Marfan Syndrome
Conditions
Keywords
Aortic Root Dissection, Aortic Root Dilation, Pediatric Heart Network
Brief summary
Marfan syndrome is a hereditary connective tissue disorder. Many individuals with this condition die because of the associated heart and blood vessel abnormalities. This study will compare the effectiveness of two medications, losartan and atenolol, at slowing aortic root enlargement in individuals with Marfan syndrome.
Detailed description
Marfan syndrome is an inheritable disorder that affects the body's connective tissue. An abnormal protein results in connective tissue that is weaker than normal. Because connective tissue is found throughout the body, Marfan syndrome can affect many body systems, including the skeleton, eyes, nervous system, skin, lungs, heart, and blood vessels. Overall, heart and blood vessel abnormalities are the leading cause of death in individuals with Marfan syndrome. A common blood vessel abnormality associated with this disease involves the aorta, which is the large artery that carries blood away from the heart to the rest of the body. The aortic root, the portion of the aorta that is attached to the heart, may enlarge and tear or even rupture. A tear or rupture is considered a life-threatening emergency. Recent studies have shown that the medication losartan may reduce aortic root growth and improve heart function. The purpose of this study is to compare the effectiveness of losartan versus atenolol at slowing aortic root growth in individuals with Marfan syndrome. This 3-year study will enroll individuals with Marfan syndrome. Participants will be randomly assigned to receive either losartan or atenolol on a daily basis. All participants will initially receive a low dose of their assigned medication. This dose will be gradually increased every 3 to 4 weeks until the maximum tolerated dose is reached. A continuous electrocardiogram (ECG) that monitors heart rate and activity in 24-hour intervals will be used to determine the proper dose increase for each participant. Participants will then receive the maximum tolerated dose for the remainder of the study. Study visits will occur at baseline and Months 6, 12, 24, and 36. Each study visit will include a physical examination, a medical history review, an ECG, an echocardiogram, and questionnaires. Additionally, at the baseline study visit blood will be collected for laboratory testing.
Interventions
DRUGLosartan Potassium
Losartan .3 - 1.4 mg/kg
DRUGAtenolol
Atenolol .5 - 4 mg/kg
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
FDA Office of Orphan Products Development
National Marfan Foundation
Carelon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 25 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Marfan syndrome, according to Ghent criteria (more information can be found in Appendix D of the protocol) * Aortic root Z-score greater than 3.0
Exclusion criteria
* Prior aortic surgery * Aortic root dimension at the sinuses of Valsalva greater than 5 cm * Planned aortic surgery within 6 months of study entry * Aortic dissection * Shprintzen-Goldberg syndrome * Loeys-Dietz syndrome * Therapeutic (i.e., for arrhythmia, ventricular dysfunction, or valve regurgitation) rather than prophylactic use of angiotensin-converting enzyme (ACE) inhibitor, beta-blocker, or calcium channel blocker * History of angioedema while taking an ACE inhibitor or beta-blocker * Intolerance to losartan or other angiotensin II receptor blocker (ARB) that resulted in termination of therapy * Intolerance to atenolol or other beta-blocker that resulted in termination of therapy * Kidney dysfunction (i.e., creatinine greater than the upper limit of age-related normal values) * Asthma of sufficient severity to prohibit the use of a beta-blocker * Chronic use of steroids and/or beta-adrenergic agents with exacerbations of asthma that are frequent (averaging three or more per year) or severe (requiring hospitalization) * Diabetes mellitus * Pregnant or planning to become pregnant within 36 months of study entry * Inability to complete study procedures, including history of poor acoustic windows (i.e., inability to obtain accurate measurement of aortic root)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score | Up to 3 years following randomization. | The rate of aortic root enlargement, expressed as the annual change in the maximum aortic-root-diameter z score indexed to body-surface area over a 3-year period following randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area. | Up to 3 years following randomization. | — |
| Annual Rate of Change in the Absolute Diameter of the Ascending Aorta | Up to 3 years following randomization. | — |
| Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area | Up to 3 years following randomization. | — |
| Annual Rate of Change in the Absolute Diameter of the Aortic Annulus | Up to 3 years following randomization. | — |
| Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area | Up to 3 years following randomization. | — |
| Annual Rate of Change in Weight | Up to 3 years following randomization. | — |
| Annual Rate of Change in Weight-for-age Z-score | Up to 3 years following randomization. | — |
| Annual Rate of Change in Weight-for-height Z-score | Up to 3 years following randomization. | — |
| Annual Rate of Change in Height | Up to 3 years following randomization. | — |
