Efficacy and tolerability of nebivolol monotherapy by baseline systolic blood pressure: A retrospective analysis of pooled data from two multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging studies in patients with mild to moderate essential hypertension

• Published in: Clinical therapeutics 2009-09, Vol.31 (9), p.1946-1956
• Main Author: Germino, F. Wilford, MD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Antihypertensive Agents - therapeutic use; Antihypertensives; Arterial hypertension. Arterial hypotension; baseline blood pressure; Benzopyrans - administration & dosage; Benzopyrans - adverse effects; Benzopyrans - therapeutic use; Beta blockers; Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Blood Pressure - drug effects; Cardiology. Vascular system; diastolic blood pressure; Dose-Response Relationship, Drug; Double-Blind Method; Ethanolamines - administration & dosage; Ethanolamines - adverse effects; Ethanolamines - therapeutic use; Female; Humans; Hypertension; Hypertension - drug therapy; Internal Medicine; Male; Medical Education; Medical sciences; Middle Aged; Nebivolol; Overweight; Pharmacists; Pharmacology. Drug treatments; Primary care; Randomized Controlled Trials as Topic; Retrospective Studies; severity; Severity of Illness Index; stage 2 hypertension; Trends; Young Adult; β-blockers
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2009.08.028

Abstract Background: In clinical studies, nebivolol at doses of 2.5 to 40 mg once daily was associated with significant decreases in systolic blood pressure (SBP) and diastolic BP (DBP) in patients with hypertension and was well tolerated. Objectives: This post hoc analysis of pooled data from 2 previously published registration studies was conducted to further evaluate the antihypertensive efficacy and tolerability of nebivolol in patients with mild to moderate (stage 1–2) hypertension. Methods: The 2 trials were similarly designed multicenter, 12-week, randomized, double-blind, placebocontrolled, parallel-group, dose-ranging studies in patients 18 years of age and older with stage 1 or 2 hypertension (SBP 140–159 mm Hg and/or DBP 90–99 mm Hg [stage 1] or SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg [stage 2]). The primary efficacy end point of the 2 studies was the change from baseline in mean trough SiDBP at week 12. A secondary end point was the change from baseline to week 12 in mean trough sitting SBP (SiSBP). The present analysis included only patients who received nebivolol 5, 10, or 20 mg (the doses were common to both studies) or placebo, including analyses stratified by baseline SBP, although DBP represented a criterion for entry into the studies. Baseline SBP stratification levels were 140 to 149 mm Hg, 150 to 159 mm Hg, 160 to 169 mm Hg, and 170 to 179 mm Hg. For the tolerability analysis, the prevalences of treatment-emergent adverse events (AEs) were compared between the 3 nebivolol dose groups and the placebo group. Results: Of the 1716 randomized patients who received study medication in the 2 trials, data from 1385 patients were included in this pooled analysis (759 men, 626 women; median age, ~54 years; 13.6% black). Mean (SD) baseline SiSBP and SiDBP values were 151.9 to 152.7 and 99.2 to 99.5 mm Hg, respectively. Reductions from baseline in trough SiSBP were −10.8 (13.5), −10.7 (14.7), and −12.4 (15.5) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with −4.5 (13.4) mm Hg with placebo (all, P < 0.001). Reductions from baseline in trough SiDBP (the primary end point) were −9.8 (7.9), −10.5 (8.2), and −11.1 (8.6) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with −5.1 (8.1) mm Hg with placebo (all, P < 0.001). In a subgroup of 1227 patients stratified by baseline SBP, the reductions in SBP and DBP were significantly greater ( P < 0.03 and P < 0.001, respectively) with nebivolol at each dose compared with placebo i