title: Adherence to initial PDE-5 inhibitor treatment: randomized open-label study comparing tadalafil once a day, tadalafil on demand, and sildenafil on demand in patients with erectile dysfunction.
abstract: BACKGROUND
  Phosphodiesterase type 5 (PDE-5) inhibitor treatment for erectile dysfunction (ED) is frequently discontinued; adherence may vary depending on the initial regimen.
  
  
  OBJECTIVE
  To evaluate the effects of initiating treatment with tadalafil once a day (OaD), tadalafil on demand (pro re nata [PRN]), or sildenafil PRN on treatment adherence.
  
  
  METHODS
  In this multicenter, open-label study, men (≥ 18 years) with ED, naïve to PDE-5 inhibitors, were randomized (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8-week randomized treatment (RT) period (dose adjustment possible) was succeeded by 16 weeks of pragmatic treatment (switches between PDE-5 inhibitors allowed).
  
  
  METHODS
  Treatment adherence was measured as time to discontinuation of RT (any cause), estimated by Kaplan-Meier product-limit method. Treatment-group differences were estimated as hazard ratio (HR; Cox proportional hazards).
  
  
  RESULTS
  Seven hundred seventy patients (mean age 53 years) were randomized to tadalafil OaD (N = 257), tadalafil PRN (N = 252), and sildenafil PRN (N = 261). Kaplan-Meier estimates for patients discontinuing RT were 52.2, 42.0, and 66.7%, respectively. Median time to discontinuation of RT was significantly longer for tadalafil OaD and PRN (130 and >168 days) compared with sildenafil (67 days) (HR [97.5% confidence interval]: 0.66 [0.51, 0.85] and 0.49 [0.37, 0.65]; P < 0.001). Reasons for discontinuation with significant differences between groups (P < 0.05) included "lack of efficacy (duration of erection)" (sildenafil 9.2% vs. tadalafil OaD 4.3%, PRN 2.8%), "time constraints due to short window of action" (sildenafil 4.2% vs. tadalafil OaD 0%, PRN 0.4%), and "feel medication controls my sexual life" (sildenafil 2.7% vs. tadalafil OaD 0%). No between-group differences were found in International Index of Erectile Function-Erectile Function domain change from baseline to end of RT (least squares mean: 9.4-10.0, P = 0.359) or discontinuations due to adverse events (1.2-1.6%). The most common adverse event (≥ 4%) was headache.
  
  
  CONCLUSIONS
  ED patients assigned to tadalafil OaD or PRN adhered significantly longer to initial treatment than patients assigned to sildenafil PRN. Improvement of erectile function and safety profiles were similar in all three treatment groups.
authors.affiliation: Centre d'Etude et de Traitement de la Pathologie de l'Appareil Reproducteur et de la Psychosomatique (Centre ETPARP), Lille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Buvat
authors.forename: Hartwig
authors.initials: H
authors.lastname: Büttner
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Hatzimouratidis
authors.forename: Pedro A S
authors.initials: PA
authors.lastname: Vendeira
authors.forename: Ignacio
authors.initials: I
authors.lastname: Moncada
authors.forename: Michael
authors.initials: M
authors.lastname: Boehmer
authors.forename: Carsten
authors.initials: C
authors.lastname: Henneges
authors.forename: Frank G
authors.initials: FG
authors.lastname: Boess
mesh_terms: D000328:Adult; D000368:Aged; D002243:Carbolines / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D057915:Drug Substitution; D007172:Erectile Dysfunction / Q000188:drug therapy*; D005060:Europe; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D017060:Patient Satisfaction; D010410:Penile Erection / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects; D020127:Recovery of Function; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects; D000068581:Tadalafil; D016896:Treatment Outcome
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068581:Tadalafil; D000068677:Sildenafil Citrate