Abstract
Background
Hypertension is a prevalent condition that is closely associated with chronic complications
in patients with diabetes. Fixed-dose combination therapy is currently recommended
for the treatment of hypertension due to the advantage of reducing the pill burden.
However, the effects of combination therapy may be diverse because of the different
components.
Objectives
We examined blood pressure reduction and metabolic alterations after amlodipine/benazepril
and valsartan/hydrochlorothiazide treatment in patients with type 2 diabetes mellitus
and hypertension and microalbuminuria.
Methods
This randomized, double-blind, parallel comparison, noninferiority clinical trial
included patients with type 2 diabetes mellitus and hypertension and microalbuminuria
detected within the past year. After a 2-week, placebo run-in period, patients were
assigned to treatment with amlodipine/benazepril or valsartan/hydrochlorothiazide
for 16 weeks. The primary end point was mean change in diastolic blood pressure. The
prespecified boundary for noninferiority was 3.5 mm Hg of the mean change in diastolic
blood pressure between treatments (amlodipine/benazepril minus valsartan/hydrochlorothiazide).
If the upper limit of the 95% CI fell within 3.5 mm Hg, amlodipine/benazepril would
be considered noninferior to valsartan/hydrochlorothiazide.
Results
Of the 226 patients assessed for eligibility, 169 satisfied the inclusion/exclusion
criteria and were assigned to a treatment group; 83 patients (54.2% male, mean age
of 60.5 [10.0] years) in the amlodipine/benazepril group and 84 patients (64.3% male,
mean age of 59.0 [10.6] years) in the valsartan/hydrochlorothiazide group received
at least 1 dose of study medication and were included in the intention-to-treat population.
In the per-protocol population, amlodipine/benazepril (n = 74) was noninferior to
valsartan/hydrochlorothiazide (n = 78) with regard to the mean change in diastolic
blood pressure (difference, −0.9 mm Hg; 95% CI, −3.5 to 1.6). The mean change in systolic
blood pressure was not significantly different (2.4 mm Hg; 95% CI, −1.2 to 6.0) between
study groups (P = 0.195) in the per-protocol population. However, data from the intention-to-treat
population suggest that patients in the amlodipine/benazepril group may have better
metabolic outcomes than those in the valsartan/hydrochlorothiazide group; specifically,
a preservation of the estimated glomerular filtration rate (5.7 mL/min/1.73 m2 [95% CI, 1.9 to 9.6]; P = 0.004) and improvements in glycosylated hemoglobin (−0.5% [95% CI, −0.7 to −0.2];
P < 0.001), fasting triglycerides (−0.4 mmol/L [95% CI, −0.7 to −0.2]; P = 0.002), HDL-C (0.07 mmol/L [95% CI, 0.01 to 0.12]; P = 0.022), and uric acid (−57.5 μmol/L [95% CI, −74.8 to −40.3]; P < 0.001). There were no significant differences in adverse effects between groups,
with the exception of more respiratory disorders in the amlodipine/benazepril group
than in the valsartan/hydrochlorothiazide group (17 vs 5; P = 0 .006).
Conclusions
The study results suggest that amlodipine/benazepril is noninferior to valsartan/hydrochlorothiazide
with regard to blood pressure reduction and that this combination exerts beneficial
effects on renal function, glucose control, HDL-C, and triglyceride levels compared
with valsartan/hydrochlorothiazide. However, respiratory adverse events (particularly
coughing) were more frequently reported in the amlodipine/benazepril group. ClinicalTrials.gov identifier: NCT01375322.
Key words
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Article info
Publication history
Published online: July 12, 2012
Accepted:
June 14,
2012
Identification
Copyright
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