| Annual Rate of Change in Height-for-age Z-score | Up to 3 years following randomization. | — |
| Annual Rate of Change in Body Mass Index | Up to 3 years following randomization. | — |
| Annual Rate of Change in Body Mass Index for Age Z-score | Up to 3 years following randomization. | — |
| Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension | Up to 3 years following randomization. | The rate of change in the absolute dimension of the aortic root over a 3-year period following randomization |
| Annual Rate of Change in Upper to Lower Segment Ratio | Up to 3 years following randomization. | — |
| Number of Participants With Aortic Dissection. | Up to 3 years following randomization. | — |
| Event Rate of Aortic Dissection. | Up to 3 years following randomization. | Percentage of participants who had aortic dissection over a 3-year period following randomization. |
| Number of Participants With Aortic-root Surgery. | Up to 3 years following randomization. | — |
| Event Rate of Aortic-Root Surgery | Up to 3 years following randomization. | Percentage of participants who had aortic-root surgery over a 3-year period following randomization. |
| Number of Death. | Up to 3 years following randomization. | — |
| Event Rate of Death | Up to 3 years following randomization. | Percentage of participants who died over a 3-year period following randomization. |
| Number of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death. | Up to 3 years following randomization. | — |
| Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death. | Up to 3 years following randomization. | Percentage of participants who had aortic dissection, aortic-root surgery or death over a 3-year period following randomization |
| Adverse Drug Reactions Reported at the Baseline Visit | At baseline | — |
| Adverse Drug Reactions Reported During Routine Follow-up Surveillance | From 6 months to 3 years following randomization. | — |
| Annual Rate of Change in Arm Span to Height Ratio | Up to 3 years following randomization. | — |
Countries
Belgium, Canada, United States
Participant flow
Recruitment details
From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants into the study.
Pre-assignment details
For subjects on prophylactic therapy with atenolol or other BB, ARB, ACEi, or calcium-channel blocker, before the study, the drug will be weaned over a 14-day period. After that, a drug washout period of 14-21 days will take place before baseline assessment and randomization.
Participants by arm
| Arm | Count |
|---|---|
| Atenolol Participants with Marfan's syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate. | 303 |
| Losartan Participants with Marfan's syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg). | 305 |
| Total | 608 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 7 | 6 |
| Overall Study | Physician Decision | 4 | 2 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Underwent aortic root surgery | 10 | 18 |
| Overall Study | Withdrawal by Subject | 11 | 5 |
Baseline characteristics
| Characteristic | Atenolol | Losartan | Total |
|---|---|---|---|
| Age, Continuous | 11.5 years STANDARD_DEVIATION 6.5 | 11.0 years STANDARD_DEVIATION 6.2 | 11.2 years STANDARD_DEVIATION 6.3 |
| Age, Customized Child | 227 participants | 230 participants | 457 participants |
| Age, Customized Young adult | 76 participants | 75 participants | 151 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 46 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 266 Participants | 259 Participants | 525 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Family history of Marfan No | 115 participants | 109 participants | 224 participants |
| Family history of Marfan Unknown | 8 participants | 15 participants | 23 participants |
| Family history of Marfan Yes | 180 participants | 181 participants | 361 participants |
| Had medical history of cardiac surgery No | 297 participants | 299 participants | 596 participants |
| Had medical history of cardiac surgery Yes | 6 participants | 6 participants | 12 participants |
| Had medical history of cardiovascular disorder No | 264 participants | 269 participants | 533 participants |
| Had medical history of cardiovascular disorder Yes | 39 participants | 36 participants | 75 participants |
| Had medical history of endocrine disorder No | 296 participants | 305 participants | 601 participants |
| Had medical history of endocrine disorder Yes | 7 participants | 0 participants | 7 participants |
| Had medical history of neurodevelopmental disorder No | 247 participants | 244 participants | 491 participants |
| Had medical history of neurodevelopmental disorder Yes | 56 participants | 61 participants | 117 participants |
| Had medical history of psychiatric disorder No | 280 participants | 289 participants | 569 participants |
| Had medical history of psychiatric disorder Yes | 23 participants | 16 participants | 39 participants |
| Maximum aortic-root diameter, cm | 3.4 centimeter STANDARD_DEVIATION 0.7 | 3.4 centimeter STANDARD_DEVIATION 0.7 | 3.4 centimeter STANDARD_DEVIATION 0.7 |
| Maximum aortic-root diameter z-score <z-score of 4.5 | 197 participants | 191 participants | 388 participants |
| Maximum aortic-root diameter z-score ≥z-score of 4.5 | 106 participants | 114 participants | 220 participants |
| Maximum aortic-root diameter z-score | 4.0 z-score | 4.0 z-score | 4.0 z-score |
