Long-term efficacy of nebivolol monotherapy in patients with hypertension

Background: The antihypertensive activity of beta-blockers generally increa ses during the first 6 to 8 weeks of treatment; however, no study has syste matically assessed whether blood pressure continues to decrease with prolon ged treatment. Nebivolol is a third-generation beta-blocker that combines b eta-blocking activity with nitric oxide-mediated vasodilatory properties. I t is not known whether this combination of properties provides better long term control of blood pressure than other monotherapies. Objectives: The purpose of this study was to determine whether the antihype rtensive activity of nebivolol continues to increase over a 6-month period and to assess the efficacy and safety of nebivolol monotherapy over 6 month s in previously untreated and treated hypertensive patients. Methods: Patients who had not been treated previously for hypertension took nebivolol 5 mg once daily. Those who had been treated previously replaced their monotherapy with nebivolol 5 mg once daily starting the day after the first evaluation. Patients were evaluated at baseline and 1/2, 2 1/2, and 6 months after nebivolol treatment and were defined as responders if their diastolic blood pressure (DBP) was < 90 mm Hg or the decrease in DBP versus baseline was > 10 mm Hg. Patients answered a self-administered questionnai re about general feelings of well-being, compliance with treatment, and sid e effects. Results: A total of 3741 patients were enrolled; 1656 patients had been tre ated previously for hypertension. A total of 461 (12.3%) patients did not c omplete the study. In previously untreated patients, nebivolol reduced bloo d pressure by 19/11 mm Hg after 1/2 month and by 24/14 mm Hg after 6 months . In previously treated patients, mean blood pressure reductions were 9/7 m m Hg after 1/2 month and 14/8 mm Hg after 6 months (P < 0.001 for all diffe rences from baseline). After 2 1/2 months of treatment, blood pressures wer e not significantly different from those obtained at 1/2 month; however, bl ood pressures at 6 months were significantly different from those measured at 1/2 month (P < 0.05). After 1/2 month, 61% of previously untreated patie nts and 52% of treated patients were responders; after 6 months 86% and 74% , respectively, were responders (P < 0.01, 1/2 vs 6 months for both treated and untreated patients). Serious adverse effects considered unrelated to t he study drug were dementia, malignancy, myocardial infarction, and septic shock. Minor adverse effects were mild and included transient headache (1.9 %), dizziness (1.3%), and fatigue (1.3%) and were not considered reasons fo r withdrawal; 97 patients (2.6%) preferred not to continue the trial becaus e of side effects. After 6 months, 73% of patients (95% CI, 60%-82%) report ed that their general feeling of well-being had improved during the past 6 months, whereas only 5% reported that it had deteriorated. Among previously treated patients, 67%, (95% CI, 54%-76%) reported at 6 months that they to lerated nebivolol better than their previous treatment, whereas only 2.4%, reported that the previous treatment was better tolerated (P < 0.001 for bo th comparisons). Conclusion: In this study nebivolol was effective and well tolerated in the long term, and its antihypertensive activity continued to increase during the first 6 months of treatment.