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

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(0x2f82cc8) 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

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