| Presence of causal FBN1 mutation No | 9 participants | 15 participants | 24 participants |
| Presence of causal FBN1 mutation Unknown | 201 participants | 202 participants | 403 participants |
| Presence of causal FBN1 mutation Yes | 93 participants | 88 participants | 181 participants |
| Prior use of beta-blocker No | 130 participants | 134 participants | 264 participants |
| Prior use of beta-blocker Yes | 173 participants | 171 participants | 344 participants |
| Race/Ethnicity, Customized Asian | 6 participants | 10 participants | 16 participants |
| Race/Ethnicity, Customized Black | 21 participants | 25 participants | 46 participants |
| Race/Ethnicity, Customized Other | 10 participants | 10 participants | 20 participants |
| Race/Ethnicity, Customized White | 266 participants | 260 participants | 526 participants |
| Sex: Female, Male Female | 123 Participants | 119 Participants | 242 Participants |
| Sex: Female, Male Male | 180 Participants | 186 Participants | 366 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 135 / 303 | 121 / 305 |
| serious Total, serious adverse events | 27 / 303 | 33 / 305 |
Outcome results
Primary
Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score
The rate of aortic root enlargement, expressed as the annual change in the maximum aortic-root-diameter z score indexed to body-surface area over a 3-year period following randomization
Time frame: Up to 3 years following randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score | -0.139 z-score/year | Standard Error 0.013 |
| Losartan | Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score | -0.107 z-score/year | Standard Error 0.013 |
p-value: 0.08Mixed Models Analysis
Secondary
Adverse Drug Reactions Reported at the Baseline Visit
Time frame: At baseline
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Dizziness with standing, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Upper respiratory/Nasal congestion, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Fatigue, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Cough, any severity | 47 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Dizziness - other, any severity | 25 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Cough, bothersome | 1 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Behavior changes, bothersome | 2 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Dysgeusia, any severity | 10 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Dizziness - other, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Dysgeusia, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Headache, any severity | 112 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Stomach pain/Indigestion, any severity | 47 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Fainting with loss of consciousness, any severity | 5 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Stomach pain/Indigestion, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Insomnia, any severity | 60 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Nausea, any severity | 30 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Fainting with loss of consciousness, bothersome | 5 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Nausea, bothersome | 1 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Mood alterations, any severity | 54 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Vomiting, any severity | 23 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Palpitations, any severity | 60 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Vomiting, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Insomnia, bothersome | 2 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Diarrhea, any severity | 35 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Palpitations, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Diarrhea, bothersome | 1 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Fatigue, any severity | 84 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Constipation, any severity | 44 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Chest pain, any severity | 54 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Constipation, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Nightmares, any severity | 52 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Vascular (hands, feet), any severity | 35 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Chest pain, bothersome | 1 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Vascular (hands, feet), bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Mood alterations, bothersome | 7 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Muscle pain or Cramps, any severity | 59 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Dyspnea, any severity | 43 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Muscle pain or Cramps, bothersome | 2 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Nightmares, bothersome | 2 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Back pain, any severity | 60 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Dyspnea, bothersome | 3 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Back pain, bothersome | 3 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Headache, bothersome | 10 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Periorbital edema, any severity | 13 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Periorbital edema, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Wheezing, any severity | 15 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Pedal edema, any severity | 2 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Dizziness with standing, any severity | 60 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Pedal edema, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Wheezing, bothersome | 2 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Other, any severity | 21 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Behavior changes, any severity | 21 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Other, bothersome | 3 participants |
