Patients with BPH being treated with combination therapy for LUTS are more likely to be able to stop the alpha blocker treatment than the 5-alpha reductase inhibitor (5-ARI), a study from Taiwan suggests.

Men with LUTS secondary to BPH were assessed for suitability for combination therapy, and those with IPSS ≥ 8 (at least moderate symptoms), total prostate volume (TPV) > 30 ml (at least moderately enlarged) and flow rate < 5 ml/sec (significantly reduced suggesting outflow obstruction) were randomised to two arms.

Patients in both arms took a combination of dutasteride (0.5 mg qds) and doxazosin (4 mg qds) for two years. One arm then discontinued the 5-ARI while the other discontinued the alpha blocker.

Primary outcome was the number of patients resuming the discontinued medication. The secondary outcomes were changes in parameters such as IPSS, TPV and flow rates, plus the need for prostate surgery e.g. TURP.

A total of 117 and 113 patients, mean age 75, completed the study in the discontinue 5-ARI (DC5-ARI) and the discontinue alpha blocker (DCAB) arms respectively. Discontinuation of either medication led to an increase in symptoms as measured by the IPSS. The increases were 6 points for DC5-ARI and 5 points for DCAB, with no statistical significance in this difference. However, evidence suggests that a change in IPSS ≥ 3 points is detectable to patients, so changes of this order are likely to be noticeable to men.

Resumption of combination therapy was significantly more common in the DC5-ARI group than the DCAB, 51.3% compared with 31.0%, P = 0.005. Mean time before resumption of combination therapy was 5.0 ± 4.4 months in the DCAB group compared with 7.8 ± 3.8 months in the DC5-ARI group, P < 0.05, reflecting the difference in mechanism of action of these two drug classes.

TPV progression was significantly higher in the DC5-ARI than the DCAB group, 29.1% compared with 8.0%, P < 0.001. Significantly more men in the DC5-ARI group required TURP – 14.5% compared with 7.1% in the DCAB group (P = 0.043). This is consistent with the findings of other studies which clearly demonstrate that it is the 5-ARI component of combination therapy that protects men from acute retention and the need for surgery, whereas alpha blocker therapy has little impact on this risk.

For higher risk men, combination therapy is the gold standard. Many patients - and their GPs - will want to minimise the amount of medication they take, particularly as many of these older men may face problems with polypharmacy.

There are a number of messages for primary care. First, it is not unreasonable for men to trial discontinuing one component of combination therapy, but they need to be aware that there is a good chance that they will see some deterioration in symptom control as a result. They will then need to decide if this change is acceptable.

The exception to this appears to be men with significantly reduced flow rates, who as a subgroup appear to do worst from discontinuation of combination therapy and may be best advised to continue if treatment is well tolerated.

Second, this study discontinued one component after two years of combination therapy – previous studies have suggested that it takes almost 18 months for combination therapy to be maximally effective, and it is probably sensible therefore to treat patients with a combination for at least 9-12 months before considering discontinuation of one component.

Third, for most men, it is the alpha blocker component of combination therapy that should be discontinued, because of the protective effect conferred by 5-ARIs against the risk of retention, the need for surgery, and the evidence from this study that this is less likely to result in resumption of combination treatment later on.

Dr Jonathan Rees

• Lin V C-H, Liao C-H, Kuo H-C. Progression of lower urinary tract symptoms after discontinuation of 1 medication from 2-year combined alpha-blocker and 5-alpha reductase inhibitor therapy for benign prostatic hyperplasia in men - A randomized multicenter study. Urology 2014;83: 416-421