Effects of systemic beta-blocker therapy on the efficacy and safety of topical brimonidine and timolol. Brimonidine Study Groups 1 and 2.
OBJECTIVE
To determine the impact of coadminstration of systemic beta-blockers on the ocular hypotensive efficacy and safety of topical timolol, a nonselective, beta-blocker, and that of brimonidine, an alpha2-selective adrenergic agonist, in patients with glaucoma or ocular hypertension.


METHODS
Post hoc evaluation of data collected from two prospective, multicenter, randomized, double-masked, parallel-group, actively-controlled, 12-month clinical trials.


METHODS
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 beta-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 beta-blockers, and mean intraocular pressure (IOP) reduction, adverse events, heart rate, and blood pressure were compared.


METHODS
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 beta-blockers had smaller decreases in IOP, a greater mean change in systolic (at week 2, months 1, 2, 6, and 9; P < or = 0.001) and diastolic blood pressure (months 2 and 6; P < or = 0.02), and a significantly greater mean decrease in heart rate (month 6; P = 0.004) compared with timolol subjects not taking systemic beta-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 beta-blocker therapy compared with brimonidine subjects not receiving systemic beta-blockers.


CONCLUSIONS
Concurrent systemic beta-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 beta-blockers, such as the alpha2 agonist brimonidine, may be a more appropriate first-line therapy for ocular hypertension and glaucoma patients concurrently taking systemic beta-blockers.
Schuman
J S
JS
New England Eye Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. jss@mediaone.net
D000284:Administration, Oral; D000287:Administration, Topical; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D004311:Double-Blind Method; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy; D009883:Ophthalmic Solutions / Q000627:therapeutic use; D011446:Prospective Studies; D011810:Quinoxalines / Q000627:therapeutic use*; D012449:Safety; D013999:Timolol / Q000627:therapeutic use*
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D013999:Timolol