Effect of Nebivolol on Endothelial Dysfunction in Coronary Artery Disease Patients -An Open Label Randomized Controlled Clinical Trial (NEDCAD)

Abstract

Background: Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity in India. Oxidative stress and endothelial dysfunction play a major role in the pathophysiology of the disease. Nebivolol a third generation beta blocker is claimed to have additional vasodilatory and antioxidant properties. Studies comparing Nebivolol with older beta blockers such as metoprolol in hypertensive patients have demonstrated improvement in endothelial dysfunction. There are only limited studies showing the effect of Nebivolol on endothelial dysfunction in patients with coronary artery disease. Hence this study aimed to compare the effect of Nebivolol and metoprolol on oxidative stress and endothelial function in patients with coronary artery disease and hypertension. Methods: A total of 62 patients participated in the study, out of which 32 patients received Nebivolol 5 mg/day and 30 patients received metoprolol 50 mg/day. 5 ml of blood was taken at baseline and after 4 weeks of therapy to estimate concentration of malondialdehyde, total antioxidant status and intercellular adhesion molecule-1. Brachial artery ultrasonography was done to assess the flow mediated dilation before and after study drug therapy. Results: The reduction in MDA was detected after 4 weeks of therapy with both Nebivolol (1.4 ± 0.54 vs 1.2 ± 0.55, p=0.03) and metoprolol (1.6 ± 0.32 vs 1 ± 0.60, P = 0.0003). Brachial artery ultrasonography done in 15 patients did not show any significant increase in the lumen diameter or FMD after one month of therapy in both arms of the study. Fatigue was reported less commonly in patients receiving Nebivolol (3 vs 12, p=0.007). Conclusion: Nebivolol (5 mg/day) has antioxidant benefit in patients with coronary artery disease and hypertension. The drug is well tolerated. The improvement in endothelial function could not be demonstrated in our study. Larger studies need to be carried

Nebivolol in the treatment of arterial hypertension

“…These results are hence in line with the previously mentioned studies displaying the beneficial effects of nebivolol on endothelial dysfunction. [41][42][43][44][45][46] These effects have been related to nebivolol's well-established anti-oxidative properties, which were depicted again in the NEDCAD trial, 87 but were surprisingly more evident in the metoprolol group.…”

Nebivolol in the treatment of systemic hypertension

“…[20] Bu olumlu etkiler nebivolol'ün vasküler yatakta yarattığı anti oksidatif özelliklerine dayanır. [21] Bilindiği gibi endotel işlev bozukluğu esansiyel hipertansiyon gelişimi ve KV komplikasyonlar için risk faktörü olarak kabul edilir. Diğer beta blokerlerin aksine nebivolol'ün antihipertansif etkisi aynı zamanda endotel işlev bozukluğundaki düzelmeye bağlıdır.…”