Evaluation of The Effects of Nebivolol in Comparison to Atenolol on Wall Shear Stress and Rupture Prone Coronary Plaques

The Evaluation of The Effects of Nebivolol in Comparison to Atenolol on Wall Shear Stress and Rupture Prone Coronary Artery Plaques in Patients With Moderate Coronary Artery Disease

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.

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.

Inclusion Criteria:

• Patients with stable angina or acute coronary syndrome
• Moderate coronary lesion (defined as a lesion significant enough by the treating physician to warrant further evaluation using CFR or FFR or intravascular ultrasound assessment).
• Lesion located in the proximal 60mm of the RCA or LAD.
• On stable medical therapy for other cardiac risk factors.

Exclusion Criteria:

• Left Main lesion greater than 50% stenosis
• Patients with a history of coronary artery bypass surgery
• Severe valvular heart disease
• Patients presenting with a STEMI.
• Inability to provide informed consent prior to randomization
• Creatinine >1.5
• Lesions located beyond 60mm in an epicardial vessel
• Coronary anatomy requiring CABG
• B-blocker, calcium channel blocker or extended-release nitrate therapy within last 48 hours.
• Bradycardia (HR<50 bpm)
• Hypotension (SBP<100mmHg)
• Severe COPD by pulmonary function testing