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Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monothe...

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Autores principales: Ruggenenti, Piero, Cortinovis, Monica, Parvanova, Aneliya, Trillini, Matias, Iliev, Ilian P., Bossi, Antonio C., Belviso, Antonio, Aparicio, Maria C., Trevisan, Roberto, Rota, Stefano, Perna, Annalisa, Peracchi, Tobia, Rubis, Nadia, Martinetti, Davide, Prandini, Silvia, Gaspari, Flavio, Carrara, Fabiola, De Cosmo, Salvatore, Tonolo, Giancarlo, Mangili, Ruggero, Remuzzi, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279302/
https://www.ncbi.nlm.nih.gov/pubmed/34260595
http://dx.doi.org/10.1371/journal.pmed.1003691
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author Ruggenenti, Piero
Cortinovis, Monica
Parvanova, Aneliya
Trillini, Matias
Iliev, Ilian P.
Bossi, Antonio C.
Belviso, Antonio
Aparicio, Maria C.
Trevisan, Roberto
Rota, Stefano
Perna, Annalisa
Peracchi, Tobia
Rubis, Nadia
Martinetti, Davide
Prandini, Silvia
Gaspari, Flavio
Carrara, Fabiola
De Cosmo, Salvatore
Tonolo, Giancarlo
Mangili, Ruggero
Remuzzi, Giuseppe
author_facet Ruggenenti, Piero
Cortinovis, Monica
Parvanova, Aneliya
Trillini, Matias
Iliev, Ilian P.
Bossi, Antonio C.
Belviso, Antonio
Aparicio, Maria C.
Trevisan, Roberto
Rota, Stefano
Perna, Annalisa
Peracchi, Tobia
Rubis, Nadia
Martinetti, Davide
Prandini, Silvia
Gaspari, Flavio
Carrara, Fabiola
De Cosmo, Salvatore
Tonolo, Giancarlo
Mangili, Ruggero
Remuzzi, Giuseppe
author_sort Ruggenenti, Piero
collection PubMed
description BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. METHODS AND FINDINGS: VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. CONCLUSIONS: Risk/benefit profile of study treatments was similar. Dual renin–angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients. TRIAL REGISTRATION: EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.
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spelling pubmed-82793022021-07-31 Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study Ruggenenti, Piero Cortinovis, Monica Parvanova, Aneliya Trillini, Matias Iliev, Ilian P. Bossi, Antonio C. Belviso, Antonio Aparicio, Maria C. Trevisan, Roberto Rota, Stefano Perna, Annalisa Peracchi, Tobia Rubis, Nadia Martinetti, Davide Prandini, Silvia Gaspari, Flavio Carrara, Fabiola De Cosmo, Salvatore Tonolo, Giancarlo Mangili, Ruggero Remuzzi, Giuseppe PLoS Med Research Article BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. METHODS AND FINDINGS: VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. CONCLUSIONS: Risk/benefit profile of study treatments was similar. Dual renin–angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients. TRIAL REGISTRATION: EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152. Public Library of Science 2021-07-14 /pmc/articles/PMC8279302/ /pubmed/34260595 http://dx.doi.org/10.1371/journal.pmed.1003691 Text en © 2021 Ruggenenti et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ruggenenti, Piero
Cortinovis, Monica
Parvanova, Aneliya
Trillini, Matias
Iliev, Ilian P.
Bossi, Antonio C.
Belviso, Antonio
Aparicio, Maria C.
Trevisan, Roberto
Rota, Stefano
Perna, Annalisa
Peracchi, Tobia
Rubis, Nadia
Martinetti, Davide
Prandini, Silvia
Gaspari, Flavio
Carrara, Fabiola
De Cosmo, Salvatore
Tonolo, Giancarlo
Mangili, Ruggero
Remuzzi, Giuseppe
Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study
title Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study
title_full Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study
title_fullStr Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study
title_full_unstemmed Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study
title_short Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study
title_sort preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: a prospective, randomized, open-label, blinded endpoint (probe) study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279302/
https://www.ncbi.nlm.nih.gov/pubmed/34260595
http://dx.doi.org/10.1371/journal.pmed.1003691
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