Hypertension
Conditions
Keywords
Bisoprolol, Atenolol, Hypertension, Blood pressure
Brief summary
Antihypertensive drugs aim to reduce blood pressure (BP) either through decrease of the total peripheral resistance through vasodilatation at the level of arterioles (microcirculation) or by decreasing the cardiac output through reduction of the stroke volume or heart rate or both. On the other hand, all antihypertensive drugs might potentially decrease arterial stiffness passively with the reduction of the distending pressure or with the resynchronization of the reflected pressure wave. With theses potential mechanisms, it is also expected that these drugs might exert a favorable effect on pulse pressure amplification between central and peripheral arteries. However, there is solid evidence that the widely applied antihypertensive drugs have differential effect on brachial and central BP. Several reports in the past have confirmed the potential hypothesis that beta blockers decrease central BP less than the observed reduction at the level of the brachial artery. It has been hypothesized that deceleration of heart rate and the re synchronizing the reflected pressure wave earlier in the systolic phase seems to be the leading cause of non-favorable effect of beta blockers on central BP, these effects might be partially counterbalanced in beta blockers with high beta-1 selectivity resulting in less peripheral vasoconstriction properties.
Detailed description
Central pulse pressure is a better predictor of left ventricular mass and carotid intima thickness, and the conventional peripheral BP does not seem to be an accurate reflection of central arterial BP. The pulse pressure amplification between peripheral and central arteries reflects the left ventricular afterload, subendothelial viability, and the intensity of cyclic stress imposed to the renal and cerebral micro- and macro vessels. As central hemodynamic parameters are independently associated with organ damage and are closely related to important cardiovascular outcome, it is suggested that the new clinical trials on antihypertensive drug treatment should compare simultaneously the chronic effect of drugs on both peripheral and central BP. OBJECTIVES Primary objective: * To assess the effect of bisoprolol versus atenolol on the aortic pulse pressure as a central hemodynamic index in subjects with hypertension Secondary objectives: * To assess the effect of bisoprolol versus atenolol on the aortic BP as a central hemodynamic index in subjects with hypertension * To assess the effect of bisoprolol versus atenolol on the AIx and cfPWV as arterial stiffness indexes in subjects with hypertension * To assess the effect of bisoprolol versus atenolol on the aortic pulse pressure as a central hemodynamic index at interim visit (Visit 4) * To assess the effect of bisoprolol versus atenolol on the lipid profile and serum glucose as metabolism indexes * To assess the effect of bisoprolol versus atenolol on the brachial BP as a peripheral BP index in subjects with hypertension * To assess the safety and tolerability of bisoprolol versus atenolol in subjects with hypertension The present study will be approximately of 14 weeks duration comprising of 1 week screening, followed by a 12 weeks treatment period and a 2 weeks post study follow up contact conducted via telephone to monitor additional serious adverse experiences. There will be 4 scheduled visits (at Day -7, Day 0, Week 4 and Week 12). After screening period in which eligibility criteria were confirmed, subjects with hypertension will be randomized in a 1:1 ratio to receive treatment with either bisoprolol or atenolol. Hemodynamic measurements will be made at baseline, Week 4, Week 12 and biochemical measurements will be made at baseline (Day 0) and at Week 12.
Interventions
DRUGBisoprolol
Bisoprolol tablet will be administered orally at a dose of 5 milligram (mg) once daily in the morning for 12 weeks.
DRUGAtenolol
Atenolol tablet will be administered orally at a dose of 50 mg once daily in the morning for 12 weeks.
Sponsors
Merck Ltd.
