Previous clinical studies indicate that tadalafil, phosphodiesterase 5 inhibitor, is less efficacious in elderly patients. However, there are few clinical studies about the persistence rate among men treated with tadalafil for lower urinary tract symptoms (LUTS). Thus, we examined the persistence rate with tadalafil in men with LUTS and explored the influencing factors on the withdrawal.

We retrospectively collected the data of patients who received tadalafil treatment for LUTS. The persistence rate and the reason for the withdrawal were investigated. Influencing factors on the withdrawal were analyzed with regard to patient’s age, severity of symptoms, prostatic volume (PV), the prescription by the specialized or general urologist, drug-naïve patients, replacement of or add-on therapy to other agents for LUTS.

A total of 155 male patients were examined for this study. Mean age and observation period were 71.9 (48 – 93) years old and 15.1 (1 – 52) months, respectively. One hundred eleven patients (72%) had any coexisting medical conditions such as hypertension, diabetes or hyperlipidemia. The mean number of medicines for other diseases was 3.9 (0-20). In 29 patients (18%), tadalafil was used as a replacement for other agents for LUTS, and in 63 patients (41%), tadalafil was combined with other agents for LUTS. Eventually, 74 patients (48%) withdrew tadalafil during the observation period. The persistence rate at one year was 58%. The main reasons for withdrawal included insufficient efficacy (31 patients, 42%), adverse events (AEs) (21 patients, 28%), or symptom improvement (8 patients, 11%). 
When excluding those patients who withdrew tadalafil due to AEs and symptom improvement, the persistence with tadalafil was significantly related only with age. Number of existing diseases or medicines for other diseases was not correlated with the persistence with tadalafil. A receiver operating characteristic (ROC) curve analysis confirmed 67 years old as the best cut-off age for the withdrawal (area under the curve=0.599). Kaplan-Meier method indicated the persistence rate at one year in patients < 67 years old and ≥ 67 years old were 82% and 65%, respectively (p<0.05, Figure). No influencing factors on the persistence rate were detected by the multivariate method.

To our knowledge, this is the first report on the persistence rate with tadalafil for treatment of male LUTS. The function of NO/cGMP pathway, a main target of tadalafil, is reported to decline with aging. A meta-analysis of clinical efficacy of PDE5 inhibitor on LUTS shows that improvement of LUTS by PDE5 inhibitor is depended on age and body mass index; better in younger age and less obese patients [1]. Thus, aging seems to have a significant impact on the efficacy of tadalafil. It was reported that the improvement with tadalafil in patients over 65 years was not statistically significant compared with that of placebo-treated patients [2]. Similarly, it was showed that the efficacy of once-daily tadalafil 5 mg in the treatment of LUTS was better in men aged under 75 years than men over 75 [3].

Main reason for discontinuing tadalafil was insufficient efficacy. Older patients are more likely to discontinue tadalafil treatment. It seems that tadalafil for male LUTS is more effective for younger patients and better persistence is expected in them.

Gacci M, et al. Eur Urol 2012; 61: 994-1003
Nishizawa O, et al. Int J Urol. 2015; 22: 378-84.
Oelke M, et al. BJU Int. 2017; 119: 793-803.