Clinical Trial: Study to Evaluate Effect of Nebivolol on Angina in Women With Microvascular Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Nebivolol for the Relief of Microvascular Angina in Women

Brief Summary: Women have less significant blockages of coronary arteries, however have greater symptoms and worse outcomes compared to their age-matched male counterparts. This paradox has led to the recognition and importance of the microvasculature ( small vessels) as a contributor to symptoms and outcomes. Nebivolol has unique antioxidant properties and dilates blood vessels and it is therefore proposed that treatment with nebivolol will reduce angina (chest symptoms) in women with microvascular disease as well as improve exercise capacity, reduce resource utilization and improve other measures of artery function.

Detailed Summary:

Though women have less obstructive coronary artery disease (CAD) they continue to have a greater burden of symptoms, more myocardial ischemia, and a higher rate of adverse outcomes than their age-matched male counterparts. This ostensible paradox has led to the recognition of a distinct pathophysiology of ischemic heart disease, in part related to microvascular dysfunction, and abnormal coronary reactivity. The term primary microvascular angina, (MVA) is used to describe a syndrome among patients who have symptoms suggestive of cardiac ischemia, evidence of electrocardiographic abnormalities, abnormalities on stress imaging or a history of ACS, but no evidence of obstructive epicardial coronary disease. In this population, microvascular angina causes significant morbidity and in some may contribute to increased mortality.

The treatment of microvascular disease remains empirical due to lack of data regarding symptom alleviation, as well as ultimate mortality reduction. Women with ischemic heart disease and microvascular angina continue to report more frequent angina and worse quality of life. They frequently seek medical attention for the evaluation of cardiovascular symptoms including chest pain and shortness of breath. Consequently, these women incur greater healthcare costs, with more office visits, hospitalizations, and myocardial infarctions. In fact, more than one half of women without obstructive coronary disease continue to have ischemic symptoms that lead to further consumption of CAD resources, most often because of diagnostic uncertainty.

In the absence of robust outcomes data to drive the care of these women with microvascular ischemia, various approaches are taken, in addition to the fundamental management of baseline risk factors. Some physicians treat these women as they would treat patients with known obstru
Sponsor: Massachusetts General Hospital

Current Primary Outcome: Seattle Angina Questionnaire Score [ Time Frame: 3 months ]

Original Primary Outcome: Seattle Angina Questionnaire Score [ Time Frame: 3 months ]

Current Secondary Outcome:

• Peak VO2 Measured by Cardiopulmonary Exercise Testing [ Time Frame: 3 months ]
  Assessment of exercise capacity (peak VO2) as determined by CPET
• Resource Utilization Questionnaire [ Time Frame: 3 months ]
  Resource utilization as determined by patient phone calls, office visits, emergency room visits, and number of hospitalizations, as well an index cost for any hospitalizations
• SF36 [ Time Frame: baseline and 12 week follow-up ]
  The SF-36v2 is a commonly used instrument to assess HRQoL8. The questionnaire evaluates 8 HRQoL domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The physical component score is a composite of the SF-36v2 physical health domains (physical functioning, role-physical, bodily pain and general health) and the mental component score a composite of the mental health domains (vitality, social functioning, role-emotional and mental health). Each HRQoL domain score ranges from 0 to 100, with higher scores corresponding to a better health status. The SF-36v2 domain scores were calculated using the QualityMetric Health Outcomes Scoring Software version 4.5.
• Exercise Duration [ Time Frame: 3 months ]
  Assessment of exercise duration as determined by CPET
• Peak Heart Rate as Measured by Cardiopulmonary Exercise Testing [ Time Frame: 3 months ]
  Assessment of peak heart rate as determined by CPET
• Peak O2 Pulse [ Time Frame: 3 months ]
  peak O2 pulse as measured by cardiopulmonary exercise testing

Original Secondary Outcome:

• Peak VO2 Measured by Cardiopulmonary Exercise Testing [ Time Frame: 3 months ]
  Assessment of exercise capacity (peak VO2) as determined by CPET, additional fitness parameters will include: VO2 at the anaerobic threshold, peak work-load, time-to-angina, aerobic efficiency and O2 pulse)
• Resource Utilization Questionnaire [ Time Frame: 3 months ]
  Resource utilization as determined by patient phone calls, office visits, emergency room visits, and number of hospitalizations, as well an index cost for any hospitalizations
• peripheral arterial tone and pulse wave analysis [ Time Frame: 3 months ]
  Peripheral arterial tone ( PAT) and pulse wave analysis to determine whether or not nebivolol leads to changes in vascular relaxation and stiffness among women with microvascular ischemia ( if additional funding can be obtained)
• circulating metabolites [ Time Frame: 3 months ]
  Blood samples will be collected into the edta tubes pre and post exercise at baseline and after 3 months of nebivolol treatment and stored at -80C. The list of metabolites assayed have been previously published by the investigators of this application. In brief, we have established a Lc-MS-based metabolomics platform that analysis approximately 300 human metabolites in a targeted manner. A metabolite can be identified by its parent mass and dominant daughter mass on a high resolution mass spectrometer in combination with its retention time on an appropriate LC column. The present platform can acquire the data for 300 metabolites in approximately 60 minutes from < 200ul of plasma.

Dates:
Date Received: August 9, 2012
Date Started: April 2013
Date Completion:
Last Updated: March 8, 2017
Last Verified: December 2016