Clinical outcomes after combined therapy with dutasteride plus tamsulosin or either monotherapy in men with benign prostatic hyperplasia (BPH) by baseline characteristics: 4-year results from the randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) trial.

Treatment of benign prostatic hyperplasia (BPH) centres on two drug classes, 5 alpha-reductase inhibitors and alpha-blockers. The 4-year Combination of Avodart (R) and Tamsulosin (CombAT) study investigated whether the combination of dutasteride and tamsulosin was more effective than either monotherapy in reducing the relative risk of AUR, BPH-related surgery, and BPH clinical progression in men with moderate-to-severe LUTS who were at increased risk of disease progression. Data from the 2- and 4-year, pre-planned primary and secondary endpoint analyses for the CombAT study have been reported previously. This study reports the outcomes of post hoc analyses of the influence of baseline parameters on the incidence of AUR, BPH-related surgery, and overall clinical progression in patients treated with tamsulosin, dutasteride, or combination therapy with both agents. OBJECTIVE center dot To investigate the influence of baseline variables on the 4-year incidence of acute urinary retention (AUR), benign prostatic hyperplasia (BPH)-related surgery and overall clinical progression in men treated with tamsulosin, dutasteride, or a combination of both. PATIENTS AND METHODS center dot The 4-year Combination of Avodart (R) and Tamsulosin (CombAT) study was a multicenter, randomized, double-blind, parallel-group study of clinical outcomes in men aged >= 50 years with symptomatic (International Prostate Symptom Score [IPSS] >= 12) BPH, with prostate-specific antigen (PSA) levels of >= 1.5 ng/mL and < 10 ng/mL, and a prostate volume (PV) of >= 30 mL. center dot Eligible patients received tamsulosin 0.4 mg, dutasteride 0.5 mg, or a combination of both. center dot The primary endpoint was time to first AUR or BPH-related surgery. Secondary endpoints included clinical progression of BPH and symptoms. Posthoc analyses of the influence of baseline variables (including age, IPSS health-related quality of life [HRQL], PV, PSA, IPSS, peak urinary flow rate [Q(max)] and body-mass index [BMI]) on the incidence of AUR or BPH-related surgery, clinical progression of BPH, and symptoms were performed. RESULTS center dot There were 4844 men in the intent-to-treat population. Overall baseline characteristics were similar across all patient groups. center dot Regardless of baseline subgroup, the incidence of AUR or BPH-related surgery was higher in men treated with tamsulosin than in those treated with dutasteride or combined therapy. center dot Combined therapy was statistically better than tamsulosin in reducing the risk of AUR or BPH-related surgery in subgroups of baseline PV > 42.0 mL, in all subgroups of baseline PSA level, and all other baseline subgroups (P < 0.001). center dot Across treatment groups, the incidence of clinical progression was highest in men with a baseline IPSS of < 20 or IPSS HRQL score of < 4. The incidence of clinical progression was also higher in men receiving tamsulosin than dutasteride or combined therapy in all baseline subgroups, except for men with a baseline PV of < 40 mL. Combined therapy reduced the relative risk (RR) of clinical progression compared with tamsulosin across all baseline subgroups and compared with dutasteride across most baseline subgroups. center dot Symptom deterioration was the most common progression event in each treatment group regardless of baseline subgroup, except in those men with an IPSS of >= 20 at baseline. Combined therapy reduced the RR of symptom deterioration compared with tamsulosin across all but one baseline subgroup (the reduction was not significant for men with a baseline PV of < 40 mL) and compared with dutasteride in most subgroups. CONCLUSIONS center dot Men with a baseline PV of >= 40 mL and any baseline PSA level of >= 1.5 ng/mL had greater reductions in the RR of AUR or BPH-related surgery and greater reductions in the RR of clinical progression and symptom deterioration on combined therapy or dutasteride monotherapy than on tamsulosin monotherapy. center dot These analyses support the long-term use of combined therapy with dutasteride plus tamsulosin in men with moderate-to-severe BPH symptoms and a slightly enlarged prostate.