title: Efficacy and safety of tadalafil 5 mg once daily in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia in men aged ≥75 years: integrated analyses of pooled data from multinational, randomized, placebo-controlled clinical studies.
abstract: To assess efficacy and safety of tadalafil in men aged ≥75 years with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) and additional safety in men aged ≥75 years with erectile dysfunction (ED).
  
  
  
  We conducted an integrated analysis of 12 phase II-III randomized, double-blind and/or open-label extension studies to evaluate short-term (12-26 weeks) efficacy and short- and longer-term (42-52 weeks) safety in men aged <75 years vs men aged ≥75 years. All men received once-daily tadalafil 5 mg or placebo. The efficacy outcome was International Prostate Symptom Score (IPSS). Safety measurements included treatment-emergent adverse events (TEAEs), adverse events (AEs) leading to discontinuation, serious AEs (SAEs), and cardiovascular AEs. All analyses were intention-to-treat. Changes from baseline to efficacy endpoint and differences in changes between treatment groups were estimated as least-squares means using analysis of covariance models.
  
  
  
  Change in the mean IPSS was significantly different in men aged <75 years vs those aged ≥75 years across tadalafil and placebo groups (treatment-by-age interaction P = 0.034). Tadalafil was not statistically significantly better than placebo in men aged ≥75 years, but effect size varied between studies. Maintenance of efficacy with tadalafil was observed across age groups. Short-term tadalafil safety findings for men aged <75 vs ≥75 years included: TEAEs (52 [33.8%] vs 503 [30.1%]), AEs leading to discontinuation (3 [1.9%] vs 50 [3.0%]), SAEs (4 [2.6%] vs 15 [0.9%]) and cardiovascular AEs (4 [2.6%] vs 30 [1.8%]). Long-term tadalafil safety data did not reveal clinically relevant differences between age groups. Limitations include exclusion of men with serious co-existing conditions and limited sample sizes of men aged ≥75 years.
  
  
  
  Efficacy with once-daily tadalafil 5 mg in the treatment of LUTS/BPH differed between men aged <75 vs ≥75 years, with significant efficacy in the <75-year age group. The older age group had more concomitant diseases and used more drugs, which may have reduced efficacy. The small sample size precluded uni-/multivariate analyses to assess plausible interference from confounding factors. Tadalafil had a reassuring safety profile and no evidence of increased cardiovascular AEs in aging men.
authors.affiliation: Department of Urology, Hannover Medical School, Hannover, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Oelke
authors.affiliation: Geriatric Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Wagg
authors.affiliation: Medicines Development Unit Japan, Eli Lilly Japan, Kobe, Hyogo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takita
authors.affiliation: Eli Lilly Biomedicines BU - Men's Health Therapeutic Area Europe, c/o Lilly Deutschland, GmbH, Bad Homburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Büttner
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Viktrup
mesh_terms: D000368:Aged; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011470:Prostatic Hyperplasia / Q000150:complications*; D016032:Randomized Controlled Trials as Topic; D000068581:Tadalafil / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil
keywords: #UroBPH; #erectiledysfunction; benign prostatic hyperplasia; elderly; lower urinary tract symptoms; tadalafil