EURURO Vol. 71 No. 4

578 692

progression, development of AUR, or need for surgical or
other interventions.
Several recently published systematic reviews have
sought to address the body of evidence on drug therapy for
LUTS attributed to BPH, but these either have not been
comprehensive or lacked a rigorous assessment of the
evidence quality beyond study design. Most notably, the
European Urology Association guidelines were based on a
systematic review that used the 2011 version of the Oxford
Center for Evidence-Based Medicine levels of evidence
. As a result, all evidence frommeta-analyses of RCTs or
individual trials were labeled as Level 1 evidence, which we
perceive to be misleading. A systematic review by Navara
et al used the same levels of evidence rating system
and focused on the newer AB silodosin, which it found as
effective as tamsulosin 0.4 mg yet with fewer AEs except
for abnormal ejaculation. Based on moderate SOE, our
analyses agreed with findings of similar comparative
effectiveness, but raised concerns about a less favorable
side-effect profile. With regards to phosphodiesterase
type-5 inhibitors (PDE-5 inhibitors), two systematic
reviews published in urology literature failed to rate the
quality of evidence and are therefore of limited value in
informing evidence-based clinical practice . The
most rigorous assessment of newer drugs for LUTS
attributed to BPH was conducted as part of the National
Institute for Health and Care Excellence guideline pub-
lished in 2010 with evidence updates added through
2014. While their evidence update references newer trial
evidence and other systematic reviews, they did not
conduct their own updated analysis, thereby resulting in
an evidence report lacking information on PDE-5 inhibi-
tors, anticholinergics, and mirabegron. Our study therefore
appears timely and makes an important contribution for
patients, providers, and health policy makers seeking to
assess the relative merits of newer agents for treating male
LUTS.
Some of the newer drugs included in this review such as
silodosin should be viewed as offering alternative treatment
options of possibly similar efficacy to existing agents rather
than superior management options, although often with
potentially greater harms. PDE-5 inhibitors may offer
conceptual advantages in patients suffering from both ED
and LUTS. Other new drugs appear either less effective or
the evidence for assessing their effectiveness was insuffi-
cient. It was notable that we only identified three eligible
trials of 5-ARIs. Given the well-defined track record of
established agents and their usually lower costs, existing
evidence supports older ABs and/or 5-ARIs as initial
pharmacologic options. Trials of antimuscarinics, which
are known to affect bladder contractility, often excluded
participants with higher postvoid residual urine volumes,
thereby excluding patients at highest risk for urinary
retention and affecting the applicability of their findings
to general medical practice in which an assessment of
postvoid residuals is not part of the routine care pathway.
Additional research would add valuable information on
the treatment of LUTS attributed to BPH. Most trials we
identified had a time horizon of 3 mo or less; trials with a
longer treatment duration that reflect real-life practice
would provide valuable information to assess durability of
effect, prevention of progression including risk of AUR and
need for surgical intervention, as well as long-term
compliance and harms. Although we found little benefit
of the newer drugs compared with or added to older ABs
overall, it is possible that they provide benefits to select
groups of patients. However, we identified few trials that
examined effects within our prespecified subgroups;
available analyses were posthoc, limiting the validity and
reliability of the evidence.
5. Conclusions
Our study found that none of the drugs or drug combina-
tions newly used to treat LUTS attributed to BPH was more
effective compared with older AB treatment. AEs of the new
drugs or drug combinations were similar or greater than
older ABs when AE evidence was sufficient to assess.
Evidence was generally insufficient to assess long-term
efficacy, prevention of symptom progression, or AEs. Given
the lack of superior effectiveness, less assurance of their
relative safety and likely greater cost, the value of newer
drugs alone or in combination for treating LUTS attributable
to BPH appears low.
Author contributions: Philipp Dahm had full access to all the data in
the study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Dahm, Brasure, Risk, Fink, Wilt.
Acquisition of data: Brasure, MacDonald, Olson, Nelson, Rwabasonga.
Analysis and interpretation of data: Dahm, Brasure, Risk, Fink, Wilt.
Drafting of the manuscript: Dahm, Brasure, MacDonald, Risk, Fink,
Wilt.
Critical revision of the manuscript for important intellectual content: Dahm,
Brasure, Risk, Fink, Wilt.
Statistical analysis: Dahm, MacDonald, Wilt.
Obtaining funding: Wilt.
Administrative, technical, or material support: Brasure, Nelson.
Supervision: Wilt.
Other: None.
Financial disclosures: Philipp Dahm certifies that all conflicts of interest,
including specific financial interests and relationships and affiliations
relevant to the subject matter or materials discussed in the manuscript
(eg, employment/affiliation, grants or funding, consultancies, honoraria,
stock ownership or options, expert testimony, royalties, or patents filed,
received, or pending), are the following: This project was funded under
Contract Number HHSA290201200016I from the Agency for Healthcare
Research and Quality, US Department of Health and Human Services. The
authors of this manuscript are responsible for its content. Statements in
the manuscript should not be construed as endorsement by the Agency
for Healthcare Research and Quality or the US Department of Health and
Human Services. The Agency for Healthcare Research and Quality retains
a license to display, reproduce, and distribute the data and the report
from which this manuscript was derived under the terms of the agency’s
contract with the author.
Funding/Support and role of the sponsor: This reported is based on
research conducted by the Minnesota Evidence-based Practice Center
under contract with the Agency for Healthcare Research and Quality,
Rockville, Maryland (Contract Number: HHSA290201200016I).
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