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* An antihypertensive-naive subject or a subject who has not been taking the previously administered antihypertensive agent for at least 4 weeks prior to screening * Subjects aged between 20 and 75 years, inclusive * Subjects with systolic blood pressure (SBP) greater than or equal to 140 millimeter of mercury (mmHg) and less than 180 mmHg or diastolic blood pressure (DBP) greater than or equal to 90 mmHg and less than 110 mmHg
Exclusion criteria
* Subjects with secondary hypertension * Subjects with renal impairment (Creatinine greater than 150 micromoles/liter \[mcmol/L\] or Creatinine greater than 1.7 mg/deciliter \[dL\]) * Subjects with severe hypertension (Stage III) SBP greater than or equal to 180 mmHg or DBP greater than or equal to 110 mmHg * Subjects with congestive heart failure, acute myocardial infarction, unstable angina * Subjects with moderate bronchial asthma, chronic obstructive pulmonary disease * Subjects with symptomatic bradycardia, radial artery injury, second degree or third degree atrioventricular (AV) block, atrial fibrillation, atrial flutter, left bundle branch block (LBBB) * Subjects with a history of hypersensitivity to bisoprolol and atenolol products * Pregnancy or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12 | Baseline and Week 12 | The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 12 was calculated as APP at Week 12 minus APP at baseline. |
| Change From Baseline in Aortic Pulse Pressure (APP) in Per Protocol (PP) Population at Week 12 | Baseline and Week 12 | The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 12 was calculated as APP at Week 12 minus APP at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 4 and Week 12 | Baseline, Week 4 and Week 12 | Pulse wave velocity (PWV) is used as a measure of arterial stiffness, which is a measure of the cushioning functioning of major vessels like the aorta. The velocity of the Pulse wave (PW) along an artery is dependent on the stiffness of that artery. The change in cfPWV at Week 4 and Week 12 was calculated as cfPWV at Week 4 and Week 12 minus cfPWV at baseline. |
| Change From Baseline in Heart Rate at Week 4 and Week 12 | Baseline, Week 4 and Week 12 | The change in heart rate at Week 4 and Week 12 was calculated as heart rate at Week 4 and Week 12 minus heart rate at baseline. |
| Change From Baseline in Aortic Pulse Pressure (APP) at Week 4 | Baseline and Week 4 | The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 4 was calculated as APP at Week 4 minus APP at baseline. |
| Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Baseline, Week 4 and Week 12 | The change in aortic BP (aortic systolic blood pressure \[SBP\], aortic diastolic blood pressure \[DBP\] and aortic mean blood pressure \[BP\]) at Week 4 and Week 12 was calculated as aortic BP (aortic SBP, aortic DBP and aortic mean BP) at Week 4 and Week 12 minus aortic BP (aortic SBP, aortic DBP and aortic mean BP) at baseline. |
| Change From Baseline in Blood Glucose Levels at Week 12 | Baseline and Week 12 | The change in blood glucose level at Week 12 was calculated as blood glucose level at Week 12 minus blood glucose level at baseline. |
| Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Baseline, Week 4 and Week 12 | The change in brachial BP (brachial SBP, brachial DBP and brachial mean BP) at Week 4 and Week 12 was calculated as brachial BP (brachial SBP, brachial DBP and brachial mean BP) at Week 4 and Week 12 minus brachial BP (brachial SBP, brachial DBP and brachial mean BP) at baseline. |
| Number of Participants With Adverse Events (AEs) | Baseline up to Week 14 (follow-up visit) | An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. |
| Change From Baseline in Lipid Levels at Week 12 | Baseline and Week 12 | The lipid levels evaluated were total cholesterol, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol blood concentrations. The change in lipid levels at Week 12 was calculated as lipid levels at Week 12 minus lipid levels at baseline. |
| Change From Baseline in Aortic Augmentation Index (AIx) at Week 4 and Week 12 | Baseline, Week 4 and Week 12 | Augmentation index is a composite measure of wave reflection and systemic arterial stiffness which was calculated as the difference between the second and first systolic peaks. The change in AIx at Week 4 and Week 12 was calculated as AIx at Week 4 and Week 12 minus AIx at baseline. |
Countries
South Korea
Participant flow
Pre-assignment details
A total of 228 participants were screened for the study, out of which 19 were screen failures and 209 participants received the study medication.
