Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24-hour heart rate response in patients on treatment for glaucoma

PURPOSE: Topical beta-blocker treatment is routine therapy in the managemen t of patients with glaucoma. Therapy results in systemic absorption, howeve r, the degree of reduction of resting and peak heart rate has not been quan tified. DESIGN: This trial evaluated the effect of placebo, 0.5% aqueous timolol (t imolol solution) and a 0.5% timolol suspension that forms a gel on applicat ion to the conjunctiva (timolol gellan) on the 24-hour heart rate in patien ts currently being treated for glaucoma to quantify the reduction in mean h eart rate. METHODS: Forty-three Caucasian patients with primary open-angle glaucoma or ocular hypertension with a mean (+/- SD) age of 63 (+/-8) years were rando mized and crossed over in a double-masked manner to 14 days of treatment wi th placebo (morning and evening in both eyes), timolol solution (morning an d evening in both eyes), or timolol gellan (morning in both eyes with place bo in the evening). On the 13th day of each period, heart rate was recorded continuously during a typical, ambulant 24-hour period. RESULTS: Both timo lol solution and timolol gellan reduced the mean 24-hour heart rate compare d with placebo (P less than or equal to .001), and this reduction was most pronounced during the daytime (-7.5% change in mean heart rate, -5.7 beats/ min). Timolol gellan showed a numerically but not significantly smaller red uction in 24-hour heart rate, compared with timolol solution. During the ni ght, the mean 12-hour heart rate on placebo and timolol gellan were both si gnificantly less than on timolol solution; the difference between solution and gellan treatments was statistically significant (P = .01). CONCLUSIONS: Both timolol solution and timolol gellan decrease the mean 24- hour heart rate compared with placebo. This response was most pronounced du ring the active daytime period. These data quantify the modest bradycardia associated with ophthalmic beta -blocker therapy in a typical patient popul ation on therapy for glaucoma. Although exercise performance was not assess ed in this trial, reductions of this magnitude should not have substantial clinical consequences. (C) 2001 by Elsevier Science Inc. All rights reserve d.