This retrospective analysis in a UK GP primary care database complements previous UK studies of LUTS/OAB and LUTS/BPO [19–21]. The study highlights the relatively low use of combination treatments that target OAB. Only a small proportion of LUTS (including OAB) patients were prescribed mirabegron with an antimuscarinic agent. However, use of this combination may have increased since the publication of studies such as BESIDE in 2016, SYNERGY in 2017 and SYNERGY II in 2018, which showed benefits of combination versus an antimuscarinic alone [8, 22, 23]. It was also notable that around 5% each of men and women receiving OAB drugs were on a combination of two or more antimuscarinic agents (Tables 2a and 3), despite a lack of evidence supporting any benefit of this approach.
Our study also highlights the relatively low treatment rates for storage symptoms in men. In the EPIC study, of all men identified with LUTS, over 80% had storage LUTS . In the EpiLUTS study , storage symptoms were experienced by around two-thirds of men. Storage symptoms can be highly bothersome in men, even more so than voiding symptoms . However, in our study only around a quarter of all men being treated for LUTS received treatment specifically targeting storage symptoms (i.e., an antimuscarinic and/or mirabegron alone or combined with a BPO drug), although this figure refers only to men with treated LUTS, in contrast to the other studies which were based on the general population. Thus, some men with storage symptoms may be receiving inadequate treatment in clinical practice, despite storage symptoms often being the most bothersome component of LUTS .
Alpha-blockers are the usual first-line treatment for men with LUTS suggestive of BPO [5, 26], including the approximately 50% of men with mixed storage and voiding symptoms . The European Association of Urology guidelines  recommend a combination of an alpha-blocker with an OAB drug in moderate-to-severe LUTS if treatment with monopharmacotherapy has been insufficient to relieve storage symptoms. As the available evidence suggests one-third of these men with mixed symptoms will respond adequately to alpha-blocker monotherapy , we might expect to see OAB/BPO drug combination therapy in up to one-third of all men being treated for LUTS. However, in the current study, only 7% were receiving alpha-blocker plus antimuscarinic combination treatment therapy (and only 8% were on any OAB/BPO drug combination), which is consistent with another UK study in which 15% of men with mixed LUTS were reported to be receiving an alpha-blocker combined with an antimuscarinic agent .
The reasons for the low treatment of storage symptoms in men may be historical, reflecting overemphasis on the prostate-related component of LUTS rather than bladder-related issues. Furthermore, there may be a perceived risk of precipitating urinary retention when using bladder antimuscarinic agents in men with evidence of obstruction, although the available evidence suggests that this risk is low . There is already good evidence supporting the use of alpha-blocker/antimuscarinic combination pharmacotherapy in men with mixed symptoms [15, 16]. More recently, two randomized, placebo-controlled trials have also demonstrated that mirabegron add-on therapy in men who have residual OAB symptoms while being treated with tamsulosin for LUTS is both effective and well-tolerated [17, 28]. It is hoped that this new evidence will help to improve the overall management of men with mixed symptoms.
Antimuscarinic agents and beta-3 agonists are recommended first-line pharmacological treatments for both men and women with OAB [6, 7] and men with moderate-to-severe LUTS with predominant bladder storage symptoms . However, with antimuscarinics, long-term persistence is often poor due to unmet treatment expectations or adverse events . In our study, mirabegron monopharmacotherapy had the highest persistence (both in men and women). Several observational studies also reported higher persistence with mirabegron vs antimuscarinics [21, 30]. Persistence was greater with monopharmacotherapy than in combination pharmacotherapy, and was particularly poor with combinations of two antimuscarinics in both men and women.
For monopharmacotherapy targeting BPO and voiding symptoms (e.g. alpha-blockers and 5-ARIs), persistence was highest for doxazosin and finasteride, but this was not evident in sensitivity analyses based on confirmed LUTS diagnosis. This suggests that the higher persistence with these agents in the main sub-cohorts may be driven by their use in other disorders (e.g., doxazosin for hypertension) and it is notable that only 3% of patients on doxazosin had a LUTS diagnostic code.
A limitation of our study is that in CPRD GOLD, GPs do not systematically report prescriptions issued in secondary care, and reasons for discontinuation were not available in CPRD, which limits interpretation of persistence results. In addition, some treatments are prescribed for conditions other than OAB, LUTS, BPO or SUI (e.g., doxazosin, finasteride and duloxetine), which may influence some of the treatment pattern and/or persistence estimates. The inclusion of fixed-dose combinations may increase the overall persistence with tamsulosin/solifenacin combination pharmacotherapy ; for tamsulosin/dutasteride fixed-dose combination, the available evidence suggests it may have no impact on persistence . Finally, as this study was performed using a UK general practice database, it is unclear to what extent the results would be generalizable to other healthcare systems.