| Atenolol | Adverse Drug Reactions Reported at the Baseline Visit | Upper respiratory/Nasal congestion, any severity | 106 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Other, bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Headache, any severity | 114 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Headache, bothersome | 10 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Fatigue, any severity | 105 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Fatigue, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Mood alterations, any severity | 49 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Mood alterations, bothersome | 3 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Behavior changes, any severity | 23 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Behavior changes, bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Insomnia, any severity | 61 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Insomnia, bothersome | 2 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Nightmares, any severity | 53 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Nightmares, bothersome | 3 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Dizziness with standing, any severity | 58 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Dizziness with standing, bothersome | 2 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Dizziness - other, any severity | 27 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Dizziness - other, bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Fainting with loss of consciousness, any severity | 9 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Fainting with loss of consciousness, bothersome | 9 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Palpitations, any severity | 53 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Palpitations, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Chest pain, any severity | 58 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Chest pain, bothersome | 5 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Dyspnea, any severity | 38 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Dyspnea, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Wheezing, any severity | 14 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Wheezing, bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Upper respiratory/Nasal congestion, any severity | 117 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Upper respiratory/Nasal congestion, bothersome | 2 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Cough, any severity | 59 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Cough, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Dysgeusia, any severity | 3 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Dysgeusia, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Stomach pain/Indigestion, any severity | 61 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Stomach pain/Indigestion, bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Nausea, any severity | 35 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Nausea, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Vomiting, any severity | 23 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Vomiting, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Diarrhea, any severity | 43 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Diarrhea, bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Constipation, any severity | 35 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Constipation, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Vascular (hands, feet), any severity | 34 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Vascular (hands, feet), bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Muscle pain or Cramps, any severity | 58 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Muscle pain or Cramps, bothersome | 4 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Back pain, any severity | 67 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Back pain, bothersome | 2 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Periorbital edema, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Pedal edema, any severity | 3 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Pedal edema, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Other, any severity | 16 participants |
| Losartan | Adverse Drug Reactions Reported at the Baseline Visit | Periorbital edema, any severity | 15 participants |
Secondary
Adverse Drug Reactions Reported During Routine Follow-up Surveillance
Time frame: From 6 months to 3 years following randomization.
