Aortic Valve Stenosis, Heart Failure, Hypertension,Essential
Conditions
Keywords
Aortic Valve Stenosis, Hypertension, Heart failure
Brief summary
The aim of this study is to investigate the effect of strict blood pressure control versus conventional care in patients with asymptomatic moderate to severe aortic valve stenosis. The study is a randomized (1:1), open label, controlled intervention trial. Hypothesis: 1. Strict BP control for 12 months reduces the progression of LV remodelling compared to conventional treatment. 2. Strict BP control for 2 years reduces the increase in aortic valve calcification and LV remodelling compared to conventional treatment. 3. Strict BP reduction for up to 10 years reduces the need for aortic valve replacement and cardiovascular events compared to conventional care.
Interventions
OTHERBlood presssure reduction
Patients will be uptitrated in antihypertensive treatment until the treatment target is achieved.
Sponsors
Henrik Wiggers
Danish Heart Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
1\. BP-AVALVE I: 60 patients will be randomized (1:1) to either strict BP control (N=30) or conventional treatment (N=30). Treatment period will be 12 months. 2\. BP-AVALVE II: 200 patients will be randomized (1:1) to either strict BP control as in study 1 (N=100) or conventional care as in study 1 (N=100). Average treatment period will be 2 (1-3) years. 3\. BP-AVALVE III: Patients from BP-AVALVE-II continue in the randomized design until they develop symptoms of AS or have been followed for 10 (7-13) years. Patients will be reexamined at the end of the study period or in case they develop symptoms or LV failure and thus indication of valve replacement. Since the medicinal products used in this study is not the subject of the trial, the Danish Medicines Agency has classified this study as a clinical trial, in which medicinal products are used as a tool to induce a well-known physiological response. Therefor no further approval from the Danish Medicine Agency is required.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aortic valve peak velocity (Vmax) of 3.0-5.0 m/s and/or aortic valve area (AVA) ≤ 1.2 cm2 * Blood pressure: SBP \>= 127 mmHg measured by BP-TRU * LVEF ≥ 50% * Age \> 18 years * Safe birth control management (intrauterine devices or hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)) for women of childbearing potential. * Negative urine-HCG for women of childbearing potential * Ability to understand the written patient information and to give informed consent.
Exclusion criteria
* Symptoms due to AS * Symptomatic orthostatic hypotension and/or one minute standing SBP \< 110 mmHg (16). * Suspicion of secondary hypertension * Participation in other randomized drug study (device studies accepted) * Moderat to severe aortic valve regurgitation e.g. vena contracta \> 5 mm, assessed by echocardiography) * Known or suspected ischemic heart disease (coronary angiography with \>70% stenosis in a major epicardial vessel, symptoms or signs of myocardial ischemia, e.g. angina pectoris, wall motion abnormalities). Patients who have previously undergone complete revascularization of major coronary arteries due to angina pectoris are eligible for inclusion. * Significant coronary obstructive lesions detected by baseline Cardiac CT that requires a revascularisation procedure. * eGFR \< 30 ml/min or end-stage renal disease * Other disease, comorbidity or treatment making the subject unsuitable for study participation as judged by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in LV mass | Changes will be evaluated after an expected average of 12 months treatment | LV mass as measured by cardiac MR |
| Change in aortic valve CT calcium volume and aortic peak gradient | Changes will be evaluated after an expected average of 2-3 years treatment | Cardiac CT and Echocardiography |
| Clinical composite endpoint: | Will be evaluated after an expected average of 7-13 years of treatment | Major cardiovascular events including death from cardiovascular causes, aortic valve replacement, non-fatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary artery bypass surgery, percutaneous coronary intervention, and haemorrhagic and non-haemorrhagic stroke, new onset atrial fibrillation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LV mass-cavity ratio. | Through study completion, an average of 1 year | Cardiac MR |
| LV myocardial fibrosis | Through study completion, an average of 1 year | Cardiac MR |
| Myocardial perfusion during rest and stress | Through study completion, an average of 1 year | Cardiac MR |
| Aortic peak and mean gradients | Through study completion, an average of 1 year | Echocardiography |
| Aortic valve area | Through study completion, an average of 1 year | Echocardiography |
| Left ventricular global longitudinal strain | Through study completion, an average of 1 year | Echocardiography |
| Valvolu-arterial impedance | Through study completion, an average of 1 year | Echocardiography |
| NT-proBNP | Baseline and follow-up | Blood test |
| Minnesota living with heart failure questionnaire | Through study completion, an average of 1 year | Questionnaire |
| Ambulatory 24-hour blood pressure measurement | Through study completion, an average of 1 year | Ambulatory 24-hour blood pressure measurement |
| Dimensions and aortic calcium score of the thoracic aorta. | Through study completion, an average of 2 years | cardiac CT |
Countries
Denmark
Contacts
PRINCIPAL_INVESTIGATORHenrik Wiggers
Aarhus University Hospital, Department of Cardiology
Outcome results
None listed