Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?
The purpose of this study is to evaluate if a drug called nebivolol can reverse inappropriate left ventricular mass (LVM) when compared to the standard of care drug metoprolol.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
|Official Title:||Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?|
- Inappropriate LVM [ Time Frame: 18 months ] [ Designated as safety issue: No ]Presence of inappropriate LVM (if a previously clinically indicated echocardiography exam or other imaging method providing patient's LVM is available): LVM is inappropriate when observed LVM (oLVM) exceeds predicted LVM (pLVM) by more than 28%, that is, 100×(oLVM/pLVM) >128% .
- Echo measures of LV function [ Time Frame: 18 months ] [ Designated as safety issue: No ]we will test whether ad-vanced echo measures of LV function are altered in the patients with LVM, and whether their values significantly change after treatment with nebivolol or metoprolol.
|Study Start Date:||June 2012|
|Study Completion Date:||March 2013|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
|Active Comparator: Nebivolol||
Nebivolol 2.5 mg once daily
Other Name: Bystolic
Comparator from the same drug class, but without known vasodilating effects
Drug: Metoprolol succinate
Metoprolol succinate 50 mg once daily
Other Name: Toprol XL
In response to chronic pressure overload by arterial hypertension, the cardiac left ventricle undergoes hypertrophy, that is, increases its wall thickness and, therefore, its mass, to sustain the elevated workload. Such anatomical remodeling can be considered adaptive or appropriate. However, in a considerable number of patients with arterial hypertension, the increase in the left ventricular mass is excessive and, thus, inappropriate.
Ventricular mass is inappropriate when its amount surpasses the physical need of the ventricle to sustain the elevated workload. Therefore, ventricular mass can be inappropriate even in patients without arterial hypertension or without hypertrophy identified by echocardiography (echo). We can mathematically predict an appropriate amount of mass and observe the actual mass in individual patients based on ventricular workload and wall thickness, respectively, noninvasively evaluated by echo. By comparing the observed ventricular mass to the predicted one, we determine whether its amount is inappropriate. It follows that by therapeutically normalizing blood pressure in hypertension and thus eliminating the elevated workload, then any ventricular hypertrophy represents an inappropriate mass.
Inappropriate ventricular mass is proven to have a detrimental effect on long-term cardiovascular event-free survival, and ventricular hypertrophy is increasingly recognized as a potent risk factor of cardiovascular morbidity and mortality, and all-cause mortality. Ventricular performance is altered in hypertension with inappropriate mass, but this alteration can be subtle enough to escape detection using current echocardiography measures. Hence, patients with hypertension, who have inappropriate left ventricular mass, need to be specifically identified by analysis of the predicted and observed ventricular mass, and the therapeutic goal must include management of elevated blood pressure as well as reversal of the excessive ventricular mass.
In this double-blind prospective study, patients with hypertension and inappropriate ventricular mass will be randomized to therapy with nebivolol or metoprolol to find out whether nebivolol could reverse inappropriate left ventricular mass, thus providing a benefit beyond what is achieved by mere blood pressure reduction alone. If confirmed, this will represent a significant ancillary ability of nebivolol and be a key step towards therapy of inappropriate ventricular mass, which is a so far unmanaged cardiovascular risk and a poor event-free prognostic factor.
|United States, Arizona|
|Mayo Clinic Arizona|
|Scottsdale, Arizona, United States, 85259|
|Principal Investigator:||Marek Belohlavek, MD, PhD||Mayo Clinic|