The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study

• Published in: European urology 2010-01, Vol.57 (1), p.123-131
• Main Authors: Roehrborn, Claus G, Siami, Paul, Barkin, Jack, Damião, Ronaldo, Major-Walker, Kim, Nandy, Indrani, Morrill, Betsy B, Gagnier, R. Paul, Montorsi, Francesco
• Format: Article
• Language: English
• Subjects: 5-alpha Reductase Inhibitors; Adrenergic alpha-Antagonists - adverse effects; Adrenergic alpha-Antagonists - therapeutic use; Aged; Azasteroids - adverse effects; Azasteroids - therapeutic use; Biological and medical sciences; Brazil; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Dutasteride; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - therapeutic use; Gynecology. Andrology. Obstetrics; Humans; Italy; Kaplan-Meier Estimate; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; North America; Proportional Hazards Models; Prostatic Hyperplasia - complications; Prostatic Hyperplasia - diagnosis; Prostatic Hyperplasia - drug therapy; Prostatic Hyperplasia - surgery; Risk Assessment; Risk Factors; Severity of Illness Index; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Time Factors; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary Retention - drug therapy; Urinary Retention - etiology; Urinary tract. Prostate gland; Urologic Surgical Procedures, Male; Urology
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2009.09.035

Abstract Background Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and prostatic enlargement. Objective To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention (AUR), BPH-related surgery, and BPH clinical progression over 4 yr in men at increased risk of progression. Design, setting, and participants The Combination of Avodart® and Tamsulosin (CombAT) study was a 4-yr, multicenter, randomised, double-blind, parallel-group study in 4844 men ≥50 yr of age with a clinical diagnosis of BPH, International Prostate Symptom Score ≥12, prostate volume ≥30 cm3 , prostate-specific antigen 1.5–10 ng/ml, and maximum urinary flow rate (Qmax ) >5 and ≤15 ml/s with minimum voided volume ≥125 ml. Intervention Oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. Measurements The 4-yr primary end point was time to first AUR or BPH-related surgery. Secondary end points included BPH clinical progression, symptoms, Qmax , prostate volume, safety, and tolerability. Results and limitations Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery. Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression. Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr. Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies, with the exception of an imbalance in the composite term of cardiac failure among the three study arms. The lack of placebo control is a study limitation. Conclusions The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement. Clinicaltrials.gov identifier NCT00090103 ( http://www.clinicaltrials.gov/ct2/show/NCT00090103 ).