Abstract 14441: Betareceptor Blocker Therapy in Patients with Peripheral Arterial Disease: Results from the Double-Blind Randomized Nebivolol or Metoprolol in Arterial Occlusive Disease (NORMA) Trial
Objective: Their impact on vasomotor tone complicates the use of betareceptor blockers in patients with peripheral arterial disease (PAD). The betareceptor blocker Nebivolol possesses additional vasodilating, endothelium-dependent, NO-releasing which might be particularly beneficial in patients with PAD. This clinical trial was set out to evaluate the effects of Nebivolol on endothelial function, and claudication distance as well as its tolerability in patients with PAD. Metoprolol was used in comparison as a betareceptor blocker without vasodilating properties.
Methods: A total of 128 patients with intermittent claudication and essential hypertension were included and double-blind randomized to receive 5 mg Nebivolol (N=65) or 95 mg Metoprolol (N=63) once daily. Endpoints were changes in endothelial function assessed via determination of flow-mediated dilatation (FMD) of the brachial artery and changes in initial and absolute claudication distance (ICD/ACD) measured by constant-workload protocol, blood pressure and quality of life using the “Claudication Scale Questionnaire”. All endpoints were evaluated at inclusion and after a 48 week treatment period. The intention to treat population included 109 patients (84 %) with endpoint analysis.
Results: There was no significant change in FMD in patients treated with Nebivolol or Metoprolol (P=0.16). Walking distance improved significantly in both patient groups. ACD significantly increased in both treatment groups, while a significant increase of ICD could only be found in the Nebivolol group. Adjusted mean change of ACD was 21.7% in the Nebivolol group (P=0.03) and 23.5% in the Metoprolol group (P=0.02). Adjusted mean change of ICD was 33.9% after Nebivolol (P=0.003) and 16.6% after Metoprolol (P=0.12) treatment. Quality of life was not influenced by either treatment. Both drugs were equally effective in lowering the blood pressure.
Conclusions: Betareceptor blocker therapy was well tolerated in PAD patients with intermittent claudication during a treatment period of nearly one year. We found a significant prolongation of the absolute walking distance in both treatment groups while a significant improvement of the pain free walking distance could only be observed in the Nebivolol group.
- © 2010 by American Heart Association, Inc.