Participants by arm
| Arm | Count |
|---|---|
| Bisoprolol Single dose of bisoprolol tablet (CONCOR®) administered orally at a dose of 5 milligram (mg) daily every morning for 12 weeks. | 105 |
| Atenolol Single dose of atenolol tablet (TENORMIN®) administered orally at a dose of 50 mg daily every morning for 12 weeks. | 104 |
| Total | 209 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Due to arrhythmia/bradycardia | 1 | 1 |
| Overall Study | Inclusion/exclusion criteria | 1 | 3 |
| Overall Study | No blood pressure (BP) control | 3 | 0 |
| Overall Study | Participant not returning for next visit | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 7 |
Baseline characteristics
| Characteristic | Bisoprolol | Atenolol | Total |
|---|---|---|---|
| Age, Continuous | 52.0 Years STANDARD_DEVIATION 11.2 | 52.2 Years STANDARD_DEVIATION 9.3 | 52.2 Years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 39 Participants | 46 Participants | 85 Participants |
| Sex: Female, Male Male | 66 Participants | 58 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 105 | 29 / 104 |
| serious Total, serious adverse events | 7 / 105 | 3 / 104 |
Outcome results
Primary
Change From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12
The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 12 was calculated as APP at Week 12 minus APP at baseline.
Time frame: Baseline and Week 12
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure. n signifies those participants who were evaluated for this measure at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Change From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12 | Baseline (n=96, 95) | 47.49 Millimeter of mercury (mmHg) | Standard Deviation 11.33 |
| Bisoprolol | Change From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12 | Change in APP at Week 12 (n=90, 89) | -4.40 Millimeter of mercury (mmHg) | Standard Deviation 9.29 |
| Atenolol | Change From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12 | Baseline (n=96, 95) | 45.93 Millimeter of mercury (mmHg) | Standard Deviation 11.62 |
| Atenolol | Change From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12 | Change in APP at Week 12 (n=90, 89) | -3.69 Millimeter of mercury (mmHg) | Standard Deviation 8.86 |
Comparison: Change in APP at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.594395% CI: [-1.89, 3.29]t-test, 2 sided
Primary
Change From Baseline in Aortic Pulse Pressure (APP) in Per Protocol (PP) Population at Week 12
The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 12 was calculated as APP at Week 12 minus APP at baseline.
Time frame: Baseline and Week 12
Population: Per protocol (PP) population included those participants for whom primary and secondary efficacy endpoints were all measured, and who did not meet the withdrawal criteria and showed 75 percent of medication compliance.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Change From Baseline in Aortic Pulse Pressure (APP) in Per Protocol (PP) Population at Week 12 | Baseline | 46.87 mmHg | Standard Deviation 11.34 |
| Bisoprolol | Change From Baseline in Aortic Pulse Pressure (APP) in Per Protocol (PP) Population at Week 12 | Change in APP at Week 12 | -4.33 mmHg | Standard Deviation 9.66 |
| Atenolol | Change From Baseline in Aortic Pulse Pressure (APP) in Per Protocol (PP) Population at Week 12 | Baseline | 46.53 mmHg | Standard Deviation 11.66 |
| Atenolol | Change From Baseline in Aortic Pulse Pressure (APP) in Per Protocol (PP) Population at Week 12 | Change in APP at Week 12 | -3.89 mmHg | Standard Deviation 9.07 |
p-value: 0.756195% CI: [-2.36, 3.24]t-test, 2 sided
Secondary
Change From Baseline in Aortic Augmentation Index (AIx) at Week 4 and Week 12
Augmentation index is a composite measure of wave reflection and systemic arterial stiffness which was calculated as the difference between the second and first systolic peaks. The change in AIx at Week 4 and Week 12 was calculated as AIx at Week 4 and Week 12 minus AIx at baseline.
