Critical Stenosis of Aortic Valve Clinical Trial
Official title:
Safety and Efficacy of Angiotensin Receptor Blocker, Fimasartan, on Patients With Aortic Stenosis
We hypothesized that fimasartan, a new generation ARBs, would improve exercise capacity and decrease the rate of progression of AS by modifying hemodynamic factors and reducing adverse LV remodeling favorably in patients with asymptomatic moderate to severe AS.
Aortic stenosis (AS) is common valvular disorder, affecting 2% to 4% of adults older than 65
years. It is gradually but constantly progressive disease whit a long asymptomatic phase,
but once symptoms develop, the prognosis is poor.
Currently, treatment strategy is focused mainly to watchful monitoring and judicious timing
of aortic valve replacement (AVR). However, not all patients are proper candidate of
corrective surgery and the needs of development of medical treatment are increasing. Various
mechanisms have been suggested in progression of AS and recent observational studies
suggested not only mechanical stress of "wear and tear" but also active inflammatory process
likewise atherosclerosis may contribute the progression of AS. Through clinical descriptive
studies, atherosclerotic risk factors, such as hypertension, diabetes mellitus,
dyslipidemia, obesity, smoking, and metabolic syndrome have been known to facilitate the
progression of AS.
The renin-angiotensin system (RAS) is activated at an early stage of AS, promoting
developemtnt of left ventricular hypertrophy (LVH), myocardial fibrosis, and diastolic
dysfunction. Lipid lowering therapy and RAS blockade have emerged potential medical
treatment to slow the progression of AS, however, many clinical trials did not show
consistent beneficial effect of statins.8-10 RAS blockers are perceived as being relative
contraindication due to concerns about increasing pressure gradient. However, patients with
AS tolerate RAS blocker well on initiation and the use of angiotensin converting enzyme
(ACE) inhibitors appears to confer long term survival benefit on patients considered to have
a contraindication including AS.Pressure overload of LV, activation of RAS, and subsequent
adverse LV remodeling, myocardial fibrosis, and LV dysfunction may potential therapeutic
target to retard the progression of AS and to improve exercise capacity, and even long-term
outcomes. RAS blocker including ACEI or angiotensin receptor blockers (ARBs) have been known
to improve exercise capacity and long term outcome in patient with hypertension, congestive
heart failure, or myocardial infarction.
We hypothesized that fimasartan, a new generation ARBs, would improve exercise capacity and
decrease the rate of progression of AS by modifying hemodynamic factors and reducing adverse
LV remodeling favorably in patients with asymptomatic moderate to severe AS.
Prospective, double-blinded, randomized clinical trial with enrollment of normotensive or
hypertensive patients of age 20 to 75 who require echocardiography for a clinical
indication, which typically consists of known aortic stenosis or presence of cardiac murmur.
Moderate to severe aortic stenosis will be defined as a continuous wave Doppler determined
peak aortic valve jet velocity of 3.0 - 4.5 m/s or mean pressure gradient of 25 - 49 mmHg,
or aortic valve area of 0.76 - 1.5 cm2. Patients meeting inclusion criteria without any
exclusion criteria will be randomized 1:1 to angiotensin receptor blocker, Fimasartan, or
placebo. After 1-year enrollment period, all patients will be followed for 1 year.
Cardiopulmonary exercise test will be performed at baseline enrollment period, and at the
end of follow-up. Echocardiographic evaluation will be performed at regular interval of
baseline and 6 months interval until the end of study.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment