Hypertrophy, Left Ventricular
Conditions
Keywords
left ventricular hypertrophy (LVH), echocardiogram, left ventricular mass regression, cardiac MRI, left ventricular mass index (LVMI)hypertension
Brief summary
This study is designed to compare the effects of COREG MR (carvedilol modified release formulation) to atenolol on indices of left ventricular dimensions when added to standardized angiotensin converting enzyme (ACE) inhibition, and to the effect of ACE inhibition alone. Subjects with LVH (left ventricular hypertrophy) and hypertension will be studied. The primary endpoint will be the change in left ventricular mass index (LVMI) characterized by magnetic resonance imaging (MRI) following 12 months of treatment. Secondary endpoints include the change in LV (left ventricular) mass, LV wall thickness, diastolic left ventricular filling parameters, and left ventricular ejection fraction by echocardiographic methods at Treatment Month 12. Composite outcomes and individual event data will also be evaluated by treatment group.
Detailed description
A Randomized, Double-Blind, Multi-Center Study Comparing the Effects of Carvedilol Modified Release Formulation (COREG MR) and Atenolol in Combination with and Compared to an Angiotensin Converting Enzyme Inhibitor (Lisinopril) on Left Ventricular Mass Regression in Hypertensive Patients with Left Ventricular Hypertrophy (LVH).
Interventions
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Stage 1 or Stage 2 hypertension. * Left ventricular hypertrophy.
Exclusion criteria
* In atrial fibrillation. * Takes beta-blocker for MI (myocardial infarction) or arrhythmia. * Has uncontrolled diabetes, uncontrollable or symptomatic arrhythmias, unstable angina, second or third degree heart block, history of MI, COPD (chronic obstructive pulmonary disease), liver or kidney disease. * Uses beta-2-agonists. * Unable to undergo MRI (magnetic resonance imaging). * Females of childbearing potential.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Magnetic Resonance Imaging (MRI) at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the Last Observation Carried Forward [LOCF] analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | LVMI was measured by MRI at Baseline and after 12 months of treatment/Month 12. A reduction in left ventricular mass, calculated as LVMI, of 5 g/m\^2 was assumed to be clinically meaningful. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | LV Mass was measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. |
| Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | LVMI was measured by echogradiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. |
| Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was available) | LVMIH was measured by echogradiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. |
| Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | LV Mass was measured by echocardiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. |
| Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | LV filling parameters, LV E-Volume and LV A-Volume, were measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. These filling parameters represent the volumes of blood filling the ventricle during the passive filling phase (E-volume) and the active filling phase caused by atrial contraction (A-volume). |
| Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | LV End Systolic and Diastolic Volumes and Ejection Fraction were measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. The ejection fraction is the fraction of the blood volume available at the end of diastole that is pumped out of the ventricules during systole. |
| Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | LVMIH was measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. LV mass depends on body size. One method of determining whether an individual has LV hypertrophy relates LV mass to height raised to a power of 2.7. |
| Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | Systolic and Diastolic BP were measured at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. |
| Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF was used | BNP concentration (picagram per milliter) was measured at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and was calculated as 100 x (exponent (mean change on log scale) -1) \[Change is the Month 12 value (or value after 12 months of treatment) minus the Baseline value\]. |
| Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF was used) | CRP concentration (milligrams per deciliter) was measured at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and calculated as 100 x (exponent (mean change on log scale) - 1). \[Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.\] |
| Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF was used) | Plasma lipid concentrations (milligrams per deciliter) were measured at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and calculated as 100 x (exponent(mean change on log scale) - 1). \[Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.\] |
| Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF was used) | Urinary ACR (micrograms per milligram) was determined at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and was calculated as 100 x (exponent (exponent (mean change on log scale) - 1. \[Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.\] |
| Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | LV End Systolic and Diastolic Volumes and Ejection Fraction were measured by echocardiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. |
Countries
United States
Participant flow
Pre-assignment details
Following screening, 413 participants were enrolled into the study to begin an open-label run-in phase with lisinopril 10 mg once daily (OD) for 1 week and then lisinopril 20 mg OD for 1 week. Of these participants, 287 were randomized to 1 of the 3 treatment regimens.
