Adherence to Initial PDE5 Inhibitor Treatment: Randomized OpenLabel Study Comparing Tadalafil Once a Day, Tadalafil on Demand, and Sildenafil on Demand in Patients with Erectile Dysfunction

Abstract Introduction Phosphodiesterase type 5 (PDE5) inhibitor treatment for erectile dysfunction (ED) is frequently discontinued; adherence may vary depending on the initial regimen. Aim 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, openlabel study, men (≥18 years) with ED, naive to PDE5 inhibitors, were randomized (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8week randomized treatment (RT) period (dose adjustment possible) was succeeded by 16 weeks of pragmatic treatment (switches between PDE5 inhibitors allowed). Main Outcome Measures Treatment adherence was measured as time to discontinuation of RT (any cause), estimated by Kaplan–Meier productlimit method. Treatmentgroup 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 P 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.