Cardiovascular Drugs and Therapy 17 257–263 2003 C  2003 Kluwer Academic Publishers. Manufactured in The Netherlands CLINICAL PHARMACOLOGY AND DRUG STUDIES Comparison of the New Cardioselective Beta-Blocker Nebivolol with Bisoprolol in Hypertension: The Nebivolol, Bisoprolol Multicenter Study (NEBIS) Istvan Czuriga 1 , Igor Riecansky 2 , Juraj Bodnar 3 , Tibor Fulop 1 , Valeria Kruzsicz 1 , Eva Kristof 1 , and Istvan Edes 1 , for the NEBIS Investigators Group 1 Department of Cardiology, University of Debrecen, Hungary; 2 Slovak Cardiovascular Institute, Bratislava; 3 Clinic of Internal Medicine, Kosice, Slovakia Summary. Objective: The aim of the present study was to evaluate the antihypertensive efficacy of the highly beta 1 - selective adrenergic antagonist nebivolol in comparison with bisoprolol in the treatment of mild to moderate es- sential hypertension. Methods: This multicenter, single-blind, randomized, parallel-group 16-week study involved a 4-week placebo run-in, followed by a 12-week treatment period (5 mg nebivolol or 5 mg bisoprolol). Patients (n = 273) eligible for the study had a sitting diastolic blood pressure (DBP) between 95 and 110 mm Hg and a systolic blood pressure (SBP) ≤180 mm Hg at the end of the placebo run-in period. The primary endpoint of the study was the percentage of responders achieving DBP normalization (≤90 mm Hg) or a DBP reduction of at least 10 mm Hg. Results: The baseline SBP and DBP were similar in the two groups. Both SBP and DBP decreased gradually and significantly upon treatment. The two treatments had sim- ilar effects on the mean change from the baseline for both DBP (nebivolol -15.7 ± 6.4 mm Hg vs. bisoprolol -16.0 ± 6.8 mm Hg) and SBP. A high proportion of responders was noted in both groups (nebivolol 92.0% vs. bisoprolol 89.6%) and there was no significant difference between the treat- ments. The overall number and incidence of spontaneously reported adverse events were slightly, but not significantly lower for nebivolol (8 events; 5.8%) than for bisoprolol (12 events; 8.9%). Conclusions: The findings of the present trial indicate that 5 mg nebivolol once daily is an effective antihyperten- sive agent. It can therefore be recommended as a useful alternative first-line treatment option for the management of patients with mild to moderate essential hypertension. Key Words. nebivolol, bisoprolol, beta-adrenergic receptor antagonist, hypertension Introduction Beta-adrenergic receptor antagonists are widely used in cardiovascular therapy. Since the early 1960s, when they were introduced for the treatment of angina pectoris and arrhythmias, there has been continu- ing progress in the field of beta-blockade. Numerous studies have confirmed the beneficial effects of beta- blockers in various forms of ischemic heart disease, heart failure, hypertension and a wide variety of other conditions, such as pheochromocytoma, portal hypertension, hyperkinetic heart syndrome and hy- perthyroidism [1]. The pharmacological development has had the aim of improving the beta 1 -selectivity of the agents, and additional vasodilator activities (alpha-adrenergic receptor blockade or other mecha- nisms including endothelium derived nitric oxide) were recently introduced. Basically, the beta-adrenergic blocking agents differ in various aspects. Non-selective drugs block both beta 1 - and beta 2 -receptors, while the beta 1 -selective drugs block primarily the cardiac and other beta 1 -adrenoceptors [1]. Beta-adrenergic block- ing agents with other vasodilatory properties have also been introduced, such as the alpha-adrenergic recep- tor blocker carvedilol [2] or the NO synthesis pathway stimulator nebivolol [3,4]. The mode of action of beta-blockers in hyperten- sion is not fully understood. Initially, it was sug- gested that the decreased cardiac output is responsi- ble for the blood pressure-lowering effect [1] of the beta-adrenergic blocking agents. However, additional mechanisms, e.g. the inhibition of renin release, may contribute to the pressure-lowering effects, especially in the later phase of treatment. The effects of cate- cholamines on inotropy and renin release are mainly mediated by the beta 1 -receptors; consequently it has been suggested that the beta 1 -receptor selective an- tagonists may control hypertension more effectively than non-selective agents [5–7]. Moreover, it has been This study was sponsored by Berlin-Chemie AG, Menarini Group, Berlin, Germany. Address for correspondence: Istvan Edes, Department of Car- diology, University of Debrecen, P.O.B. 1, H-4004 Debrecen, Hungary. Tel./Fax: 36-52-414928; E-mail: edes@jaguar.dote.hu 257