Initial combined treatment with anticholinergics and α-blockers for men with lower urinary tract symptoms related to BPH and overactive bladder: a prospective, randomized, multi-center, double-blind, placebo-controlled study

Abstract

Initial combined treatment with anticholinergics and a-blockers for men with lower urinary tract symptoms related to BPH and overactive bladder: a prospective, randomized, multi-center, double-blind, placebo-controlled study We aimed to evaluate the efficacy and safety of combination treatment using anticholinergics with a-blocker for initial treatment of both overactive bladder (OAB) and other lower urinary tract symptoms (LUTS), secondary to BPH. A 12-week, randomized, double-blind, placebo-controlled trial was conducted at four urology clinics in Korea, involving men, aged 50 years or older, with LUTS related to BPH and OAB. A total of 176 patients were randomly assigned to receive doxazosin (4 mg) plus placebo or doxazosin (4 mg) plus tolterodine SR (4 mg), once a day for 12 weeks. Changes from baseline in total International Prostate Symptom Score (IPSS), bladder diary variables, patient perception of bladder condition (PPBC), uroflowmetry, postvoid residual volume and IPSS subscores (voiding and storage) were analyzed. Of the 176 enrolled patients, 91 had doxazosin gastrointestinal therapeutic system (GITS) and placebo, and 85 had combined medication with doxazosin GITS and tolterodine SR. Compared with the doxazosin plus placebo group, the doxazosin plus tolterodine group showed significant reductions in IPSS storage subscore and improvement in the quality of life item, urgency episodes, as well as in micturition frequency at weeks 4 and 12. However, it failed to improve PPBC at week 4 as well as at week 12. Earlier intervention with anticholinergics plus a-blocker was tolerated well, including the questions about urinary retention (n ¼ 1) and dry mouth (n ¼ 2). Initial combination treatment of anticholinergics plus a-blocker showed positive results for men with LUTS related to BPH and OAB symptoms and did not increase the risk of urinary retention.

Acute Urinary Retention Rates in the General Male Population and in Adult Men With Lower Urinary Tract Symptoms Participating in Pharmacotherapy Trials: A Literature Review

“…No AUR cases were reported in a nonplacebo-controlled 12-week study in 176 men receiving doxazosin 4 mg/day. 12 In the PREDICT study (n ¼ 1095), in which men with LUTS/BPH were randomized to doxazosin, finasteride, combination therapy, or placebo for up to 1 year, there were no cases of AUR in any doxazosin-containing arm, compared with 4 (1.5%) in the placebo group. 13 In contrast, in the MTOPS study (n ¼ 3047), doxazosin 1-8 mg/day decreased the cumulative incidence of AUR over 4 years vs placebo: 9 (1.2%) vs 18 (2.4%) events, respectively, relative risk reduction (RRR) 50%, P ¼ .23.…”

“…39 The addition of tolterodine 2 mg or 4 mg to an a 1 -blocker yielded similar results, with 2 (0.3%; 16.0 per 1000 man-years) and 3 (0.5%; 21.8 per 1000 man-years) patients reporting AUR over 12 weeks. 46 Finally, a single case of AUR was reported in a 12-week study of combination therapy with tolterodine SR 4 mg þ doxazosin 4 mg. 12 Other Antimuscarinics. Few combination studies have been carried out with other antimuscarinics.…”

Clinical guidelines for male lower urinary tract symptoms associated with non-neurogenic overactive bladder

“…Urodynamic study for OAB in male LUTS LUTS in men is highly prevalent and storage LUTS is more prevalent than voiding or postmicturition symptoms. 7,11,51 Although OAB wet is usually associated with urodynamic DO, the OAB symptoms might involve other bladder dysfunction or outlet disorders. Initial treatment based on predominant symptoms without urodynamic testing is encouraging, but a urodynamic test is recommended when the initial management fails to resolve the storage LUTS.…”

Benign Prostat Hiperplazisi ve Antimuskarinik Tedavi

“…AAM ve BPH ile ilişkili AÜSS'si olan 50 yaş üzeri hastalarla yürütülen plasebo kontrollü, prospektif, randomize, çift kör bir çalışmada 12 haftalık (doksazosin+plasebo) ve (doksazosin+tolterodin) uygulaması sonrası yapılan değerlendirmede, kombine tedavi grubunda IPSS depolama semptom skorlarında, hasta bazlı QoL, urgency ve işeme sıklığında gelişme sağlanmış olup bir hastada AUR geliştiği belirtilmiştir. Aynı çalışmada Q max ve PVR' de gözle-nen değişiklikler konusunda, doksazosin+plasebo grubunda Q max 'ın ortalama 10,8 ml/sn' den 15,3 ml/ sn'ye, PVR'nin ortalama 34 cc' den 24 cc'ye gerilediği, doksazosin+tolterodin grubunda ise Q max 'ın 11,1 ml/ sn' den 14,2 ml/sn'ye, PVR'nin de ortalama 33 cc' den 36 cc'ye yükseldiği gözlenmiş, fakat istatistiksel olarak bu değişimlerin anlamlılık göstermediği ortaya konmuştur (21). Antimuskarinik tedavinin etkinliğinin ve güvenilirliğinin değerlendirildiği plasebo kontrollü, prospektif, randomize, çift kör bir başka çalışma-da (solifenasin+tamsulosin) ve (tamsulosin+plasebo) gruplarıyla 12 haftalık tedavi sonrasında kombine tedavi uygulanan grupta etkinlik açısından işeme sıklığı ve urgency atağında gerileme elde edilmiştir.…”