The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia

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

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5α-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.

Original languageEnglish (US)
Pages (from-to)2387-2398
Number of pages12
JournalNew England Journal of Medicine
Volume349
Issue number25
DOIs
StatePublished - Dec 18 2003

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Doxazosin
Finasteride
Prostatic Hyperplasia
Urinary Retention
Risk Reduction Behavior
Therapeutics
Placebos
Receptors, Adrenergic, alpha
Placebo Effect
Adrenergic Antagonists
Urinary Incontinence
Urinary Tract Infections
Pharmaceutical Preparations
Renal Insufficiency
Oxidoreductases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia. / McConnell, John D.; Roehrborn, Claus; 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.

In: New England Journal of Medicine, Vol. 349, No. 25, 18.12.2003, p. 2387-2398.

Research output: Contribution to journalArticle

McConnell, JD, Roehrborn, C, Bautista, OM, Andriole, GL, Dixon, CM, Kusek, JW, Lepor, H, McVary, KT, Nyberg, LM, Clarke, HS, Crawford, ED, Diokno, A, Foley, JP, Foster, HE, Jacobs, SC, Kaplan, SA, Kreder, KJ, Lieber, MM, Lucia, MS, Miller, GJ, Menon, M, Milam, DF, Ramsdell, JW, Schenkman, NS, Slawin, KM & Smith, JA 2003, 'The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia', New England Journal of Medicine, vol. 349, no. 25, pp. 2387-2398. https://doi.org/10.1056/NEJMoa030656
McConnell, John D. ; Roehrborn, Claus ; 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. / The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia. In: New England Journal of Medicine. 2003 ; Vol. 349, No. 25. pp. 2387-2398.
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abstract = "BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5α-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.",
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T1 - The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia

AU - McConnell, John D.

AU - Roehrborn, Claus

AU - Bautista, Oliver M.

AU - Andriole, Gerald L.

AU - Dixon, Christopher M.

AU - Kusek, John W.

AU - Lepor, Herbert

AU - McVary, Kevin T.

AU - Nyberg, Leroy M.

AU - Clarke, Harry S.

AU - Crawford, E. David

AU - Diokno, Ananias

AU - Foley, John P.

AU - Foster, Harris E.

AU - Jacobs, Stephen C.

AU - Kaplan, Steven A.

AU - Kreder, Karl J.

AU - Lieber, Michael M.

AU - Lucia, M. Scott

AU - Miller, Gary J.

AU - Menon, Mani

AU - Milam, Douglas F.

AU - Ramsdell, Joe W.

AU - Schenkman, Noah S.

AU - Slawin, Kevin M.

AU - Smith, Joseph A.

PY - 2003/12/18

Y1 - 2003/12/18

N2 - BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5α-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.

AB - BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5α-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.

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