Hypothesis / aims of study
Nocturia impairs quality of life (QoL) and is one of the most bothersome lower urinary tract symptoms (LUTS). Treatments such as α1-adrenoceptor antagonists, muscarinic receptor antagonists or β3-adrenoceptor agonists had only limited impact on nocturia in placebo-controlled trials despite being effective against other LUTS and overall QoL . One theory to explain this discrepancy is that nocturia is a multifactorial symptom and that reducing one of its causes is insufficient to cause major improvements of nocturia. Therefore, a non-interventional study had been designed to explore effects of tamsulosin OCAS on nocturia-related QoL and factors associated with nocturia-related QoL at baseline and upon treatment.
Study design, materials and methods
A non-interventional study enrolled 5775 mean with LUTS to systematically follow patients who had received a prescription of tamsulosin OCAS based on the judgment of their urologist. Outcome parameters were IPSS and the nocturia-related QoL as assessed by a validated tool, the NQoL score and its sleep and bother subdomains . Additionally, we captured presence of several known causes of nocturia including fluid intake (<1, 1-2 and >2 l/day), alcohol consumption on day before visit (yes/no), previous diagnosis of heart failure, diabetes or sleep apnea.
All data analyses had been defined in a statistical analysis plan prior to completion of the study. The primary outcome parameters were NQoL at baseline and treatment-associated changes thereof. Data were analyzed descriptively and are reported as means ± SD or as % of subjects. Moreover, we performed general linear models to explore the effects of various explanatory variables on baseline values and treatment-associated changes thereof. To compare the direct effects of non-urological causes and those occurring secondary to their effect on nocturnal voids, all models were run with and without inclusion of nocturia episodes as explanatory variable. Calculations were performed using the SAS program package (version 8.2.; SAS Institute, Cary, NC, USA). All reported p-values should be interpreted as descriptive only.
Participants had a mean age of 66 ± 9 years. The comorbidities of heart failure, diabetes or sleep apnea were noted in 15.3%, 21.0% and 1.7% of patients, respectively. Concomitant use of diuretics and hypnotics was reported in 11.4% and 2.6% of patients, respectively. Small (< 1 l), medium (1-2 l) and high fluid intake (> 2 l) was reported in 7.2%, 72.9% and 18.6% of patients. Use of alcoholic beverages on the evening prior to the office visit was reported by 24.0% of patients. Treatment with tamsulosin OCAS was associated with clinically meaningful changes of IPSS, number of nocturnal voids, Qmax, post-void residuals, QoL (from IPSS score) and total NQoL and its subdomains (Table 1).
At baseline, age, comorbidities, fluid intake and number of nocturnal voids were associated with total NQoL but effect sizes were small, for instance heart failure accounting for 3.5 and diabetes for 3.8 NQoL points; when number of nocturnal voids was included in the model, these differences became even smaller (Table 2).
Similar analyses for treatment-associated improvements of NQoL or its subdomains yielded similar outcomes with regard to explanatory variables. Notably, effect sizes also became smaller when number of nocturnal voids was included into the model.
Interpretation of results
Comorbidities and other known causes of nocturia have only moderate impact on NQoL at baseline and treatment-associated improvement thereof in male LUTS. This impact becomes even smaller when number of nocturnal voids is part of the analytical model, indicating that they contribute to NQoL directly and indirectly, i.e. by increasing number of nocturnal voids.