None listed
Conditions
Brief summary
Due to a progressive build-up of calcium, aortic stenosis (AS) restricts movement of the valve leaflets, increasing the workload of the heart. Over time this causes scarring and reduces the ability of the heart to function, and without treatment leads to heart failure and death. Currently there are no medications to slow the progression of AS and treatment is based on careful observation to time heart valve replacement, which is an expensive and sometimes risky procedure. High blood pressure is associated with more rapid progression of AS and scarring of the heart muscle. It is unknown whether lowering blood pressure changes outcomes related to aortic valve disease. Even after aortic valve replacement, scar tissue remains and can increase the risk of heart failure and death. This study aims to analyse the efficacy of medications to reduce the workload on the heart, starting when AS is in a mild to moderate stage. We will examine the progression of AS and changes in the heart muscle over time, to see if reducing the workload on the heart will slow the development and progression of problems related to AS.
Interventions
B: Intervention group
A combination of a beta-blocker (bisoprolol) plus angiotensin receptor blocker (candesartan) plus calcium channel blocker (amlodipine)
Bisoprolol doses - 2.5mg, 5mg, 10mg
Candesartan doses - 8mg, 16mg, 32mg
Amlodipine doses - 2.5mg, 5mg, 10mg
Dose titration will be performed as follows:
• Initially start 8mg candesartan per day.
• Week 2: as long as BP remains >100mmHg, add Bisoprolol 2.5mg daily.
• Week 3: as long as BP remains >100mmHg, add Amlodipine 2.5mg daily.
• Me
B: Intervention group A combination of a beta-blocker (bisoprolol) plus angiotensin receptor blocker (candesartan) plus calcium channel blocker (amlodipine) Bisoprolol doses - 2.5mg, 5mg, 10mg Candesartan doses - 8mg, 16mg, 32mg Amlodipine doses - 2.5mg, 5mg, 10mg Dose titration will be performed as follows: • Initially start 8mg candesartan per day. • Week 2: as long as BP remains >100mmHg, add Bisoprolol 2.5mg daily. • Week 3: as long as BP remains >100mmHg, add Amlodipine 2.5mg daily. • Medications will then be titrated in order each week - candesartan 16mg week 4/32mg week 7, bisoprolol 5mg week 5/10mg week 8, amlodipine 5mg week 6/10mg week 9 In case of intolerance to standard titration, a lower rate of dose escalation can be used. All drugs will be oral tablets given once daily over the length of the study (10 years), and may continue indefinitely following satisfactory evaluation. Adherence will be monitored by comparison with pharmaceutical dispensing and by questionnaire.
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
• Provide signed and dated informed consent form (analogue or digital). • Willing to comply with all study procedures and be available for the duration of the study. • Age between 18 and 90 years, inclusive. • Systolic BP <200 and >100 mmHg. • Participant has mild to moderate AS as defined by echocardiogram with; o aortic valve thickening/calcification and o maximum aortic valve transvalvular velocity 2.5 – 4.0 m/s and o mean aortic valve transvalvular gradient (AVG) <40mmHg and o Qualitative restriction to valve opening • Bicuspid or tricuspid aortic valve is eligible for inclusion.
Exclusion criteria
• Major medical comorbidities that, in the opinion of the investigator, would make initiation or adjustment of medications unsafe, or life expectancy is estimated to be less than 5 years. • Significantly impaired renal function (CKD4 or more significant, i.e. eGFR < 30ml/min/1.73m2). • Left ventricular ejection fraction < 50% • Pregnancy • Already prescribed maximal tolerated doses of any one of the investigational antihypertensive regimes (i.e. maximal tolerated dose of (beta-blocker and angiotensin receptor blocker) or (calcium channel blocker)) • Contraindication to any one of the investigational antihypertensive regimes (i.e. to both beta-blocker and angiotensin receptor blocker, or to calcium channel blocker) • Cognitive impairment, dementia, or other limitation that would make the study participant unable to follow dose escalation/study protocols.
Outcome results
None listed