Time frame: Baseline, Week 4 and Week 12
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure. n signifies those participants who were evaluated for this measure at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Change From Baseline in Aortic Augmentation Index (AIx) at Week 4 and Week 12 | Change in AIx at Week 4 (n=96, 95) | -1.56 Ratio | Standard Deviation 10.43 |
| Bisoprolol | Change From Baseline in Aortic Augmentation Index (AIx) at Week 4 and Week 12 | Change in AIx at Week 12 (n=90, 89) | 0.61 Ratio | Standard Deviation 9.18 |
| Atenolol | Change From Baseline in Aortic Augmentation Index (AIx) at Week 4 and Week 12 | Change in AIx at Week 12 (n=90, 89) | 1.21 Ratio | Standard Deviation 9.41 |
| Atenolol | Change From Baseline in Aortic Augmentation Index (AIx) at Week 4 and Week 12 | Change in AIx at Week 4 (n=96, 95) | -0.01 Ratio | Standard Deviation 10.14 |
Comparison: Change in AIx at Week 4: p-value was calculated by 2 sided t-test.p-value: 0.2987t-test, 2 sided
Comparison: Change in AIx at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.6584t-test, 2 sided
Secondary
Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12
The change in aortic BP (aortic systolic blood pressure \[SBP\], aortic diastolic blood pressure \[DBP\] and aortic mean blood pressure \[BP\]) at Week 4 and Week 12 was calculated as aortic BP (aortic SBP, aortic DBP and aortic mean BP) at Week 4 and Week 12 minus aortic BP (aortic SBP, aortic DBP and aortic mean BP) at baseline.
Time frame: Baseline, Week 4 and Week 12
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure. n signifies those participants who were evaluated for this measure at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic DBP at Week 12 (n=90, 89) | -10.94 mmHg | Standard Deviation 9.53 |
| Bisoprolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic SBP at Week 4 (n=96, 95) | -13.90 mmHg | Standard Deviation 12.68 |
| Bisoprolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic mean BP at Week 4 (n=96, 95) | -11.88 mmHg | Standard Deviation 8.6 |
| Bisoprolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic DBP at Week 4 (n=96, 95) | -10.86 mmHg | Standard Deviation 8.23 |
| Bisoprolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic mean BP at Week 12 (n=90, 89) | -12.41 mmHg | Standard Deviation 10.84 |
| Bisoprolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic SBP at Week 12 (n=90, 89) | -15.34 mmHg | Standard Deviation 15.11 |
| Atenolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic mean BP at Week 12 (n=90, 89) | -10.24 mmHg | Standard Deviation 10.28 |
| Atenolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic SBP at Week 12 (n=90, 89) | -12.71 mmHg | Standard Deviation 14.67 |
| Atenolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic DBP at Week 4 (n=96, 95) | -9.47 mmHg | Standard Deviation 8.23 |
| Atenolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic DBP at Week 12 (n=90, 89) | -9.01 mmHg | Standard Deviation 8.79 |
| Atenolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic mean BP at Week 4 (n=96, 95) | -10.84 mmHg | Standard Deviation 9.07 |
| Atenolol | Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12 | Change in aortic SBP at Week 4 (n=96, 95) | -13.57 mmHg | Standard Deviation 12.73 |
Comparison: Change in SBP at Week 4: p-value was calculated by 2 sided t-test.p-value: 0.8589t-test, 2 sided
Comparison: Change in SBP at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.2223t-test, 2 sided
Comparison: Change in DBP at Week 4: p-value was calculated by 2 sided t-test.p-value: 0.2443t-test, 2 sided
Comparison: Change in DBP at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.1481t-test, 2 sided
Comparison: Change in mean BP at Week 4: p-value was calculated by 2 sided t-test.p-value: 0.4188t-test, 2 sided
Comparison: Change in mean BP at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.1586t-test, 2 sided
Secondary
Change From Baseline in Aortic Pulse Pressure (APP) at Week 4
The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 4 was calculated as APP at Week 4 minus APP at baseline.
Time frame: Baseline and Week 4
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bisoprolol | Change From Baseline in Aortic Pulse Pressure (APP) at Week 4 | -3.02 mmHg | Standard Deviation 10.56 |
| Atenolol | Change From Baseline in Aortic Pulse Pressure (APP) at Week 4 | -4.09 mmHg | Standard Deviation 8.72 |
p-value: 0.4447t-test, 2 sided
Secondary
Change From Baseline in Blood Glucose Levels at Week 12
The change in blood glucose level at Week 12 was calculated as blood glucose level at Week 12 minus blood glucose level at baseline.
Time frame: Baseline and Week 12
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bisoprolol | Change From Baseline in Blood Glucose Levels at Week 12 | -0.23 Millimoles per liter (mmol/L) | Standard Deviation 17.85 |
| Atenolol | Change From Baseline in Blood Glucose Levels at Week 12 | -0.45 Millimoles per liter (mmol/L) | Standard Deviation 12.03 |
p-value: 0.9244t-test, 2 sided
Secondary
Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12
The change in brachial BP (brachial SBP, brachial DBP and brachial mean BP) at Week 4 and Week 12 was calculated as brachial BP (brachial SBP, brachial DBP and brachial mean BP) at Week 4 and Week 12 minus brachial BP (brachial SBP, brachial DBP and brachial mean BP) at baseline.
Time frame: Baseline, Week 4 and Week 12
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure. n signifies those participants who were evaluated for this measure at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial SBP at Week 4 (n=96, 95) | -17.45 mmHg | Standard Deviation 11.74 |
| Bisoprolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial SBP at Week 12 (n=90, 89) | -19.10 mmHg | Standard Deviation 14.55 |
| Bisoprolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial DBP at Week 4 (n=96, 95) | -12.70 mmHg | Standard Deviation 9.01 |
| Bisoprolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial DBP at Week 12 (n=90, 89) | -13.39 mmHg | Standard Deviation 9.9 |
| Bisoprolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial mean BP at Week 4 (n=96, 95) | -14.28 mmHg | Standard Deviation 9.28 |
| Bisoprolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial mean BP at Week 12 (n=90, 89) | -15.29 mmHg | Standard Deviation 10.78 |
| Atenolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial mean BP at Week 4 (n=96, 95) | -13.41 mmHg | Standard Deviation 8.94 |
| Atenolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial SBP at Week 4 (n=96, 95) | -17.52 mmHg | Standard Deviation 12.53 |
| Atenolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial DBP at Week 12 (n=90, 89) | -10.61 mmHg | Standard Deviation 8.79 |
| Atenolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial SBP at Week 12 (n=90, 89) | -17.63 mmHg | Standard Deviation 13.74 |
| Atenolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial mean BP at Week 12 (n=90, 89) | -12.95 mmHg | Standard Deviation 9.96 |
| Atenolol | Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12 | Change in brachial DBP at Week 4 (n=96, 95) | -11.36 mmHg | Standard Deviation 8.34 |
Comparison: Change in SBP at Week 4: p-value was calculated by 2 sided t-test.p-value: 0.9692t-test, 2 sided
Comparison: Change in SBP at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.4731t-test, 2 sided
Comparison: Change in DBP at Week 4: p-value was calculated by 2 sided t-test.p-value: 0.2876t-test, 2 sided
Comparison: Change in DBP at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.042t-test, 2 sided
Comparison: Change in mean BP at Week 4: p-value was calculated by 2 sided t-test.p-value: 0.51t-test, 2 sided
Comparison: Change in mean BP at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.1207t-test, 2 sided
Secondary
Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 4 and Week 12
Pulse wave velocity (PWV) is used as a measure of arterial stiffness, which is a measure of the cushioning functioning of major vessels like the aorta. The velocity of the Pulse wave (PW) along an artery is dependent on the stiffness of that artery. The change in cfPWV at Week 4 and Week 12 was calculated as cfPWV at Week 4 and Week 12 minus cfPWV at baseline.
