OBJECTIVES: To compare the effectiveness and costs of â-blockers, combined with alpha-2 agonists or carbonic anhydrase inhibitors (CAI), as replacements for failed first-line treatments in glaucoma, according to the United Kingdom General Practitioner Research Database (UK-GPRD). METHODS: Data on treated ocular hypertension or glaucoma patients (topical, surgical or laser treatments) were extracted. Target patients were prescribed â-blockers with alpha-2 agonists or CA inhibitors as replacements for failed treatment regimens. A subsequent change of prescription (addition or removal of a topical treatment) constituted a treatment failure. Times to treatment failure, during a specified observation period, were compared using an adjusted Cox model. Drug consumption, clinic visits and glaucoma procedures during the period were subjected to a cost minimization analysis, adopting the NHS perspective. RESULTS: Out of 56,612 patients elicited, 39,808 received at least one topical prescription for glaucoma. Amongst these, 1,164 were prescribed a â blocker+alpha-2 agonist and 5,581 a â blocker+CAI, in place of failed treatments for glaucoma. No significant demographic differences were observed between groups. The mean age was 68.1 years and 51.9% were female. By the end of one year 69.7% of patients failed to respond to â blocker+alpha-2 as did 59.5% to â blocker+CAI (p<0.001). The hazard ratio (0.818) for failure was less for â blocker+CAI (p<0.001) than â blocker+alpha-2, after adjusting on age, gender, and comorbidities. Adjusted costs of â blocker+alpha-2 regimens were estimated at £357 p.a. and were not statistically different (p=0.61) from â blocker+CAI regimens (£348 p.a.). CONCLUSION: According to UK-GPRD information, â blocker+CAI is more efficient than â blocker+alpha-2 in replacing failed treatments for glaucoma. Patients continued longer with â blocker+CAI treatment than â blocker+alpha-2, at a similar cost.