Effects of systemic β-blocker therapy on the efficacy and safety of topical brimonidine and timolol

Abstract

Purpose To determine the impact of coadminstration of systemic β-blockers on the ocular hypotensive efficacy and safety of topical timolol, a nonselective β-blocker, and that of brimonidine, an α 2-selective adrenergic agonist, in patients with glaucoma or ocular hypertension. Design Post hoc evaluation of data collected from two prospective, multicenter, randomized, double-masked, parallel-group, actively-controlled, 12-month clinical trials. Participants Of the 926 subjects with ocular hypertension or glaucoma that were enrolled in the two prospective trials, 66 (7.1%) were concurrently maintained on systemic β-blocker therapy. Of these patients, 34 had been assigned to the brimonidine group and 32 to the timolol group. Methods Subjects instilled into each eye either 1 drop of brimonidine 0.2% or timolol 0.5% twice daily for 1 year. Study subjects within medication treatment groups were classified as to their use or nonuse of concurrent systemic β-blockers, and mean intraocular pressure (IOP) reduction, adverse events, heart rate, and blood pressure were compared. Main outcome measures Mean IOP reduction from baseline was the primary efficacy variable. Adverse events and mean changes in heart rate and blood pressure from baseline were the primary safety variables. Results Timolol-treated subjects concurrently taking systemic β-blockers had smaller decreases in IOP, a greater mean change in systolic (at week 2, months 1, 2, 6, and 9; P ≤ 0.001) and diastolic blood pressure (months 2 and 6; P ≤ 0.02), and a significantly greater mean decrease in heart rate (month 6; P = 0.004) compared with timolol subjects not taking systemic β-blockers. By contrast, there was a modest enhancement of IOP-lowering efficacy at trough and no effect on blood pressure or heart rate in brimonidine-treated subjects who were concurrently receiving systemic β-blocker therapy compared with brimonidine subjects not receiving systemic β-blockers. Conclusions Concurrent systemic β-blocker therapy had no deleterious effect on ocular hypotensive efficacy and no impact on systemic safety parameters with topical brimonidine, whereas efficacy was reduced and systemic safety parameters were impacted with topical timolol. Ocular hypotensive agents other than β-blockers, such as the α 2 agonist brimonidine, may be a more appropriate first-line therapy for ocular hypertension and glaucoma patients concurrently taking systemic β-blockers.