Hypertension, Diabetes Mellitus
Conditions
Keywords
Hypertension, Diabetes Mellitus, Vascular stiffness, Endothelial function
Brief summary
The purpose of this study is to compare losartan and benazepril in diabetic patients whose high blood pressure is not controlled by amlodipine and its relationship to statin current use.
Detailed description
Hypertension and diabetes mellitus are important risk factors for cardiovascular morbidity and mortality. Endothelial dysfunction and vascular rigidity are two pathophysiological mechanisms that may explain this relationship. Recent publications showed that both ACEi (angiotensin-converting enzyme inhibitor-induced) and ARB (angiotensin receptor blocker) were capable of improving vascular stiffness and endothelial function, and that these effects occurred despite blood pressure reduction. This study main objective is to assess if ARB (losartan) effects are different from ACEi (benazepril) in endothelial function in patients with diabetes mellitus type 2 and blood pressure not controlled by amlodipine and its relationship to statin current use. Secondary analysis of vascular stiffness will be measured by pulse wave velocity and augmentation index. Echocardiographic parameters, such as indexes of diastolic function, will also be measured.
Interventions
DRUGBenazepril
Patients in this group will receive 20 mg of benazepril per day, orally, during 12 weeks.
DRUGLosartan
Patients in this group will receive 100 mg of losartan per day, orally, during 12 weeks.
Sponsors
Hospital Universitario Pedro Ernesto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Ambulatorial patients with age between 40 and 70 years-old. * Systemic arterial hypertension previously diagnosed and in use of two or less anti-hypertensive drugs in the preceding 4 weeks. * Type 2 diabetes mellitus in use of oral medication that were not changed in the preceding 4 weeks. Glycated hemoglobin A1c less than 9.0%. * Accepted the consent form.
Exclusion criteria
* Office systolic blood pressure equal or more than 180 mmHg, with or without treatment * Office diastolic blood pressure equal or more than 110 mmHg, with or without treatment * Evidences of a secondary cause for hypertension * Glycated hemoglobin A1c \> 9.0% * Insulin therapy * Chronic kidney disease stage 4 or 5 or in dialysis * Advanced target organ lesion, obtained by history or additional exams, and defined by: previous myocardial infarction, heart failure with ejection fraction less than 40%, cerebral vascular accident (ischemic or hemorrhagic), peripheral vascular disease (claudication or doppler with obstruction \> 50% of vascular lumen), retinopathy with visual loss, symptomatic neuropathy. * Cardiac arrhythmias, except for ectopic beats * Any clinical or disabling condition that, in the opinion of the investigators, may confound or prejudice study results. * Severe mitral regurgitation. * Women in fertile age without contraceptive methods in use. * Breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial Function | 12 weeks | Access endothelial function by brachial flow-mediated vasodilation (FMD) and compare it between groups (losartan and benazepril) and its relationship to current statin use. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vascular Stiffness | 12 weeks. | Access vascular stiffness by pulse wave velocity and compare it between groups (losartan and benazepril). |
| Systolic Blood Pressure | 12 weeks | Compare both groups effects on systolic blood pressure. |
| Diastolic Blood Pressure | 12 weeks | Compare both group effects on diastolic blood pressure. |
| Vascular Stiffness by Augmentation Index | 12 weeks | Estimate vascular stiffness by measuring augmentation index and compare it between losartan and benazepril groups. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Losartan This group will receive 100 mg of losartan per day. Amlodipine will be maintained.
Losartan: Patients in this group will receive 100 mg of losartan per day, orally, during 12 weeks. | 16 |
| Benazepril This group will receive 20 mg of benazepril per day. Amlodipine will be maintained.
Benazepril: Patients in this group will receive 20 mg of benazepril per day, orally, during 12 weeks. | 14 |
| Total | 30 |
Baseline characteristics
| Characteristic | Losartan | Benazepril | Total |
|---|---|---|---|
| Age, Continuous | 57 years | 57 years | 57 years |
| Region of Enrollment Brazil | 16 participants | 14 participants | 30 participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 16 | 1 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 |
Outcome results
Primary
Endothelial Function
Access endothelial function by brachial flow-mediated vasodilation (FMD) and compare it between groups (losartan and benazepril) and its relationship to current statin use.
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Losartan | Endothelial Function | 9.4 percentage of maximal vasodilation |
| Benazepril | Endothelial Function | 8.8 percentage of maximal vasodilation |
p-value: 0.616Wilcoxon (Mann-Whitney)
Secondary
Diastolic Blood Pressure
Compare both group effects on diastolic blood pressure.
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Losartan | Diastolic Blood Pressure | 80 mmHg |
| Benazepril | Diastolic Blood Pressure | 82 mmHg |
Secondary
Systolic Blood Pressure
Compare both groups effects on systolic blood pressure.
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Losartan | Systolic Blood Pressure | 134 mmHg |
| Benazepril | Systolic Blood Pressure | 139 mmHg |
p-value: 0.618Wilcoxon (Mann-Whitney)
Secondary
Vascular Stiffness
Access vascular stiffness by pulse wave velocity and compare it between groups (losartan and benazepril).
Time frame: 12 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Losartan | Vascular Stiffness | 8.5 m/s |
| Benazepril | Vascular Stiffness | 8.5 m/s |
p-value: 0.28Wilcoxon (Mann-Whitney)
Secondary
Vascular Stiffness by Augmentation Index
Estimate vascular stiffness by measuring augmentation index and compare it between losartan and benazepril groups.
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Losartan | Vascular Stiffness by Augmentation Index | 28 percentage of augmentation pressure |
| Benazepril | Vascular Stiffness by Augmentation Index | 35 percentage of augmentation pressure |