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.

Autor: Piero Ruggenenti, Monica Cortinovis, Aneliya Parvanova, Matias Trillini, Ilian P Iliev, Antonio C Bossi, Antonio Belviso, Maria C Aparicio, Roberto Trevisan, Stefano Rota, Annalisa Perna, Tobia Peracchi, Nadia Rubis, Davide Martinetti, Silvia Prandini, Flavio Gaspari, Fabiola Carrara, Salvatore De Cosmo, Giancarlo Tonolo, Ruggero Mangili, Giuseppe Remuzzi, VARIETY Study Organization
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: PLoS Medicine, Vol 18, Iss 7, p e1003691 (2021)
Druh dokumentu: article
ISSN: 1549-1277
1549-1676
DOI: 10.1371/journal.pmed.1003691
Popis: BackgroundAngiotensin 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 findingsVARIETY 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.ConclusionsRisk/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 registrationEudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.
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