Editing Functional: Pharmacological Management of LUTS (section)

== Combinations ==

=== Alpha-blockers and 5-ARIs ===
* '''<span style="color:#ff00ff">MTOPS</span>'''§
** '''Population: 3047 men age ≥ 50 with IPSS 8-30, PSA ≤ 10 ng/mL, Qmax ≥4 but ≤15 ml/s with minimum voided volume ≥125 ml'''
*** '''Mean prostate volume: 36mL'''
*** '''Mean PSA: 2.4ng/mL'''
** '''Randomized to placebo, doxazosin, finasteride, or combination therapy'''
** '''Primary outcome: overall clinical progression, defined as the first occurrence of:'''
**# '''≥ 4 points increase from baseline AUA symptom score'''
**# '''Acute urinary retention'''
**# '''Renal insufficiency'''
**# '''Recurrent UTI'''
**# '''Urinary incontinence'''
** Secondary outcomes: changes over time in the AUA symptom score and the maximal urinary flow rate
** '''Results:'''
*** '''Mean follow-up: 4.5 years'''
*** '''Rate of overall clinical progression:'''
**** Placebo 4.5 per 100 person-years
**** '''Doxazosin''': 2.7 per 100 person-years '''(P<0.001)'''
**** '''Finasteride''': 2.9 per 100 person-years '''(P=0.002)'''
**** '''No difference between doxazosin alone vs. finasteride alone'''
**** '''Combination therapy: 1.5 per 100 person-years (P<0.001), a significantly greater reduction than doxazosin alone (P<0.001) or finasteride alone (P<0.001)'''
* '''<span style="color:#ff00ff">CombAT</span>'''§
** '''Population: 4844 men age ≥ 50''' with a clinical diagnosis of BPH, '''IPSS ≥ 12,''' '''prostate volume ≥ 30g''', PSA 1.5-10 ng/ml, Qmax >5 but ≤15 ml/s with minimum voided volume ≥125 ml
*** '''Mean prostate volume: 55mL (larger than MTOPS)'''
*** '''Mean PSA: 4.0ng/mL (higher than MTOPS)'''
** '''Randomized to daily tamsulosin, dutasteride, or a combination of both (no placebo)'''
** '''Primary end point: time to first AUR or BPH-related surgery'''
** Secondary end points included BPH clinical progression, symptoms, Q(max), prostate volume, safety, and tolerability
*** BPH clinical progression defined as one of the following: symptom deterioration by International Prostate Symptom Score ≥4 points on two consecutive visits; BPH-related AUR; BPH-related urinary incontinence; recurrent BPH-related urinary tract infection or urosepsis; BPH-related renal insufficiency
** '''Results''':
*** '''Combination therapy was significantly better than tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery'''
*** '''Combination therapy was significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression'''
*** '''Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr.'''
* '''Summary of evidence for combination alpha-blockers and 5-ARIs from these trials:'''
** '''Combination better reduces risk of clinical progression and symptoms benefit at 4 years'''
** '''Monotherapy with 5-ARI and alpha-blockers are equally effective in risk of overall clinical progression'''
** '''5-ARI reduces risk of AUR or BPH-related surgery, addition of tamsulosin does not increase benefit'''

=== Alpha-blockers and anti-cholinergics ===
* Several RCTs have demonstrated that the '''combination treatment of anti-cholinergics and α1-blockers was more effective at reducing male LUTS''' '''than α1-blockers alone in men with OAB and coexisting bladder outlet obstruction'''
* '''α1-blockers and anti-cholinergics may have an additional synergistic effect on the bladder in the neurogenic population'''. This suggests that targeting multiple receptors may maximize the effectiveness of pharmacologic treatment of neurogenic bladder and should be considered in patients in whom treatment with antimuscarinics alone fails

=== Beta-3-agonist and anti-cholinergics ===
* '''Mirabegron combination therapy with solifenacin''' '''demonstrated greater efficacy than solifenacin''' alone on voided volume and micturition frequency.
** The enhanced efficacy with the combination was of a magnitude that is probably similar to the enhanced '''efficacy one might expect from uptitrating the dose of the anti-cholinergic'''. However, the '''combination was not associated with the adverse effects one would expect to encounter with higher doses of antimuscarinics.'''

=== Combining anti-cholinergics ===
* '''Needs further investigation''' to verify its efficacy as a non-invasive alternative for patients in whom anti-cholinergic monotherapy fails.

=== Anti-cholinergics and 5-ARIs ===
* '''Anti-cholinergics are safe and effective in selected patients with OAB and BPO when used in combination with 5-ARIs'''