Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)
Condition: Cardiac Disease
MeSH terms: Heart Diseases; Aortic Valve Disease; Bicuspid Aortic Valve Disease
Intervention: Atenolol; Telmisartan
Intervention description: Atenolol or matching placebo 25 mg up-titrated to 100 mg; Telmisartan or matching placebo 40 mg up-titrated to 80mg.
Intervention MeSH terms: Atenolol; Telmisartan
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Congenital; Aortic Valve; Bicuspid; Aortopathy; bicuspid aortic valve aortopathy

Summary:

      The purpose of this study is to determine whether long-term treatment with a beta-blocker
      (BB) such as atenolol and/or an angiotensin receptor blocker (ARB) such as telmisartan, given
      to adult patients with bicuspid aortic valve (BAV) disease (aortopathy) reduces the widening
      (dilatation) of the aorta from its baseline size.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age => 18 years

          -  Men and women with BAV and ascending aorta measuring > 37mm.

          -  Written informed consent

        General Study Exclusion Criteria

          1. History of cardiac diseases, such as

               -  Symptomatic aortic stenosis or aortic regurgitation referred for surgical
                  intervention or asymptomatic severe aortic stenosis or regurgitation based on
                  current guidelines

               -  Uncontrolled heart failure, right ventricular failure due to pulmonary
                  hypertension

               -  Cardiogenic shock

          2. Systolic blood pressure < 100 mmHg

          3. History of drug sensitivity, contraindication or adverse reaction to both BB and ARB.
             Participants who are able to tolerate only a BB will be allocated to the BB vs.
             placebo arm, and participants who are able to tolerate only an ARB will be allocated
             to the ARB vs. placebo arm, assuming no other exclusion criteria are met.

          4. Ascending aorta measuring ≥ 50mm, requiring prophylactic ascending aorta surgery

          5. Unable to provide informed consent

          6. Need for both BB and ARB for treatment of concomitant medical conditions for which
             there are no other alternatives. Participants who are taking an ARB which cannot be
             discontinued will be allocated to the BB arm, and participants who are taking a BB
             which cannot be discontinued will be allocated to the ARB arm, if no other exclusion
             criteria are met.

          7. Prior surgery on ascending aorta or aortic root (balloon valvuloplasty, aortic
             valvotomy or post coarctation surgery are acceptable)

          8. Women who are pregnant at screening visit

          9. Contraindication to MRI (claustrophobia, pacemaker, metallic clip in eye or brain)

         10. History of any illness which limits the participants' ability to complete the study

        Additional Exclusion Criteria for BB arm only

          1. Heart rate <60 bpm

          2. Heart block (1st, 2nd and 3rd degree AV block on ECG), or sick sinus syndrome

          3. Asthma of sufficient severity to represent a contraindication to BB use in the
             judgment of the patient's physician

          4. History of severe peripheral artery disorders

          5. History of pheochromocytoma without the use of alpha-adrenergic blockers

          6. History of metabolic acidosis

        Additional Exclusion Criteria for ARB arm only

          1. Women who are pregnant, lactating or who intend to become pregnant during the course
             of the study

          2. Women who are of childbearing age and are not on reliable, accepted form of birth
             control

          3. Hyperkalemia [serum potassium > 5.5 mmol/L] or renal dysfunction [GFR<45% measured by
             MDRD)

          4. Patients being treated with an ACE Inhibitor that cannot be discontinued. (These
             patients may be randomized in the BB arm if no exclusion criteria are met.)

          5. History of bilateral renal artery stenosis or unilateral renal artery stenosis to a
             solitary kidney

          6. History of hepatic insufficiency and hepato-biliary obstruction

          7. History of fructose intolerance