title: 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.
abstract: OBJECTIVE
  • 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.
  
  
  METHODS
  • The 4-year Combination of Avodart® 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. • Eligible patients received tamsulosin 0.4 mg, dutasteride 0.5 mg, or a combination of both. • 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
  • There were 4844 men in the intent-to-treat population. Overall baseline characteristics were similar across all patient groups. • 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. • 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). • 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. • 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
  • 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. • 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.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. claus.roehrborn@UTSouthwestern.edu
authors.forename: Claus G
authors.initials: CG
authors.lastname: Roehrborn
authors.forename: Jack
authors.initials: J
authors.lastname: Barkin
authors.forename: Paul
authors.initials: P
authors.lastname: Siami
authors.forename: Andrea
authors.initials: A
authors.lastname: Tubaro
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Wilson
authors.forename: Betsy B
authors.initials: BB
authors.lastname: Morrill
authors.forename: R Paul
authors.initials: RP
authors.lastname: Gagnier
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D000368:Aged; D001378:Azasteroids / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D000068538:Dutasteride; D004812:Epidemiologic Methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D013449:Sulfonamides / Q000627:therapeutic use*; D000077409:Tamsulosin; D016896:Treatment Outcome; D016055:Urinary Retention / Q000188:drug therapy* / Q000209:etiology / Q000601:surgery
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D013449:Sulfonamides; D000077409:Tamsulosin; D000068538:Dutasteride