Participants by arm
| Arm | Count |
|---|---|
| Carvedilol CR Carvedilol controlled release (CR) 20 to 80 mg once daily (OD) plus lisinopril 20 mg OD. Participants were titrated from the starting dosage to higher dosages until their blood pressure was controlled. Participants continued to receive lisinopril 20 mg OD throughout the study. (In the protocol, carvedilol CR was referred to as carvedilol modified-release \[MR\].) | 91 |
| Atenolol Atenolol 50 to 100 mg OD plus lisinopril 20 mg OD. Participants were titrated from the starting dosage to higher dosages until their blood pressure was controlled. Participants continued to receive lisinopril 20 mg OD throughout the study. | 100 |
| Lisinopril Lisinopril 10 to 40 mg OD plus lisinopril 20 mg OD. Participants were titrated from the starting dosage to higher dosages until their blood pressure was controlled. Participants continued to receive lisinopril 20 mg OD throughout the study. | 96 |
| Total | 287 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 14 | 12 | 17 |
| Overall Study | Amendment 4: > Month 12 | 5 | 7 | 5 |
| Overall Study | Blood Pressure Not Controlled | 1 | 0 | 0 |
| Overall Study | Consent Withdrawn | 3 | 3 | 5 |
| Overall Study | Incorrectly Randomized | 0 | 0 | 2 |
| Overall Study | Investigator Not at Site | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 3 | 1 | 2 |
| Overall Study | Lost to Follow-up | 6 | 3 | 7 |
| Overall Study | Non-compliance | 1 | 0 | 2 |
| Overall Study | Protocol Amendment | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 2 | 0 |
| Overall Study | Site Closed Study | 0 | 2 | 0 |
| Overall Study | Stopped Study Medication | 0 | 0 | 1 |
| Overall Study | Study Medication Not Tapered | 0 | 1 | 0 |
| Overall Study | Subject Left Site Location | 1 | 0 | 0 |
| Overall Study | Woman of Child-bearing Potential | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Carvedilol CR | Total | Lisinopril | Atenolol |
|---|---|---|---|---|
| Age, Continuous | 56.6 years STANDARD_DEVIATION 10.53 | 56.7 years STANDARD_DEVIATION 10.52 | 55.9 years STANDARD_DEVIATION 10.09 | 57.4 years STANDARD_DEVIATION 10.95 |
| Gender Female | 40 Participants | 128 Participants | 47 Participants | 41 Participants |
| Gender Male | 51 Participants | 159 Participants | 49 Participants | 59 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 17 participants | 60 participants | 17 participants | 26 participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 0 participants | 2 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Arabic/North African Heritage | 1 participants | 2 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 3 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Mixed Race | 1 participants | 2 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Not Reported | 3 participants | 12 participants | 4 participants | 5 participants |
| Race/Ethnicity, Customized White/Caucasian | 67 participants | 206 participants | 72 participants | 67 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 54 / — | 61 / — | 52 / — |
| serious Total, serious adverse events | 4 / — | 6 / — | 12 / — |
Outcome results
Primary
Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Magnetic Resonance Imaging (MRI) at Month 12
LVMI was measured by MRI at Baseline and after 12 months of treatment/Month 12. A reduction in left ventricular mass, calculated as LVMI, of 5 g/m\^2 was assumed to be clinically meaningful. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.
Time frame: Baseline and Month 12 (If Month 12 data were not available, the Last Observation Carried Forward [LOCF] analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Population: All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol CR | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Magnetic Resonance Imaging (MRI) at Month 12 | -6.34 grams per meters squared (g/m^2) | Standard Error 0.85 |
| Atenolol | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Magnetic Resonance Imaging (MRI) at Month 12 | -6.67 grams per meters squared (g/m^2) | Standard Error 0.756 |
| Lisinopril | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Magnetic Resonance Imaging (MRI) at Month 12 | -7.94 grams per meters squared (g/m^2) | Standard Error 0.85 |
Comparison: The null hypotheses (tested hierarchically) were that the effect of carvedilol CR + lisinopril on LV mass regression was no different than the effect of atenolol + lisinopril, and that the effect of carvedilol CR + lisinopril was no different than the effect of lisinopril + lisinopril. The primary analysis was based on an analysis of covariance (ANCOVA) with a model adjusting for treatment, stratification by hypertension class, region, and baseline value, at a 0.05 level of significance.p-value: 0.765195% CI: [-1.83, 2.49]ANCOVA
p-value: 0.171195% CI: [-0.7, 3.9]ANCOVA
Secondary
Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12
LV filling parameters, LV E-Volume and LV A-Volume, were measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. These filling parameters represent the volumes of blood filling the ventricle during the passive filling phase (E-volume) and the active filling phase caused by atrial contraction (A-volume).
