Effects of Nebivolol on Aortic Compliance in Patients With Diabetes and Maximal Renin Angiotensin System Blockade: The EFFORT Study

Abstract

The beneficial effects of nebivolol on arterial stiffness and endothelial dysfunction are well documented in untreated hypertensive patients and differ from nonvasodilatory bblockers. This study tests the hypothesis that the addition of nebivolol in predominantly African American patients with type 2 diabetes already receiving maximally tolerated doses of renin-angiotensin system (RAS) blockers will further improve large artery compliance. Patients with type 2 diabetes and hypertension on maximal RAS blockade (n=70) were randomized to nebivolol or metoprolol succinate daily. Doses were titrated until systolic blood pressure (SBP) was <130 mm Hg. Radial artery applanation tonometry and pulse wave velocity (PWV) analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits at intervals during a 6-month period. Nebivolol decreases oxidative stress in primary hypertension and increases NO bioavailability through upregulation of endothelial NO synthase (eNOS) and reduction of circulating asymmetric dimethylarginine (ADMA). 5,6 Nebivolol administration also restores NO bioavailability in endothelial cells obtained from African Americans who have an impaired release of NO to conventional stimuli.

Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol

“…Finally, in AA patients with stage 1 hypertension, nebivolol monotherapy increased flow‐mediated dilation and improved arterial wave reflections compared with untreated patients . In contrast, no differences between metoprolol succinate and nebivolol were observed in aortic compliance indices in a largely AA population of diabetics …”

“…50 In contrast, no differences between metoprolol succinate and nebivolol were observed in aortic compliance indices in a largely AA population of diabetics. 51 Moreover, these experiments were performed in the setting of prostacyclin inhibition. The contribution of the prostacyclin pathway was thus not investigated in this study and may also potentially be affected by b-blockade.…”

Перспективи Широкого Застосування Небівололу В Лікуванні Хворих На Артеріальну Гіпертензію В Поєднанні З Різною Коморбідною Патологією

“…Терапия небивололом больных АГ и СД 2-го типа приводила к достоверному снижению САД и ДАД, уменьшению гликемии, показателей общего холестерина и холестерина липопротеидов низкой плотности [20]. У больных АГ с СД добавление к базисной терапии метопролола сукцината приводило к достоверному увеличению уровня гликозилированного гемоглобина, а при использовании небиволола данный показатель не изменялся [21].…”

A Review of Nebivolol Pharmacology and Clinical Evidence

“…Compared with metoprolol, nebivolol reduces plasma ADMA levels and the augmentation index (AIx) [ 20 ], a surrogate measure of arterial stiffness that is also associated with cardiovascular risk [ 21 ]. However, the AIx benefits compared with metoprolol may not extend to individuals with hypertension and diabetes mellitus who are receiving maximal tolerated doses of renin-angiotensin-aldosterone system (RAAS) blockers [ 22 ]. Of note, a 12-month randomized trial that compared the effects of nebivolol and metoprolol on a number of hemodynamic and biochemical parameters found no difference in AIx and ADMA levels between the two groups, but demonstrated that only nebivolol had a beneficial effect on oxidative stress [ 23 ] and significantly reduced central systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and left ventricular wall thickness [ 24 ].…”