Comparison of the effects of bimatoprost 0.1% and timolol 0.5% on circadian intraocular pressure and blood pressure : interim analisis

Purpose:to investigate the 24-hour IOP lowering efficacy of Lumigan 0.01% administered once at night compared to Timolol 0.5% administered twice daily. Methods:in this 2x2 months, multicentre, prospective, cross-over, randomized, double masked active controlled clinical trial glaucoma or ocular hypertension subjects, after adequate washout, have been randomized to be treated with either Bimatoprost 0.1% administered once at night or Timolol 0.5% administered twice daily. After 8 weeks patients crossed over to the opposite treatment for further 8 weeks. IOP, heart rate (HR) and blood pressure (BP) have been measured at 8:00am, 12:00pm, 4:00pm, 8:00pm, 12:00am, 04:00am and 8:00am at baseline and after 8 weeks of each treatment. The primary outcome was the comparison of mean 24h IOP after 8 weeks of treatment with Lumigan 0.01% and Timolol 0.5%. Secondary endpoints included the comparison between groups of day and night IOP and of IOP at each time-point of the 24h curve. A mixed-model ANOVA was used to compare the IOP variables between groups including the following effects: patients as random effect, drug and interaction between drug and treatment sequence as fixed effects (to explore potential carry-over effects). Results:20 patients have been enrollled and after 8 weeks of treatment mean daily IOP was statistically significantly reduced compared to baseline with both treatments (-3.8 mmHg, 95%CI -3.12/-4.49 with Timolol 0.5%, p<0.001; -4.8 mmHg, 95%CI -4.01/-5.54 with Bimatoprost 0.1% , p<0.001) and was statistically significantly lower with Bimatoprost 0.1% (p=0.032). No interaction between drug and treatment sequence was detected indicating no carry-over effects between drugs. IOP was significantly lower compared to baseline at each individual time point of the 24h curve with Bimatoprost 0.1% while Timolol 0.5% showed no statistically significant effect on IOP during the night hours (12:00am and 04:00am). HR was significantly reduced during Timolol 0.5% treatment compared to baseline (69.04±9.15 vs 63.94±7.11 bpm, p<0.0001). Sistolic and diastolic BP were also significantly reduced during Timolol 0.5% treatment compared to baseline (systolic BP 132±14.3 vs 120.7±14.4 mmHg, p<0.0001; diastolic BP 79.7±6,8 vs 75.43±5.7 mmHg, p<0.0001). Conclusions:Bimatoprost 0.1% once at night is more effective than Timolol 0.5% twice daily in reducing the IOP at all time points of the 24h curve. Night time IOP under Timolol 0.5% seems not to be different than IOP after washout. Heart rate and blood pressure are significantly reduced by Timolol 0.5% treatment.