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Population: All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Carvedilol CR | Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 | LV E-volume | 0.364 milliliters (mL) | Standard Error 2.2853 |
| Carvedilol CR | Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 | LV A-volume | -0.513 milliliters (mL) | Standard Error 1.3624 |
| Atenolol | Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 | LV E-volume | 6.763 milliliters (mL) | Standard Error 2.387 |
| Atenolol | Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 | LV A-volume | -0.565 milliliters (mL) | Standard Error 1.5154 |
| Lisinopril | Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 | LV E-volume | -3.406 milliliters (mL) | Standard Error 2.8779 |
| Lisinopril | Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 | LV A-volume | 1.088 milliliters (mL) | Standard Error 1.563 |
Secondary
Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12
LV Mass was measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Population: All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol CR | Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12 | -13.74 grams (g) | Standard Error 1.732 |
| Atenolol | Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12 | -14.17 grams (g) | Standard Error 1.54 |
| Lisinopril | Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12 | -17.17 grams (g) | Standard Error 1.734 |
Secondary
Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12
LVMIH was measured by echogradiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was available)
Population: All randomized participants who had a valid echocardiogram at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol CR | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12 | -11.78 g/m raised to 2.7 (g/(m^2.7)) | Standard Error 2.292 |
| Atenolol | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12 | -12.51 g/m raised to 2.7 (g/(m^2.7)) | Standard Error 2.1 |
| Lisinopril | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12 | -11.61 g/m raised to 2.7 (g/(m^2.7)) | Standard Error 2.28 |
Secondary
Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12
LVMIH was measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. LV mass depends on body size. One method of determining whether an individual has LV hypertrophy relates LV mass to height raised to a power of 2.7.
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Population: All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol CR | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12 | -3.19 g/m raised to 2.7 (g/(m^2.7)) | Standard Error 0.407 |
| Atenolol | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12 | -3.37 g/m raised to 2.7 (g/(m^2.7)) | Standard Error 0.361 |
| Lisinopril | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12 | -3.98 g/m raised to 2.7 (g/(m^2.7)) | Standard Error 0.407 |
Secondary
Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12
LVMI was measured by echogradiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Population: All randomized participants who had a valid echocardiogram at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol CR | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12 | -20.35 grams per meters squared (g/m^2) | Standard Error 4.027 |
| Atenolol | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12 | -20.06 grams per meters squared (g/m^2) | Standard Error 3.672 |
| Lisinopril | Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12 | -18.48 grams per meters squared (g/m^2) | Standard Error 3.998 |
Secondary
Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12
LV End Systolic and Diastolic Volumes and Ejection Fraction were measured by echocardiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Population: All randomized participants who had a valid echocardiogram at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Carvedilol CR | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV End Diastolic Volume | -3.07 milliliters (mL) | Standard Error 3.389 |
| Carvedilol CR | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV End Systolic Volume | -3.38 milliliters (mL) | Standard Error 2.067 |
| Carvedilol CR | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV Ejection Fraction | 1.03 milliliters (mL) | Standard Error 0.751 |
| Atenolol | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV End Diastolic Volume | -3.64 milliliters (mL) | Standard Error 3.108 |
| Atenolol | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV End Systolic Volume | -4.74 milliliters (mL) | Standard Error 1.892 |
| Atenolol | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV Ejection Fraction | 2.33 milliliters (mL) | Standard Error 0.687 |
| Lisinopril | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV End Systolic Volume | -5.34 milliliters (mL) | Standard Error 2.086 |
| Lisinopril | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV Ejection Fraction | 0.63 milliliters (mL) | Standard Error 0.756 |
| Lisinopril | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV End Diastolic Volume | -9.37 milliliters (mL) | Standard Error 3.42 |
Secondary
Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12
LV End Systolic and Diastolic Volumes and Ejection Fraction were measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. The ejection fraction is the fraction of the blood volume available at the end of diastole that is pumped out of the ventricules during systole.
