Evaluation of The Effects of Nebivolol in Comparison to Atenolol on Wall Shear Stress and Rupture Prone Coronary Plaques
Condition: Atherosclerosis; Endothelial Function
MeSH terms: Atherosclerosis; Rupture
Study type: Interventional
Phase: Phase 4

Summary: 
      Nebivolol is a novel blood pressure lowering drug with an additional effect on the inner
      lining of blood vessels to release a compound called nitric oxide that can relax blood
      vessels. Atenolol is a blood pressure reducing agent without the ability to release nitric
      oxide and effect additional blood vessel relaxation.

      The goal of this proposal is to compare Nebivolol and Atenolol with respect to the following
      parameters:

        -  Plaque within arteries supplying the heart in terms of its volume and composition as
           assessed by ultrasound within these arteries.

        -  Ability of small arteries in the heart to open up and deliver an enhanced blood supply
           in response to drug called Adenosine (routinely used in the cardiac catheterization
           laboratory) as assessed by pressure and flow detecting catheters within these arteries.

        -  Ability of the inner lining of arteries that supply the heart to release a relaxing
           compound called nitric oxide in response to injection of Acetylcholine (also used in the
           cardiac catheterization laboratory) as assessed by squirting dye into these arteries

        -  Local forces that affect blood flow in the arteries supplying the heart as assessed by
           superimposing the above data into complex maps created offline at Georgia Institute of
           Technology.

      It is likely that Nebivolol causes the plaque within arteries supplying the heart to change
      from the 'vulnerable' type to the 'stable' type plaque. There are several features of
      "vulnerable plaques" that can be detected in arteries of the heart using intravascular
      ultrasound (a small ultrasound camera that goes in the arteries of the heart). The
      investigators hypothesis is that Nebivolol will prove superior to Atenolol in reducing
      'vulnerable plaques', improve blood flow within the small arteries and the health of inner
      lining of these arteries at the 1 year time point. The investigators plan to enroll 20
      patients into the study (26 patient including dropouts) who will be randomized in a 1:1
      manner to Nebivolol Vs Atenolol for 1 year and repeat evaluation at that time point.
    

Detailed description: 
      Primary hypothesis:

      Nebivolol therapy will reduce the number of thin-cap fibroatheromas, VH-IVUS defined
      "vulnerable plaques" compared to Atenolol in patients undergoing serial angiography and IVUS.

      Secondary Hypotheses:

        -  Nebivolol therapy will improve coronary microvascular function

        -  Nebivolol therapy will improve coronary endothelial function

        -  Nebivolol therapy will improve coronary wall shear stress

      Specific Aims:

      To evaluate, in patients with stable angina or acute coronary syndromes and moderate
      angiographic coronary artery disease, the effects of Nebivolol 5 mg a day compared to
      Atenolol 50 mg a day on:

        -  The number of thin cap fibroatheromas, percent necrotic core, and percent atheroma
           volume as defined by the novel Virtual Histology IVUS (VH™ IVUS).

        -  The coronary shear stress profile measured using 3 dimensional vessel reconstruction,
           flow velocity measurements, and computational fluid dynamics.

        -  Microvascular function as determined by coronary flow reserve and fractional flow
           reserve measured by invasive Doppler/pressure assessment.

        -  Endothelial function as determined by the response of quantitative coronary angiography
           and Doppler assessment to intracoronary acetylcholine challenge.
    

Intervention name(s): Nebivolol; Atenolol
Intervention type(s): Drug; Drug
Intervention description(s): 10 mg PO qday; 100 mg PO qday
Other intervention name(s): Bystolic; Senormin; Tenormin
Intervention MeSH terms: Atenolol; Nebivolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment