Comparison of the Efficacy and Safety Profiles of Two Fixed-Dose Combinations of Antihypertensive Agents, Amlodipine/Benazepril Versus Valsartan/Hydrochlorothiazide, in Patients With Type 2 Diabetes Mellitus and Hypertension: A 16-Week, Multicenter, Randomized, Double-Blind, Noninferiority Study
Journal
Clinical Therapeutics
Journal Volume
34
Journal Issue
8
Pages
1735-1750
Date Issued
2012
Author(s)
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. ? 2012 Elsevier HS Journals, Inc.
SDGs
Other Subjects
alanine aminotransferase; amlodipine plus benazepril; amtrel; aspartate aminotransferase; cholesterol; creatinine; glucose; hemoglobin A1c; high density lipoprotein cholesterol; hydrochlorothiazide plus valsartan; low density lipoprotein cholesterol; nifedipine; placebo; potassium; sodium; triacylglycerol; unclassified drug; uric acid; adult; alanine aminotransferase blood level; antihypertensive therapy; article; aspartate aminotransferase blood level; blood glucose monitoring; blood pressure measurement; cholesterol blood level; controlled study; coughing; creatinine blood level; diabetic hypertension; diastolic blood pressure; dizziness; double blind procedure; drug efficacy; drug fatality; drug safety; drug withdrawal; duodenal ulcer bleeding; falling; female; flushing; gastrointestinal symptom; glomerulus filtration rate; glucose blood level; hemoglobin blood level; human; hyperkalemia; hypertension; hypotension; infection; kidney function; major clinical study; male; microalbuminuria; multicenter study; musculoskeletal disease; neurologic disease; non insulin dependent diabetes mellitus; nutritional disorder; outcome assessment; parallel design; patient compliance; peptic ulcer; potassium blood level; prospective study; radius fracture; randomized controlled trial; respiratory tract disease; side effect; sodium blood level; sore throat; systolic blood pressure; thrombocytopenia; treatment duration; triacylglycerol blood level; uric acid blood level; Aged; Albuminuria; Amlodipine; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Biological Markers; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diuretics; Double-Blind Method; Drug Combinations; Female; Hemoglobin A, Glycosylated; Humans; Hydrochlorothiazide; Hypertension; Lipids; Male; Middle Aged; Prospective Studies; Taiwan; Tetrazoles; Time Factors; Treatment Outcome; Uric Acid; Valine
Type
journal article