Effect of nebivolol on nitric oxide availability and ADMA concentration in CAD patients after PCI: Prospective randomized double-blind study

Background: Endothelial dysfunction, defined by decreased bioavailability of nitric oxide (NO) and increased levels of asymmetric dimethylarginine (ADMA), has been proposed to play a central role in Coronary Artery Disease (CAD) pathophysiology. A selective β-blocker, nebivolol, could offer benefits in affecting this pathway after revascularization. Objective: The objective of this study is to determine the influence of nebivolol on serum NO levels and ADMA in patients with CAD who underwent successful elective percutaneous coronary intervention (PCI). Methods: In this prospective randomized double-blind placebo-controlled clinical study, 172 subjects with confirmed obstructive CAD and scheduled for PCI were recruited. After successful revascularization, patients were randomized to receive nebivolol 5 mg once daily ( n = 89) or placebo ( n = 83) for 42 days. Serum NO (μmol/L) and ADMA (ng/mL) were assessed at baseline and day 42 by colorimetry and ELISA, respectively. Paired t-tests and Analysis of Covariance (ANCOVA) analyses were performed for comparisons within and between the groups, respectively, after adjustment for baseline values. Results: The baseline clinical parameters and biomarker values were found to be equivalent between groups. After 42 days of therapy, there was a marked increase in serum NO levels among the nebivolol group (from 85.25 ± 9.8 to 128.47 ± 6.2; p < 0.001), whereas there was no change in the placebo group ( p = 0.85). Simultaneously, there was a decrease in the levels of ADMA in the nebivolol-treated subjects (from 169.68 ±12.8 to 153.70 ±12.7; p < 0.001) and no change in the placebo-treated group. The ANCOVA analysis between the two groups for both markers was found to be highly significant at Day 42 ( p < 0.001), independent of concomitant medications or baseline profiles. Conclusion: In patients after PCI, treatment for 42 days was found to significantly enhance NO availability and decrease systemic ADMA concentration by nebivolol. These results clearly establish that nebivolol has the potential to restore vascular homeostasis in the high-risk vascular window, hence making it an ideal supplementary treatment for patients having atherosclerotic diseases.