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dc.contributor.authorChaturvedi, Nish
dc.contributor.authorPorta, Massimo
dc.contributor.authorKlein, Ronald
dc.contributor.authorOrchard, Trevor
dc.contributor.authorFuller, John
dc.contributor.authorParving, Hans-Henrik
dc.contributor.authorBilous, Rudy
dc.contributor.authorSjolie, Anne Katrin
dc.contributor.authorFox, Ywonne
dc.contributor.authorGeorge, Michael
dc.contributor.authorSvensson, Anders
dc.contributor.authorHainer, James
dc.contributor.authorWarnold, Ingrid
dc.contributor.authorAgardh, Carl-David
dc.contributor.authorBonnici, Francois
dc.contributor.authorCharbonnel, Bernard
dc.contributor.authorCooper, Mark
dc.contributor.authorDedov, Ivan
dc.contributor.authorGardiner, Robert
dc.contributor.authorGomis, Ramon
dc.contributor.authorIlkova, Hasan
dc.contributor.authorKatsilambros, Nicholas
dc.contributor.authorKerenyi, Zsuzsa
dc.contributor.authorMartin, Stephan
dc.contributor.authorMassin, Pascale
dc.contributor.authorPirags, Valdis
dc.contributor.authorRaz, Itamar
dc.contributor.authorRusavy, Zdenek
dc.contributor.authorSchernthaner, Guntram
dc.contributor.authorShestakova, Marina
dc.contributor.authorStrojek, Krzysztof
dc.contributor.authorOlofsson, Bertil
dc.contributor.authorMalm, Anders
dc.contributor.authorWissmar, Jenny
dc.contributor.authorBrayshaw, Nigel
dc.contributor.authorWedel, Hans
dc.contributor.authorWilhelmsen, Lars
dc.contributor.authorBird, Alan
dc.contributor.authorPrice, Graham
dc.contributor.authorAdler-Ekholm, Elisabeth
dc.contributor.authorAldington, Stephen
dc.contributor.authorDahl, Magnus
dc.contributor.authorDeveney, Aaron
dc.contributor.authorKarlsten, Eva
dc.contributor.authorLevins, Philippa
dc.contributor.authorLipinski, Helen
dc.contributor.authorPrenter, Carol
dc.contributor.authorWalkey, Helen
dc.contributor.authorWalters, Nicola
dc.contributor.authorChen, Roger
dc.contributor.authorColman, Peter
dc.contributor.authorDavoren, Peter
dc.contributor.authorDonelly, Thomas
dc.contributor.authoret al.
dc.date.accessioned2017-05-03T15:27:37Z
dc.date.available2017-05-03T15:27:37Z
dc.date.issued2008
dc.identifier.issn01406736
dc.identifier.doi10.1016/S0140-6736(08)61412-9
dc.identifier.urihttp://hdl.handle.net/10072/26241
dc.description.abstractBackground: 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 1 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 1 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縲 (95% CI 0綷-1簰, p=0簵08) for incidence of retinopathy and 1簲 (0縰-1糱, p=0縵) for progression of retinopathy. The post-hoc outcome of at least a three-step increase for incidence yielded an HR of 0綵 (0紸-0縷, p=0簰34), which was attenuated but still significant after adjustment for baseline characteristics (0緱, 0絳-0繵, p=0簴6). Final ETDRS level was more likely to have improved with candesartan treatment in both DIRECT-Prevent 1 (odds 1籶, 95% CI 1簵-1糰, p=0簰48) and DIRECT-Protect 1 (1籲, 95% CI 1簱-1粵, p=0簲64). 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. Funding: AstraZeneca and Takeda.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoen_US
dc.publisherThe Lancet Publishing Group
dc.publisher.placeUnited Kingdom
dc.publisher.urihttp://www.thelancet.com/
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1394
dc.relation.ispartofpageto1402
dc.relation.ispartofjournalLancet
dc.relation.ispartofvolume372
dc.rights.retentionY
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode11
dc.titleEffect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2014-10-10T01:56:17Z
gro.hasfulltextNo Full Text
gro.griffith.authorDavoren, Peter M.


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