Population: All subjects who had any of the follow-up visits after 6 months post-randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Wheezing, any severity | 36 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Other, bothersome | 10 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Wheezing, bothersome | 2 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Insomnia, any severity | 108 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Upper respiratory/Nasal congestion, any severity | 188 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Headache, bothersome | 27 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Upper respiratory/Nasal congestion, bothersome | 3 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Insomnia, bothersome | 6 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Cough, any severity | 117 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Pedal edema, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Cough, bothersome | 1 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Nightmares, any severity | 100 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dysgeusia, any severity | 29 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Fatigue, any severity | 152 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dysgeusia, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Nightmares, bothersome | 7 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Stomach pain/Indigestion, any severity | 119 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Fainting with loss of consciousness, bothersome | 21 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Stomach pain/Indigestion, bothersome | 2 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dizziness with standing, any severity | 119 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Nausea, any severity | 99 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Fatigue, bothersome | 7 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Nausea, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dizziness with standing, bothersome | 6 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Vomiting, any severity | 81 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Other, any severity | 105 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Vomiting, bothersome | 1 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dizziness - other, any severity | 60 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Diarrhea, any severity | 94 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Mood alterations, any severity | 89 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Diarrhea, bothersome | 1 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dizziness - other, bothersome | 2 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Constipation, any severity | 77 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Fainting with loss of consciousness, any severity | 21 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Constipation, bothersome | 1 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Palpitations, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Vascular (hands, feet), any severity | 73 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Mood alterations, bothersome | 13 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Vascular (hands, feet), bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Chest pain, any severity | 114 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Muscle pain or Cramps, any severity | 148 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Palpitations, any severity | 86 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Muscle pain or Cramps, bothersome | 6 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Chest pain, bothersome | 14 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Back pain, any severity | 137 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Behavior changes, any severity | 51 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Back pain, bothersome | 5 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dyspnea, any severity | 75 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Periorbital edema, any severity | 22 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Headache, any severity | 202 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Periorbital edema, bothersome | 0 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dyspnea, bothersome | 1 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Pedal edema, any severity | 6 participants |
| Atenolol | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Behavior changes, bothersome | 5 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Pedal edema, any severity | 5 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Fainting with loss of consciousness, any severity | 16 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Fainting with loss of consciousness, bothersome | 16 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Pedal edema, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Other, any severity | 108 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Other, bothersome | 12 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Headache, any severity | 208 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Headache, bothersome | 20 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Fatigue, any severity | 153 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Fatigue, bothersome | 5 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Mood alterations, any severity | 86 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Mood alterations, bothersome | 13 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Behavior changes, any severity | 46 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Behavior changes, bothersome | 8 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Insomnia, any severity | 107 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Insomnia, bothersome | 4 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Nightmares, any severity | 94 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Nightmares, bothersome | 4 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dizziness with standing, any severity | 105 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dizziness with standing, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dizziness - other, any severity | 61 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Palpitations, any severity | 101 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Palpitations, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Chest pain, any severity | 106 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Chest pain, bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dyspnea, any severity | 72 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dyspnea, bothersome | 3 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Wheezing, any severity | 32 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Wheezing, bothersome | 5 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Upper respiratory/Nasal congestion, any severity | 186 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Upper respiratory/Nasal congestion, bothersome | 3 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Cough, any severity | 113 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Cough, bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dysgeusia, any severity | 16 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dysgeusia, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Stomach pain/Indigestion, any severity | 121 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Stomach pain/Indigestion, bothersome | 8 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Nausea, any severity | 78 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Nausea, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Vomiting, any severity | 75 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Vomiting, bothersome | 2 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Diarrhea, any severity | 90 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Diarrhea, bothersome | 3 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Constipation, any severity | 66 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Constipation, bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Vascular (hands, feet), any severity | 66 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Vascular (hands, feet), bothersome | 0 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Muscle pain or Cramps, any severity | 124 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Muscle pain or Cramps, bothersome | 7 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Back pain, any severity | 134 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Back pain, bothersome | 8 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Periorbital edema, any severity | 27 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Periorbital edema, bothersome | 1 participants |
| Losartan | Adverse Drug Reactions Reported During Routine Follow-up Surveillance | Dizziness - other, bothersome | 0 participants |
Secondary
Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area
Time frame: Up to 3 years following randomization.
Population: All randomized participants whose aortic-annulus-diameter z scores were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area | -0.279 z-score/year | Standard Error 0.018 |
| Losartan | Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area | -0.175 z-score/year | Standard Error 0.018 |
p-value: <0.001Mixed Models Analysis
Secondary
Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension
The rate of change in the absolute dimension of the aortic root over a 3-year period following randomization
Time frame: Up to 3 years following randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension | 0.069 cm/year | Standard Error 0.004 |
| Losartan | Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension | 0.075 cm/year | Standard Error 0.004 |
p-value: 0.2Mixed Models Analysis
Secondary
Annual Rate of Change in Arm Span to Height Ratio
Time frame: Up to 3 years following randomization.