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Population: All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Carvedilol CR | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV End Diastolic Volume | -2.86 milliliters (mL) | Standard Error 2.848 |
| Carvedilol CR | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV End Systolic Volume | -1.44 milliliters (mL) | Standard Error 1.578 |
| Carvedilol CR | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV Ejection Fraction | 0.08 milliliters (mL) | Standard Error 0.685 |
| Atenolol | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV End Diastolic Volume | -2.45 milliliters (mL) | Standard Error 2.522 |
| Atenolol | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV End Systolic Volume | -4.29 milliliters (mL) | Standard Error 1.397 |
| Atenolol | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV Ejection Fraction | 2.16 milliliters (mL) | Standard Error 0.607 |
| Lisinopril | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV End Systolic Volume | -3.04 milliliters (mL) | Standard Error 1.581 |
| Lisinopril | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV Ejection Fraction | -0.01 milliliters (mL) | Standard Error 0.685 |
| Lisinopril | Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV End Diastolic Volume | -7.45 milliliters (mL) | Standard Error 2.858 |
Secondary
Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12
LV Mass was measured by echocardiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Population: All randomized participants who had a valid echocardiogram at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol CR | Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12 | -45.76 grams | Standard Error 8.338 |
| Atenolol | Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12 | -40.56 grams | Standard Error 7.645 |
| Lisinopril | Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12 | -38.58 grams | Standard Error 8.296 |
Secondary
Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12
Systolic and Diastolic BP were measured at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Population: All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Carvedilol CR | Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 | Systolic blood pressure | -21.32 mmHg (millimeters of mercury) | Standard Error 1.755 |
| Carvedilol CR | Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 | Diastolic blood pressure | -12.77 mmHg (millimeters of mercury) | Standard Error 1.103 |
| Atenolol | Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 | Systolic blood pressure | -21.12 mmHg (millimeters of mercury) | Standard Error 1.535 |
| Atenolol | Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 | Diastolic blood pressure | -14.05 mmHg (millimeters of mercury) | Standard Error 0.976 |
| Lisinopril | Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 | Systolic blood pressure | -22.53 mmHg (millimeters of mercury) | Standard Error 1.708 |
| Lisinopril | Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 | Diastolic blood pressure | -11.13 mmHg (millimeters of mercury) | Standard Error 1.117 |
Secondary
Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12
Urinary ACR (micrograms per milligram) was determined at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and was calculated as 100 x (exponent (exponent (mean change on log scale) - 1. \[Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.\]
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF was used)
Population: All randomized participants who had a valid measurements at Baseline and Month 12 (LOCF)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Carvedilol CR | Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12 | -27.1 percentage of change |
| Atenolol | Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12 | -20.1 percentage of change |
| Lisinopril | Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12 | -21.5 percentage of change |
Secondary
Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12
BNP concentration (picagram per milliter) was measured at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and was calculated as 100 x (exponent (mean change on log scale) -1) \[Change is the Month 12 value (or value after 12 months of treatment) minus the Baseline value\].
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF was used
Population: All randomized participants who had a valid measurements at Baseline and Month 12 (LOCF)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Carvedilol CR | Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12 | 51.7 percentage of change |
| Atenolol | Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12 | 48.3 percentage of change |
| Lisinopril | Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12 | -39.1 percentage of change |
Secondary
Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12
CRP concentration (milligrams per deciliter) was measured at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and calculated as 100 x (exponent (mean change on log scale) - 1). \[Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.\]
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF was used)
Population: All randomized participants who had a valid measurements at Baseline and Month 12 (LOCF)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Carvedilol CR | Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12 | -10.63 percentage of change |
| Atenolol | Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12 | -3.22 percentage of change |
| Lisinopril | Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12 | 2.70 percentage of change |
Secondary
Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12
Plasma lipid concentrations (milligrams per deciliter) were measured at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and calculated as 100 x (exponent(mean change on log scale) - 1). \[Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.\]
Time frame: Baseline and Month 12 (If Month 12 data were not available, the LOCF was used)
Population: All randomized participants who had a valid measurements at Baseline and Month 12 (LOCF)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Carvedilol CR | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Total cholesterol | 0.7 percentage of change |
| Carvedilol CR | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Low-density lipid cholesterol | 0.0 percentage of change |
| Carvedilol CR | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | High-density lipid cholesterol | -4.3 percentage of change |
| Carvedilol CR | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Triglycerides | 11.0 percentage of change |
| Atenolol | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Triglycerides | 7.1 percentage of change |
| Atenolol | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Total cholesterol | -1.3 percentage of change |
| Atenolol | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | High-density lipid cholesterol | -4.7 percentage of change |
| Atenolol | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Low-density lipid cholesterol | -4.0 percentage of change |
| Lisinopril | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Triglycerides | 6.2 percentage of change |
| Lisinopril | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Low-density lipid cholesterol | -2.7 percentage of change |
| Lisinopril | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | High-density lipid cholesterol | -1.5 percentage of change |
| Lisinopril | Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Total cholesterol | -1.7 percentage of change |