Coarctation of the Aorta
Conditions
Keywords
Coarctation of the aorta, cross over design, atorvastatin, endothelial function
Brief summary
Coarctation of the aorta (CoA) accounts for approximately 8% of all congenital heart problems. Patients with CoA are well known to have an increased rates of early heart disease, high blood pressure, heart failure and stroke. Abnormal arterial function (dilation and constriction of the blood vessels) has been observed in these patients and likely contributes to the increased risk of cardiovascular problems. However, therapies targeted at improving arterial function have not been investigated in this population. Statin therapy (cholesterol medicines like Lipitor) have been studied in other subgroups of patients with abnormal arterial function and has shown benefit in improving arterial function and reducing risk of cardiovascular problems. The investigators hypothesize that patients with CoA have abnormal arterial function leading to increased cardiovascular risk. We further hypothesize that statin therapy may improve this problem. We plan to compile a complete database of information regarding these patients cardiovascular health and propose to then examine the effect of atorvastatin (Lipitor) on arterial function as measured by changes in arm arterial function tests.
Detailed description
The study design is a randomized double-blind cross over clinical trial. Patients who meet inclusion criteria and no exclusion criteria will be enrolled. They will undergo a baseline cardiovascular assessment including echocardiography, magnetic resonance imaging or magnetic resonance angiography (MRI/MRA), serum blood samples, brachial artery reactivity testing, and carotid intimal media thickness testing. Once they have completed their baseline testing, they will be randomized to either atorvastatin 80mg or placebo. They will complete 12 weeks of therapy and return at the end of 12 weeks to have a repeat brachial artery study and serum studies. There will then be a four week washout period where they take no medication. They will return for a follow up visit at the end of that four week period for repeat baseline brachial artery testing and serum studies. They then will be assigned to the opposite agent they were on previously (so if they originally were on placebo they switch to atorvastatin and vice versa). They will complete another 12 weeks of therapy and return at the end for a final brachial artery study and blood testing.
Interventions
DRUGatorvastatin
Atorvastatin 80mg daily vs. placebo daily X 12 weeks, then 4 week washout period, then cross over groups to complete another 12 weeks. (Total study time is 28 weeks (12+4+12)
DRUGSugar pill
atorvastatin 80mg daily vs. placebo daily X 12 weeks, then 4 week washout, then cross over groups X 12 weeks. Total study time is 28weeks (12+4+12).
Sponsors
American Heart Association
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients over the age of 18 years with repaired coarctation of the aorta (CoA) and willing to participate in all portions of the study including follow up, blood draws, urine sample, echocardiogram, MRI, brachial artery flow-mediated dilatation (FMD) testing, Carotid Intima Media Thickness (CIMT) testing and statin administration.
Exclusion criteria
* patients who are pregnant, nursing, or planning on becoming pregnant in the subsequent year * current smokers * patients with documented coronary artery disease (CAD), other systemic inflammatory disorder such as systemic lupus erythematosis or rheumatoid arthritis * patients already on statin therapy or who have had previous adverse effects to statin therapy * patients with hepatic transaminases \>2X the upper limit of normal * patients with creatinine clearance \<60mg/dL * patients who have implanted devices such as pacemakers or defibrillators that preclude MRI testing * patients with low blood pressure at baseline (\< 90/50) * patients who are unwilling or unable to comply with the aforementioned portions of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-post Change in Brachial Artery Reactivity | Baseline, 12 weeks | Brachial artery reactivity was assessed by Flow-mediated dilatation (FMD), performed before and after the 12 week period on therapy. FMD uses high-frequency ultrasound measurement of changes in brachial artery diameter after a 5-minute blood pressure cuff arterial occlusion. Brachial artery reactivity has been shown to predict long-term cardiovascular events. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the UCSF Adult Congenital Heart Disease Clinic between July 2008 and July 2009. All reviewed the study protocol and agreed to participate. There was no compensation for study participants.
Pre-assignment details
Patients were excluded if they did not have prior repair of aortic coarctation or could not participate in all 4 study visits.
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin Then Sugar Pill, or Sugar Pill Then Atorvastatin Patients were randomly assigned to receive atorvastatin or placebo once daily for 12 weeks. After a 4 week washout, each participant received the other intervention for 12 weeks. Brachial artery assessment were performed before and after each 12 week intervention. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Atorvastatin Then Sugar Pill, or Sugar Pill Then Atorvastatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age Continuous | 35 years STANDARD_DEVIATION 8.8 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Pre-post Change in Brachial Artery Reactivity
Brachial artery reactivity was assessed by Flow-mediated dilatation (FMD), performed before and after the 12 week period on therapy. FMD uses high-frequency ultrasound measurement of changes in brachial artery diameter after a 5-minute blood pressure cuff arterial occlusion. Brachial artery reactivity has been shown to predict long-term cardiovascular events.
Time frame: Baseline, 12 weeks
Population: 12 enrolled participants were randomly assigned to receive a 12-week course of either atorvastatin or placebo, followed by a 4-week washout, then 12 weeks on the alternate intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Pre-post Change in Brachial Artery Reactivity | 3 mm | Standard Deviation 1.5 |
| Sugar Pill | Pre-post Change in Brachial Artery Reactivity | 3 mm | Standard Deviation 1.5 |
Comparison: Null hypothesis: pre-post brachial artery diameter changes do not differ between placebo and atorvastatinp-value: >0.05t-test, 2 sided