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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 in those
with baseline SBP of 140 to 149 mm Hg and 150 to 159 mm Hg (the lowest 2 baseline
strata); in the highest 2 baseline strata (SBP 160–169 and 170–179 mm Hg), the reductions
in SBP with nebivolol 5 mg and nebivolol 20 mg in the 160 to 169-mm Hg baseline SBP
stratum and in DBP with nebivolol 20 mg in the 170 to 179-mm Hg baseline stratum were
significantly greater (P < 0.03) compared with placebo. The most common AE in the nebivolol 5−, 10−, and 20-mg
groups and the placebo group was headache (36/409 [8.8%], 25/410 [6.1%], 27/410 [6.6%],
and 10/156 [6.4], respectively), fol-lowed by fatigue (9/409 [2.2%], 10/410 [2.4%],
25/410 [6.1%], and 3/156 [1.9%]) and dizziness (6/409 [1.5%], 9/410 [2.2%], 15/410
[3.7%], and 4/156 [2.6%]).
Conclusion: The present analysis of pooled data from 2 previously published registration studies
found that nebivolol was associated with significant reductions in BP compared with
placebo in these patients with stage 1 or 2 hypertension, with a tolerability similar
to that of placebo.
Key words
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Article info
Publication history
Accepted:
August 23,
2009
Identification
Copyright
© 2009 Excerpta Medica Inc. All rights reserved. Published by Elsevier Inc.
