabetic nephropathy and retinopathy. It is suggested that oxidative stress and inflammation may be common denominators of kidney and retinal damage in the concomitant presence of diabetes and hypertension.

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Section: Role Of Renin-ang Aldosterone System With Emphasis On Aldostmentioning

confidence: 99%

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

2011

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“…[49] DIRECTProtect 2 assessed the effect of candesartan on progression and regression of retinopathy in type 2 diabetics. [50] D I R E C T -P r e v e n t 1 e n r o l l e d 1 4 2 1 normotensive, normoalbuminuric type 1 diabetic patients (aged 18-50 years) without retinopathy and randomized to candesartan (n = 711) or to placebo (n = 710). DIRECTProtect 1 enrolled 1905 normotensive, normoalbuminuric type 1 diabetic patients (aged 18-55 years) with retinopathy and randomized to candesartan (n = 951) or to placebo (n = 954).…”

Section: T a B L E 1 A M E R I C A N D I A B E T E S A S S O C I A mentioning

confidence: 99%

“…These results showed the beneÞ cial effects of candesartan in improving retinopathy in type 2 diabetic patients. [50] None of the DIRECT trials could achieve the pre-speciÞ ed end points. Further, it must be noted, that the reduction in incidence of retinopathy found in DIRECT Prevent 1 and DIRECT Protect 1 studies or decrease in the progression of retinopathy in DIRECT Protect 2, could not reach traditional statistical significance level, thereby making a clear recommendation of candesartan use for all diabetic patients difficult.…”

Section: T a B L E 1 A M E R I C A N D I A B E T E S A S S O C I A mentioning

confidence: 99%

Diabetic retinopathy: A comprehensive review

Shah¹

2008

Indian J Med Sci

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“…Furthermore, experimental studies indicate that ACE inhibition and type 1 angiotensin receptor blockade (ARB) are protective in models of retinopathy [7][8][9][10][11]. These findings have, to some extent, been translated into clinical trials such as the DIabetic REtinopathy Candesartan Trial (DIRECT), which reported that ARB reduced the incidence of retinopathy in type 1 diabetic patients and increased regression of retinopathy in type 2 diabetic patients [12,13]. ACE inhibition and ARB have also been reported to reduce the progression of diabetic retinopathy in normoalbuminuric and normotensive patients [14].…”

Section: Introductionmentioning

confidence: 99%

Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat

et al. 2011

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Aim/hypothesis We examined whether the renin inhibitor, aliskiren, provides similar or greater protection than ACE inhibition from non-proliferative diabetic retinopathy and from the proliferative neoangiogenesis of oxygen-induced retinopathy. Methods Transgenic (mRen-2)27 rats, which overexpress mouse renin and angiotensin in extra-renal tissues, were studied. For diabetic studies, non-diabetic, diabetic (streptozotocin, 55 mg/kg), diabetic + aliskiren (10 mg kg −1 day −1 , pump), or diabetic + lisinopril (10 mg kg −1 day −1 , drinking water) rats were evaluated over 16 weeks. For oxygeninduced retinopathy studies, rats were exposed to 80% oxygen (22 h/day) from postnatal days 0 to 11, and then room air from postnatal days 12 to 18. Aliskiren (10 or 30 mg kg −1 day −1 , pump) or lisinopril (10 mg kg −1 day −1 , drinking water) was administered during retinopathy development between postnatal days 12 and 18. Results Systolic BP in diabetic (mRen-2)27 rats was reduced with 10 mg kg −1 day −1 aliskiren, but only lisinopril normalised systolic blood pressure. In diabetic (mRen-2)27 rats, 10 mg kg −1 day −1 aliskiren and lisinopril reduced retinal acellular capillaries and leucostasis to non-diabetic levels. In oxygen-induced retinopathy, neoangiogenesis and retinal inflammation (leucostasis, ED-1 immunolabelling) were partially reduced by 10 mg kg −1 day −1 aliskiren and normalised by 30 mg kg −1 day −1 aliskiren, whereas lisinopril normalised neoangiogenesis and reduced leucostasis and ED-1 immunolabelling. Aliskiren and lisinopril normalised retinal vascular endothelial growth factor expression; however, only aliskiren reduced intercellular adhesion molecule-1 to control levels. Conclusions/interpretation Aliskiren provided similar or greater retinal protection than ACE inhibition and may be a potential treatment for diabetic retinopathy.

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Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial

Cited by 411 publications

References 45 publications

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

Diabetic retinopathy: A comprehensive review

Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat

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