Effects of Topical Bimatoprost 0.01% and Timolol 0.5% on Circadian IOP, Blood Pressure and Perfusion Pressure in Patients with Glaucoma or Ocular Hypertension: A Randomized, Double Masked, Placebo-Controlled Clinical Trial

Abstract

Purpose: To compare the 24-hour (24h) effects on intraocular pressure (IOP) and cardiovascular parameters of timolol 0.5% and bimatoprost 0.01% in open angle glaucoma and ocular hypertensive subjects.

Methods: In this prospective, randomized, double masked, crossover, clinical trial, after washout from previous medications enrolled subjects underwent 24h IOP, blood pressure (BP) and heart rate (HR) measurements and were randomized to either topical bimatoprost 0.01% at night plus placebo in the morning or to timolol 0.5% bid. After 8 weeks of treatment a second 24h assessment of IOP, BP and HR was performed and then subjects switched to the opposite treatment for additional 8 weeks when a third 24h assessment was performed. The primary endpoint was the comparison of the mean 24h IOP after each treatment. Secondary endpoints included the comparisons of IOP at each timepoint of the 24h curve and the comparison of BP, HR, ocular perfusion pressure and tolerability.

Results: Mean untreated 24h IOP was 20.3 mmHg (95%CI 19.0 to 21.6). Mean 24h IOP was significantly lower after 8 weeks of treatment with bimatoprost 0.01% than after 8 weeks of treatment with timolol 0.5% bid (15.7 vs 16.8 mmHg, p = 0.0003). Mean IOP during the day hours was significantly reduced from baseline by both drugs while mean IOP during the night hours was reduced by -2.3 mmHg (p = 0.0002) by bimatoprost 0.01% plus placebo and by -1.1 mmHg by timolol 0.5% bid (p = 0.06). Timolol 0.5% significantly reduced the mean 24h systolic BP from baseline, the diastolic BP during the day hours, the HR during the night hours, and the mean 24h systolic ocular perfusion pressure.

Conclusion: Both Bimatoprost 0.01% and Timolol 0.5% are effective in reducing the mean 24h IOP from an untreated baseline but Bimatoprost 0.01% is more effective than timolol 0.5% throughout the 24h. Timolol 0.5% effect on IOP is reduced during the night hours and is associated with reduced BP, HR and ocular perfusion pressure.

Trial registration: EU Clinical Trial Register and EudraCT# 2010-024272-26.

Fig 1. Study flow diagram.

Fig 2. Intraocular pressure at each time point of the daily curve.

Error bars represents standard error; * = p<5% for timepoint comparison versus baseline; § = p<5% for timepoint comparison between timolol 0.5% bid and bimatoprost 0.01% plus placebo.

Fig 3. Systolic (A) and diastolic (B) blood pressure and heart rate (C) at each timepoint of the 24h curve at baseline (continuous line), during timolol 0.5% bid (dashed line) and during bimatoprost 0.01% plus placebo treatment (dotted line).

Bpm = beats per minute. Error bars represents standard error; * = p<5% for timepoint comparison versus baseline; § = p<5% for timepoint comparison between timolol 0.5% bid and bimatoprost 0.01% plus placebo.

Fig 4. Display of the mean 24 hour IOP (A), systolic BP (B), diastolic BP (C) and heart rate (D) of the two arms of the study at baseline, at 8 weeks before the crossover and at 16 weeks after the crossover.

The dotted line indicates the study arm that received bimatoprost 0.01% plus placebo as first treatment and timolol 0.5% bid as second treatment. The continous line indicates the study arm that received timolol 0.5% bid as first treatment and bimatoprost 0.01% plus placebo as second treatment. IOP = intraocular pressure, BP = blood pressure.