Brief Title
Effect of Bisoprolol on Progression of Aortic Stenosis
Official Title
A Randomized Trial of Beta-blocker Therapy in Aortic Stenosis
Brief Summary
Aortic stenosis has been thought to be a degenerative process basically induced by
long-lasting mechanical stress, and hemodynamic factors such as shear forces, acceleration of
blood flow, hypertension and rapid heart rate might contribute to progression of aortic
stenosis. Peak aortic jet velocity is known to be associated with clinical outcomes in mild
and moderate AS, and our previous study showed that rate of progression was significantly
associated with baseline aortic jet velocity in mild aortic stenosis. Because beta-blocker
therapy would decrease aortic jet velocity and heart rate, it might decrease hemodynamic
stress and eventually slow down the degenerative process in patients whose disease is not too
advanced for therapy to be effective. The investigators hypothesized that a beta-blocker
therapy would decrease the rate of progression of aortic stenosis by modifying hemodynamic
factors favorably in patients with mild to moderate aortic stenosis.
Detailed Description
Aortic stenosis (AS) is a gradually progressive disease, characterized by an increase in
calcium deposition leading to progressive narrowing of the aortic valve (AV). There are
currently no effective medical treatment to halt the disease process and surgical valve
replacement remains the only proven therapy when the valve becomes severely stenotic. AS is
mediated by a chronic inflammatory disease process, very similar to that seen in
atherosclerosis, but lipid-lowering therapy did not slow the progression of AS in the
SALTIRE, SEAS, or ASTRONOMER trials. It is possible that these trials may have targeted
patients in whom disease was too advanced for lipid-lowering therapy to be effective, or in
whom atherosclerotic mechanism was not the central pathogenic process in AS. Because
identifying and treating patients in earlier stages of AS would not be cost-effective, it
seems more logical to explore alternative pharmacological approaches.
AS has been thought to be a degenerative process basically induced by long-lasting mechanical
stress, and hemodynamic factors such as shear forces, acceleration of blood flow,
hypertension and rapid heart rate might contribute to progression of AS. Peak aortic jet
velocity is known to be associated with clinical outcomes in mild and moderate AS, and our
previous study showed that rate of progression was significantly associated with baseline
aortic jet velocity in mild AS. Because beta-blocker therapy would decrease aortic jet
velocity and heart rate, it might decrease hemodynamic stress and eventually slow down the
degenerative process in patients whose disease is not too advanced for therapy to be
effective. In a retrospective, observational study, beta-blocker therapy was associated with
a favorable clinical outcome in AS.
The investigators hypothesized that bisoprolol, a new generation beta-blocker, would decrease
the rate of progression of AS by modifying hemodynamic factors favorably in patients with
mild to moderate AS.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Change in peak aortic jet velocity from baseline to 4 years follow-up
Secondary Outcome
Change in mean pressure gradient across aortic valve
Condition
Aortic Stenosis
Intervention
bisoprolol
Study Arms / Comparison Groups
bisoprolol
Description: bisoprolol 5mg qd
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
July 2012
Completion Date
May 2014
Primary Completion Date
May 2014
Eligibility Criteria
Inclusion Criteria:
- Mild to moderate aortic stenosis defined by peak velocity of aortic jet between 2.0
and 3.5 m/sec
- Untreated hypertension: systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg Treated
hypertension using dihydropiridine calcium channel blockers, ACE inhibitors, ARB or
diuretics
- Patients received no beta-blocker therapy for more than 12 months
Exclusion Criteria:
- Symtomatic aortic stenosis: presence of exertional dyspnea, angina or syncope
- Planned cardiac surgery (e.g., CABG, valve repair or replacement, or aneurysmectomy)
or planned major non-cardiac surgery within the study period
- Stroke or resuscitated sudden death in the past 6 months
- Evidence of congestive heart failure, or left ventricular ejection fraction < 50%
- Significant renal disease manifested by serum creatinine > 2.0mg/dL
- History of intolerance to beta-blocker
- History of adult asthma manifested by bronchospasm in the past 6 months, or currently
taking regular anti-asthmatic medication(s)
- Moderate or severe aortic regurgitation
- Atrial fibrillation
- Female of child-bearing potential who do not use adequate contraception and women who
are pregnant or breast-feeding
- A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in
the past 3 years or current treatment for the active cancer
- Any clinically significant abnormality identified at the screening visit, physical
examination, laboratory tests, or electrocardiogram which, in the judgment of the
Investigator, would preclude safe completion of the study
- Unwillingness or inability to comply with the procedures described in this protocol
Gender
All
Ages
20 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Duk-Hyun Kang, M.D., ,
Location Countries
Korea, Republic of
Location Countries
Korea, Republic of
Administrative Informations
NCT ID
NCT01579058
Organization ID
2011-0884
Responsible Party
Principal Investigator
Study Sponsor
Asan Medical Center
Collaborators
Merck Sharp & Dohme Corp.
Study Sponsor
Duk-Hyun Kang, M.D., Principal Investigator, Asan Medical Center
Verification Date
June 2018