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Evidence summaries

Combination of Doxazosin and Finasteride Compared with Either Drug Alone or Placebo for Benign Prostatic Hyperplasia

Long-term combination therapy with doxazosin and finasteride is effective in reducing the risk of overall clinical progression of benign prostatic hyperplasia significantly more than either drug alone. Level of evidence: "A"

The MTOPS trial 1, a double-blind multi-centre trial (mean follow-up, 4.5 years) involving 3047 men, compared the effects of placebo, doxazosin at a target dose of 8 mg/d, finasteride at a dose of 5 mg/d, and combination therapy. The baseline AUA symptom score was between 8 and 30, mean 17. The risk of overall clinical progression - defined as an increase above base line of at least 4 points in the AUA symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection - was reduced by doxazosin (39 percent risk reduction, 95% CI 20 to 53, ARR 6.9%, NNT = 15) and finasteride (34 percent risk reduction, 95% CI 14 to 50, ARR 6.4%, NNT = 16), as compared with placebo. Combination therapy reduced the risk by 66 percent (95% CI 54 to 76, ARR 11.2%, NNT = 9) as compared with placebo, which was significantly greater than the risk reduction associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. 16.6% of the placebo recipients reached the combined end point at 4 years. The need for invasive therapy was significantly reduced by combination therapy (RRR 67%, absolute risk reduction at 4 years 3.5%, NNT = 29) and finasteride (RRR 64%, ARR at 4 years 3.2%, NNT = 31) but not by doxazosin (RRR 3%). 5% of the placebo group needed invasive therapy. The use of either drug resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. The absolute increase of adverse events compared to placebo was between 2 and 3 per 100 patient years for erectile dysfunction in the finasteride groups and for dizziness and postural hypotension in the doxazosin groups.

A Cochrane review [Abstract] 2 on finasteride for benign prostatic hyperplasia included 23 studies with a total of 21 945 subjects. Only 2 studies compared finasteride and the alpha-blocker doxazosin; the above MTOPS trial and the PREDICT trial 3. At one year endpoint, PREDICT trial reported clinically significant mean changes of -6.6 and -8.3 points in the IPSS (range 0 to 35), for the finasteride (n=239) and doxazosin (n=250) arms, respectively. The inter group mean difference was 1.70 points (95% CI 0.58 to 2.82) and favored doxazosin. The absolute risks of acute urinary retention (RD 0.01, 95% CI -0.01 to 0.02) or of surgical intervention (RD 0.01, 95% CI -0.01 to 0.02) for finasteride versus doxazosin were not statistically significant. There was clinically significant score changes (HASH(0x2fcfe80) 4 point decrease in the AUASI/IPSS) of -8.5 and -6.6 points for combination therapy (finasteride+doxazosin, n=286) and finasteride (n=264), respectively. The inter group comparison was significant as well, and favored combination therapy (MD -1.90, 95% CI -3.11 to -0.69). The absolute risk of acute urinary retention was not significant (RD -0.01, 95% CI -0.03 to 0.00), and combination therapy decreased - insignificantly - the absolute risk of surgical intervention by 1% (RD -0.01, 95% CI -0.03 to 0.00). Mean changes from baseline for finasteride + doxazosin versus doxazosin monotherapy at one year were -8.5 and -8.3, for the IPSS. These were clinically meaningful changes, but were not significant head-to-head (MD -0.20, 95% CI -1.41 to 1.01).

    References

    • McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW, Lepor H, McVary KT, Nyberg LM Jr, 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, Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003 Dec 18;349(25):2387-98. [PubMed]
    • Tacklind J, Fink HA, Macdonald R, Rutks I, Wilt TJ. Finasteride for benign prostatic hyperplasia. Cochrane Database Syst Rev 2010;(10):CD006015. [PubMed]
    • Kirby RS, Roehrborn C, Boyle P, Bartsch G, Jardin A, Cary MM, Sweeney M, Grossman EB, Prospective European Doxazosin and Combination Therapy Study Investigators. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 2003 Jan;61(1):119-26. [PubMed]

Primary/Secondary Keywords