title: Nebivolol withdrawal results in blood pressure returning toward pretreatment levels, but without rebound symptoms: phase IV randomized trial.
abstract: Rapid withdrawal of antihypertensive drugs may lead to blood pressure (BP) increase above pretreatment values or symptoms such as palpitations, chest pain, and tremor. This phase IV trial assessed the consequences of abrupt and stepwise withdrawal of nebivolol, a β(1)-selective blocker, in individuals with stage I-II hypertension. After a 4- to 5-week placebo washout phase and 12-week single-blind nebivolol treatment (10-40 mg/day, titrated based on BP response), participants achieving BP control (systolic BP [SBP]/diastolic BP [DBP] <140/90 mm Hg) or response (SBP decrease ≥10 mm Hg or DBP decrease ≥5 mm Hg) entered a 4-week, randomized, double-blind phase of continued nebivolol treatment (n = 102) or withdrawal to placebo (n = 105). Primary and secondary efficacy measures were changes in mean sitting DBP and SBP, respectively, analyzed using an analysis of covariance model. Safety and tolerability were also assessed. In the withdrawal phase, nebivolol and placebo groups demonstrated mean DBP increases of 1.8 and 7.7 mm Hg, respectively (P < .001), and SBP increases of 3.5 and 7.6 mm Hg (P = .011). Twenty-three (22.5%) nebivolol-treated and 18 (17.1%) placebo-treated participants experienced a treatment-emergent adverse event. No adverse events associated with β-blocker withdrawal and considered causally related to nebivolol were reported. Nebivolol withdrawal resulted in a mean BP increase near pretreatment levels and was not associated with rebound hypertension.
authors.affiliation: National Research Institute, Los Angeles, CA 90057, USA. docl@clinical-studies.com
authors.forename: Andrew
authors.initials: A
authors.lastname: Lewin
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Lasseter
authors.forename: Fang
authors.initials: F
authors.lastname: Dong
authors.forename: John C
authors.initials: JC
authors.lastname: Whalen
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage; D001578:Benzopyrans / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D010975:Platelet Aggregation Inhibitors; D012189:Retrospective Studies; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D010975:Platelet Aggregation Inhibitors; D000068577:Nebivolol