多沙唑嗪、非那雄胺及联合治疗对良性前列腺增生临床进展的长期影响。

The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.

作者信息

McConnell John D, Roehrborn Claus G, Bautista Oliver M, Andriole Gerald L, Dixon Christopher M, Kusek John W, Lepor Herbert, McVary Kevin T, Nyberg Leroy M, Clarke Harry S, Crawford E David, Diokno Ananias, Foley John P, Foster Harris E, Jacobs Stephen C, Kaplan Steven A, Kreder Karl J, Lieber Michael M, Lucia M Scott, Miller Gary J, Menon Mani, Milam Douglas F, Ramsdell Joe W, Schenkman Noah S, Slawin Kevin M, Smith Joseph A

机构信息

University of Texas Southwestern Medical Center, Dallas, TX 75390-9110, USA.

出版信息

N Engl J Med. 2003 Dec 18;349(25):2387-98. doi: 10.1056/NEJMoa030656.

DOI:10.1056/NEJMoa030656

PMID:14681504

Abstract

BACKGROUND

Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown.

METHODS

We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia.

RESULTS

The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone.

CONCLUSIONS

Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

摘要

背景

良性前列腺增生通常采用α-肾上腺素能受体拮抗剂（α受体阻滞剂）或5α-还原酶抑制剂进行治疗。这些药物单独或联合使用对临床进展风险的长期影响尚不清楚。

方法

我们进行了一项长期双盲试验（平均随访4.5年），纳入3047名男性，比较安慰剂、多沙唑嗪、非那雄胺及联合治疗对良性前列腺增生临床进展指标的影响。

结果

与安慰剂相比，多沙唑嗪（风险降低39%，P<0.001）和非那雄胺（风险降低34%，P=0.002）显著降低了总体临床进展风险，总体临床进展定义为美国泌尿外科学会症状评分、急性尿潴留、尿失禁、肾功能不全或复发性尿路感染较基线至少增加4分。联合治疗与安慰剂相比风险降低66%（P<0.001），显著大于单独使用多沙唑嗪（P<0.001）或非那雄胺（P<0.001）。联合治疗（P<0.001）和非那雄胺（P<0.001）显著降低了急性尿潴留风险及侵入性治疗需求，但多沙唑嗪未降低。多沙唑嗪（P<0.001）、非那雄胺（P=0.001）及联合治疗（P<0.001）均使症状评分显著改善，联合治疗优于单独使用多沙唑嗪（P=0.006）和非那雄胺（P<0.001）。