In:
PLOS Medicine, Public Library of Science (PLoS), Vol. 18, No. 7 ( 2021-7-14), p. e1003691-
Abstract:
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 .
Type of Medium:
Online Resource
ISSN:
1549-1676
DOI:
10.1371/journal.pmed.1003691
DOI:
10.1371/journal.pmed.1003691.g001
DOI:
10.1371/journal.pmed.1003691.g002
DOI:
10.1371/journal.pmed.1003691.g003
DOI:
10.1371/journal.pmed.1003691.g004
DOI:
10.1371/journal.pmed.1003691.t001
DOI:
10.1371/journal.pmed.1003691.t002
DOI:
10.1371/journal.pmed.1003691.s001
DOI:
10.1371/journal.pmed.1003691.s002
DOI:
10.1371/journal.pmed.1003691.s003
DOI:
10.1371/journal.pmed.1003691.s004
DOI:
10.1371/journal.pmed.1003691.s005
DOI:
10.1371/journal.pmed.1003691.s006
DOI:
10.1371/journal.pmed.1003691.s007
DOI:
10.1371/journal.pmed.1003691.s008
DOI:
10.1371/journal.pmed.1003691.s009
DOI:
10.1371/journal.pmed.1003691.s010
DOI:
10.1371/journal.pmed.1003691.s011
DOI:
10.1371/journal.pmed.1003691.s012
DOI:
10.1371/journal.pmed.1003691.r001
DOI:
10.1371/journal.pmed.1003691.r002
DOI:
10.1371/journal.pmed.1003691.r003
DOI:
10.1371/journal.pmed.1003691.r004
DOI:
10.1371/journal.pmed.1003691.r005
DOI:
10.1371/journal.pmed.1003691.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2164823-2
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