Population: All randomized participants whose arm span to height ratios were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Arm Span to Height Ratio | 0.001 1/year | Standard Error 0.001 |
| Losartan | Annual Rate of Change in Arm Span to Height Ratio | 0.001 1/year | Standard Error 0.001 |
p-value: 0.49Mixed Models Analysis
Secondary
Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area.
Time frame: Up to 3 years following randomization.
Population: All randomized participants whose ascending-aorta-diameter z scores were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area. | -0.140 z-score/year | Standard Error 0.013 |
| Losartan | Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area. | -0.114 z-score/year | Standard Error 0.013 |
p-value: 0.15Mixed Models Analysis
Secondary
Annual Rate of Change in Body Mass Index
Time frame: Up to 3 years following randomization.
Population: All randomized participants whose body mass indexes were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Body Mass Index | 0.063 kg/m^2 per year | Standard Error 0.044 |
| Losartan | Annual Rate of Change in Body Mass Index | 0.076 kg/m^2 per year | Standard Error 0.044 |
p-value: 0.82Mixed Models Analysis
Secondary
Annual Rate of Change in Body Mass Index for Age Z-score
Time frame: Up to 3 years following randomization.
Population: All randomized participants who were between 0-20 years of age and whose body mass index for age z-scores were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Body Mass Index for Age Z-score | 0.007 z-score/year | Standard Error 0.022 |
| Losartan | Annual Rate of Change in Body Mass Index for Age Z-score | 0.021 z-score/year | Standard Error 0.022 |
p-value: 0.64Mixed Models Analysis
Secondary
Annual Rate of Change in Height
Time frame: Up to 3 years following randomization.
Population: All randomized participants whose heights were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Height | 0.822 cm/year | Standard Error 0.204 |
| Losartan | Annual Rate of Change in Height | 0.935 cm/year | Standard Error 0.202 |
p-value: 0.65Mixed Models Analysis
Secondary
Annual Rate of Change in Height-for-age Z-score
Time frame: Up to 3 years following randomization.
Population: All randomized participants who were between 0-20 years of age and whose heights were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Height-for-age Z-score | 0.046 z-score/year | Standard Error 0.013 |
| Losartan | Annual Rate of Change in Height-for-age Z-score | 0.019 z-score/year | Standard Error 0.013 |
p-value: 0.13Mixed Models Analysis
Secondary
Annual Rate of Change in the Absolute Diameter of the Aortic Annulus
Time frame: Up to 3 years following randomization.
Population: All randomized participants whose absolute dimensions of the aortic annulus were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in the Absolute Diameter of the Aortic Annulus | 0.015 cm/year | Standard Error 0.003 |
| Losartan | Annual Rate of Change in the Absolute Diameter of the Aortic Annulus | 0.030 cm/year | Standard Error 0.003 |
p-value: 0.002Mixed Models Analysis
Secondary
Annual Rate of Change in the Absolute Diameter of the Ascending Aorta
Time frame: Up to 3 years following randomization.
Population: All randomized participants whose absolute dimensions of the ascending aorta were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in the Absolute Diameter of the Ascending Aorta | 0.039 cm/year | Standard Error 0.004 |
| Losartan | Annual Rate of Change in the Absolute Diameter of the Ascending Aorta | 0.044 cm/year | Standard Error 0.004 |
p-value: 0.3Mixed Models Analysis
Secondary
Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area
Time frame: Up to 3 years following randomization.
Population: All randomized participants whose total aortic proximal regurgitant jet area indexes were measured at baseline or at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area | 0.005 (mm^2/m^2)/year | Standard Error 0.003 |
| Losartan | Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area | 0.001 (mm^2/m^2)/year | Standard Error 0.003 |
p-value: 0.29Mixed Models Analysis
Secondary
Annual Rate of Change in Upper to Lower Segment Ratio
Time frame: Up to 3 years following randomization.
