Doxazosin for treating lower urinary tract symptoms compatible with benign prostatic obstruction: a systematic review of efficacy and adverse effects.
OBJECTIVE
To evaluate the efficacy and adverse effects of doxazosin for treating lower urinary tract symptoms (LUTS) compatible with benign prostatic obstruction (BPO).


METHODS
Randomized controlled trials were included in the meta-analysis if: the study duration was > or = 1 month; the study involved men with symptomatic BPO; and doxazosin was compared with placebo or active controls. Study and patient characteristics and outcome data were extracted in duplicate onto standardized forms using a prospectively developed protocol.


RESULTS
Thirteen studies involving 6033 men with (mean age 64 years) met the inclusion criteria; 10 were placebo-controlled, including two with combined doxazosin/finasteride therapy and finasteride monotherapy arms. Three trials were a comparison with other alpha-blockers. The study duration was 1-54 months. The mean baseline symptom scores and peak urinary flow (PUF) rates were indicative of moderate BPO. Doxazosin gave significant improvements in LUTS, assessed by symptom scores, vs placebo and finasteride in the short- to long-term. Two long-term studies (1 and 4 years) reported mean changes from baseline for the International Prostate Symptom Score of - 8.3 and - 6.6 points (-49% and - 39%) for doxazosin and - 5.7 and - 4.9 points (-33% and - 29%) for placebo, respectively. Doxazosin significantly increased PUF rates vs placebo. In pooled results from three studies, the weighted mean difference in the mean change from baseline vs placebo was 1.6 mL/s (95% confidence interval 1.2-2.1). Efficacy was comparable with other alpha1-blockers. In the long-term (>4 years) doxazosin was no better then finasteride in improving PUF. Combined doxazosin and finasteride significantly reduced the risk of overall clinical progression of BPO vs each drug separately in men followed for >4 years. Absolute risk reductions vs placebo were 11.3%, 6.9% and 6.4% for combined therapy, doxazosin and finasteride, respectively (P < 0.001). Improvements in symptom scores and PUF were also significantly greater with combined than monotherapy, and the former reduced the need for invasive treatment for BPO and the risk of long-term urinary retention, although the absolute reductions in risk vs placebo were small (<4%). Dizziness and fatigue were significantly more common with doxazosin than placebo (11% vs 7%, and 6% vs 3%, respectively). Adverse events reported for combined therapy were similar to those with each monotherapy.


CONCLUSIONS
The evidence indicates that doxazosin is effective and generally well tolerated for improving LUTS and PUF in men with symptomatic BPO. Combined therapy was better than doxazosin alone in reducing the risk of clinical progression of BPO and other long-term complications related to BPO.
MacDonald
Roderick
R
Minneapolis Veterans Affairs Center for Chronic Disease Outcomes Research, the Cochrane Review Group in Prostate Diseases and Urologic Cancers, Veterans Affairs Medical Center, Minneapolis 55417, USA.
Wilt
Timothy J
TJ
Howe
R William
RW
D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D018592:Cross-Over Studies; D017292:Doxazosin / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018120:Finasteride / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D016055:Urinary Retention / Q000188:drug therapy* / Q000209:etiology
D000317:Adrenergic alpha-Antagonists; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D018120:Finasteride; D017292:Doxazosin