Clinical Question: Is the combination of finasteride and doxazosin more effective than either drug alone in the treatment of patients with benign prostatic hyperplasia (BPH)?
Setting: Outpatient (any)
Study Design: Randomized controlled trial (double-blinded)
Synopsis: Doxazosin is an alpha blocker that reduces smooth muscle tone in the prostate and bladder neck; finasteride is a 5-alpha-reductase inhibitor that reduces prostate volume. Although it makes sense that there may be greater benefit in combining the drugs than in using each alone, short-term studies have not demonstated greater benefit.
In this study, men with BPH were randomized (allocation concealed) to doxazosin (4 to 8 mg per day, as tolerated), finasteride (5 mg orally per day), a combination of the drugs, or neither. A total of 3,047 men were recruited at 17 centers. All participants had an American Urological Association (AUA) score of at least 8, in which zero = no symptoms and 35 = severe symptoms. Groups were balanced at the start of the study, and analysis was by intention to treat. Men with hypotension, a prostate-specific antigen (PSA) level greater than 10 ng per mL, or previous prostate surgery were excluded.
The primary outcomes were worsening in the AUA score of at least four points, acute urinary retention, renal insufficiency, recurrent urinary tract infection, and urinary incontinence. At the end of the four-year study, the primary outcomes were significantly less likely to occur in the combination-therapy group (5 percent) than in the groups getting either drug alone (10 percent each) or no drug at all (17 percent). Twenty patients would have to be treated with combination therapy instead of doxazosin or finasteride alone for four years to prevent BPH from progressing in one patient. Most adverse events were more common in the combination-therapy group, although this difference was only significant for abnormal ejaculation, peripheral edema, and dyspnea. The benefit of combination therapy was greatest in patients with a prostate volume of more than 40 mL and a PSA level higher than 4 ng per mL.
Bottom Line: Combination therapy with finasteride and doxazosin for at least four years reduces the risk of clinical progression of BPH. However, long-term use of finasteride also is associated with an increased risk of high-grade prostate cancer (Thompson IM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med July 17, 2003;349:215–24). Until this risk is better elucidated, combination therapy should be limited to patients who have a prostate volume greater than 40 mL, a PSA level greater than 4 ng per mL, and a clear understanding of the risks and benefits of therapy. (Common POEM) (Level of Evidence: 1b)