Population: All randomized participants whose upper to lower segment ratios were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Upper to Lower Segment Ratio | -0.014 1/year | Standard Error 0.002 |
| Losartan | Annual Rate of Change in Upper to Lower Segment Ratio | -0.015 1/year | Standard Error 0.002 |
p-value: 0.59Mixed Models Analysis
Secondary
Annual Rate of Change in Weight
Time frame: Up to 3 years following randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Weight | 0.239 kg/year | Standard Error 0.153 |
| Losartan | Annual Rate of Change in Weight | 0.229 kg/year | Standard Error 0.154 |
p-value: 0.96Mixed Models Analysis
Secondary
Annual Rate of Change in Weight-for-age Z-score
Time frame: Up to 3 years following randomization.
Population: All randomized participants who were between 0-20 years of age and whose weight-for-age z-scores were measured at baseline and at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Weight-for-age Z-score | 0.011 z-score/year | Standard Error 0.013 |
| Losartan | Annual Rate of Change in Weight-for-age Z-score | 0.019 z-score/year | Standard Error 0.013 |
p-value: 0.45Mixed Models Analysis
Secondary
Annual Rate of Change in Weight-for-height Z-score
Time frame: Up to 3 years following randomization.
Population: All randomized participants who were \<120 cm in heights and whose weight-for-height z-scores were measured at baseline or at any of the follow-up visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atenolol | Annual Rate of Change in Weight-for-height Z-score | -0.001 z-score/year | Standard Error 0.072 |
| Losartan | Annual Rate of Change in Weight-for-height Z-score | -0.157 z-score/year | Standard Error 0.076 |
p-value: 0.13Mixed Models Analysis
Secondary
Event Rate of Aortic Dissection.
Percentage of participants who had aortic dissection over a 3-year period following randomization.
Time frame: Up to 3 years following randomization.
Population: All randomized participants who received the treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atenolol | Event Rate of Aortic Dissection. | 0 Percentage of participants |
| Losartan | Event Rate of Aortic Dissection. | 0.7 Percentage of participants |
p-value: 0.16Log Rank
Secondary
Event Rate of Aortic-Root Surgery
Percentage of participants who had aortic-root surgery over a 3-year period following randomization.
Time frame: Up to 3 years following randomization.
Population: All randomized participants who received the treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atenolol | Event Rate of Aortic-Root Surgery | 3.4 Percentage of participants |
| Losartan | Event Rate of Aortic-Root Surgery | 6.0 Percentage of participants |
p-value: 0.13Log Rank
Secondary
Event Rate of Death
Percentage of participants who died over a 3-year period following randomization.
Time frame: Up to 3 years following randomization.
Population: All randomized participants who received the treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atenolol | Event Rate of Death | 0 Percentage of participants |
| Losartan | Event Rate of Death | 0.3 Percentage of participants |
p-value: 0.32Log Rank
Secondary
Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.
Percentage of participants who had aortic dissection, aortic-root surgery or death over a 3-year period following randomization
Time frame: Up to 3 years following randomization.
Population: All randomized participants who received the treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atenolol | Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death. | 3.4 Percentage of participants |
| Losartan | Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death. | 6.4 Percentage of participants |
p-value: 0.1Log Rank
Secondary
Number of Death.
Time frame: Up to 3 years following randomization.
Population: All randomized participants who received the treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atenolol | Number of Death. | 0 participants |
| Losartan | Number of Death. | 1 participants |
Secondary
Number of Participants With Aortic Dissection.
Time frame: Up to 3 years following randomization.
Population: All randomized participants who received the treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atenolol | Number of Participants With Aortic Dissection. | 0 participants |
| Losartan | Number of Participants With Aortic Dissection. | 2 participants |
Secondary
Number of Participants With Aortic-root Surgery.
Time frame: Up to 3 years following randomization.
Population: All randomized participants who received the treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atenolol | Number of Participants With Aortic-root Surgery. | 10 participants |
| Losartan | Number of Participants With Aortic-root Surgery. | 18 participants |
Secondary
Number of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.
Time frame: Up to 3 years following randomization.
Population: All randomized participants who received the treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atenolol | Number of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death. | 10 participants |
| Losartan | Number of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death. | 19 participants |