Time frame: Baseline, Week 4 and Week 12
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure. n signifies those participants who were evaluated for this measure at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 4 and Week 12 | Change in cfPWV at Week 4 (n=96, 95) | -0.60 Meters per second (m/s) | Standard Deviation 1.33 |
| Bisoprolol | Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 4 and Week 12 | Change cfPWV at Week 12 (n=90, 89) | -0.72 Meters per second (m/s) | Standard Deviation 1.4 |
| Atenolol | Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 4 and Week 12 | Change in cfPWV at Week 4 (n=96, 95) | -0.81 Meters per second (m/s) | Standard Deviation 1.15 |
| Atenolol | Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 4 and Week 12 | Change cfPWV at Week 12 (n=90, 89) | -0.87 Meters per second (m/s) | Standard Deviation 1.56 |
Comparison: Change in cfPWV at Week 4: p-value was calculated by 2 sided t-test.p-value: 0.2511t-test, 2 sided
Comparison: Change in cfPWV at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.5007t-test, 2 sided
Secondary
Change From Baseline in Heart Rate at Week 4 and Week 12
The change in heart rate at Week 4 and Week 12 was calculated as heart rate at Week 4 and Week 12 minus heart rate at baseline.
Time frame: Baseline, Week 4 and Week 12
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure. n signifies those participants who were evaluated for this measure at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Change From Baseline in Heart Rate at Week 4 and Week 12 | Change in heart rate at Week 4 (n= 96, 95) | -6.21 Beats per minute (bpm) | Standard Deviation 7.72 |
| Bisoprolol | Change From Baseline in Heart Rate at Week 4 and Week 12 | Change heart rate at Week 12 (n= 90, 89) | -8.64 Beats per minute (bpm) | Standard Deviation 7.95 |
| Atenolol | Change From Baseline in Heart Rate at Week 4 and Week 12 | Change in heart rate at Week 4 (n= 96, 95) | -6.20 Beats per minute (bpm) | Standard Deviation 8.25 |
| Atenolol | Change From Baseline in Heart Rate at Week 4 and Week 12 | Change heart rate at Week 12 (n= 90, 89) | -7.84 Beats per minute (bpm) | Standard Deviation 9.15 |
Comparison: Change in heart rate at Week 4: p-value was calculated by 2 sided t-test.p-value: 0.9943t-test, 2 sided
Comparison: Change in heart rate at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.523t-test, 2 sided
Secondary
Change From Baseline in Lipid Levels at Week 12
The lipid levels evaluated were total cholesterol, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol blood concentrations. The change in lipid levels at Week 12 was calculated as lipid levels at Week 12 minus lipid levels at baseline.
Time frame: Baseline and Week 12
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Change From Baseline in Lipid Levels at Week 12 | Change in Total cholesterol at Week 12 | -3.43 Milligram/decilitre (mg/dL) | Standard Deviation 23.35 |
| Bisoprolol | Change From Baseline in Lipid Levels at Week 12 | Change in LDL-cholesterol at Week 12 | -2.29 Milligram/decilitre (mg/dL) | Standard Deviation 19.01 |
| Bisoprolol | Change From Baseline in Lipid Levels at Week 12 | Change in HDL-cholesterol at Week 12 | -1.58 Milligram/decilitre (mg/dL) | Standard Deviation 7.13 |
| Atenolol | Change From Baseline in Lipid Levels at Week 12 | Change in Total cholesterol at Week 12 | -0.37 Milligram/decilitre (mg/dL) | Standard Deviation 24.79 |
| Atenolol | Change From Baseline in Lipid Levels at Week 12 | Change in LDL-cholesterol at Week 12 | 1.31 Milligram/decilitre (mg/dL) | Standard Deviation 17.77 |
| Atenolol | Change From Baseline in Lipid Levels at Week 12 | Change in HDL-cholesterol at Week 12 | -3.02 Milligram/decilitre (mg/dL) | Standard Deviation 7.54 |
Comparison: Change in Total cholesterol at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.396t-test, 2 sided
Comparison: Change in LDL-cholesterol at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.1919t-test, 2 sided
Comparison: Change in HDL-cholesterol at Week 12: p-value was calculated by 2 sided t-test.p-value: 0.1896t-test, 2 sided
Secondary
Number of Participants With Adverse Events (AEs)
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Time frame: Baseline up to Week 14 (follow-up visit)
Population: ITT population included all participants who had received at least 1 dose of the study medication or comparator and at least 1 post-dose measurement of aortic pulse pressure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bisoprolol | Number of Participants With Adverse Events (AEs) | 36 Participants |
| Atenolol | Number of Participants With Adverse Events (AEs) | 32 Participants |