Aortic Valve Stenosis
Conditions
Keywords
calcific aortic valve stenosis, echocardiography, transthoracic
Brief summary
The purpose of this study is to find out if an approved medicine that is used to lower cholesterol called Lipitor can slow or stop progressive narrowing of the aortic heart valve in patients with a condition called aortic stenosis. Patients who have aortic stenosis who volunteer for this study will take Lipitor for 2 years and will undergo a brief exam by a physician, labwork to measure cholesterol, and a routine heart ultrasound (sound picture of the heart) at the start of the study and every 6 months, stopping at 2 years.
Detailed description
This is a prospective, single-center study assessing the effect of atorvastatin 40 mg/day (Lipitor, Pfizer) on the progression of calcific aortic stenosis in approximately 70 patients with mild to moderate calcific AS of a tricuspid or bicuspid aortic valve. As a control population, published data on historical AS cohorts will be used, employing the accepted rate of progression of a decrease in aortic valve area of 0.1 cm²/year. Additionally, also for comparison, we will prospectively study a registry of AS patients who meet our entry criteria but are either currently already being treated with or refuse to take an HMG-CoA reductase inhibitor (referred to as the standard care group). All patient visits, laboratory studies, and echocardiograms will be performed at the Cleveland Clinic Foundation in Cleveland, Ohio with the exception of the 12-week visit ALT measurement which may be done at the patient's local doctor's office and the results faxed to Imaging Research. The 12-week follow-up assessment may be completed over the phone to establish any change in patient status since baseline, study medication compliance, concomitant medication use and to ascertain whether or not the appropriate laboratory test was obtained. Over a 2-year period, assessments will be conducted at baseline, 6, 12, 18, and 24 months.
Interventions
atorvastatin 40 mg by mouth once daily
Sponsors
Pfizer
The Cleveland Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Mild to moderate calcific AS of a tricuspid or bicuspid aortic valve * Echocardiographic derived mean pressure gradient \>10 mmHg and an aortic valve area of 0.9 to 1.7 cm2 by continuity equation. * Laboratory evidence of LDL-c\>70 mg/dl within 12 months prior to recruitment.
Exclusion criteria
* Left ventricular ejection fraction \<50% * Valvular area of 0.9 cm2 and a mean gradient \>30 mmHg * Rheumatic heart disease * \>Moderate (2+) aortic insufficiency * Prior statin therapy to include: \>10 mg of atorvastatin (Lipitor) or \>20 mg of other HMG-CoA Reductase Inhibitors (statins) * End-stage renal disease (ESRD) * History of thoracic radiation * Unable or unwilling to sign informed consent * Unable to unwilling to return for follow-up * Other clinically important renal, pulmonary, hepatic, neurological, endocrine, or hematological disorders, vasculitis, or any other situation or medical condition that, in the investigator's opinion, would make survival for the duration of the study unlikely, or would otherwise interfere with optimal participation in the study or produce a significant risk to the patient * Severe pulmonary hypertension (\>55 mmHg)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aortic Stenosis | 2 years | aortic valve area as measured by transthoracic echocardiography was not obtained due to poor reproducibility |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Change in the Aortic Valve Area Measured by Transthoracic Echocardiography Compared to That of Historical Controls | 2 years | Rate of change in the aortic valve area measured by transthoracic echocardiography compared to that of historical controls was not obtained. Primary outcome measurement was not obtainable, thus comparison to historic controls was not possible. |
| Rate of Change in the Aortic Valve Area Measured by TEE Compared to That of Historical Controls | 2 years | Poor reducibility of aortic valve area measurements with transthoracic echocardiography images resulted in primary measure not being obtained. As the outcome measurement was not obtained, comparison to historical controls was not possible. |
| Rate of Change in Aortic Valve Area as Measured by TEE Compared to Standard of Care Group | 2 years | Poor reducibility of aortic valve area measurements with transthoracic echocardiography images resulted in the primary outcome measure not being obtained. Thus, comparison to the stand of care group was not possible. |
| Change in Mean and Peak Gradients Across the Aortic Valve as Measured by TEE in the Treated Group Compared to Historical Control Group. | 2 years | Poor reducibility of aortic valve area measurements with transthoracic echocardiography images resulted in the primary outcome measure not being obtained. This secondary measurement was not obtained as it was deemed not relevant in the absence of the primary outcome measurement and other secondary outcome measurements. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AORTIC STENOSIS PATIENTS Patients with mild to moderate calcific aortic stenosis will receive atorvastatin 40 mg by mouth once daily
atorvastatin (Lipitor): atorvastatin 40 mg by mouth once daily | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Primary endpoint measure not obtainable | 59 |
Baseline characteristics
| Characteristic | AORTIC STENOSIS PATIENTS | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 8 Participants | — |
| Age, Categorical Between 18 and 65 years | 51 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 14 Participants | — |
| Sex: Female, Male Male | 45 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 59 |
| other Total, other adverse events | 0 / 59 |
| serious Total, serious adverse events | 0 / 59 |
Outcome results
Primary
Aortic Stenosis
aortic valve area as measured by transthoracic echocardiography was not obtained due to poor reproducibility
Time frame: 2 years
Population: Population had aortic stenosis, however the primary endpoint of Aortic Valve Area was not obtainable due to poor reproducibility. As a result, the study was terminated.
Secondary
Change in Mean and Peak Gradients Across the Aortic Valve as Measured by TEE in the Treated Group Compared to Historical Control Group.
Poor reducibility of aortic valve area measurements with transthoracic echocardiography images resulted in the primary outcome measure not being obtained. This secondary measurement was not obtained as it was deemed not relevant in the absence of the primary outcome measurement and other secondary outcome measurements.
Time frame: 2 years
Population: Poor reducibility of aortic valve area measurements with transthoracic echocardiography images resulted in the primary outcome measure not being obtained. This secondary measurement was not obtained as it was deemed not relevant in the absence of the primary outcome measurement and other secondary outcome measurements.
Secondary
Rate of Change in Aortic Valve Area as Measured by TEE Compared to Standard of Care Group
Poor reducibility of aortic valve area measurements with transthoracic echocardiography images resulted in the primary outcome measure not being obtained. Thus, comparison to the stand of care group was not possible.
Time frame: 2 years
Population: Poor reducibility of aortic valve area measurements with transthoracic echocardiography images resulted in the primary outcome measure not being obtained. Thus, comparison to the stand of care group was not possible.
Secondary
Rate of Change in the Aortic Valve Area Measured by TEE Compared to That of Historical Controls
Poor reducibility of aortic valve area measurements with transthoracic echocardiography images resulted in primary measure not being obtained. As the outcome measurement was not obtained, comparison to historical controls was not possible.
Time frame: 2 years
Population: Poor reducibility of aortic valve area measurements with transthoracic echocardiography images resulted in primary measure not being obtained. As the outcome measurement was not obtained, comparison to historical controls was not possible.
Secondary
Rate of Change in the Aortic Valve Area Measured by Transthoracic Echocardiography Compared to That of Historical Controls
Rate of change in the aortic valve area measured by transthoracic echocardiography compared to that of historical controls was not obtained. Primary outcome measurement was not obtainable, thus comparison to historic controls was not possible.
Time frame: 2 years
Population: Primary outcome measurement was not obtainable, thus comparison to historic controls was not possible.