Improvement in symptoms following 6 week alpha-blocker use and predictors of improvement: A single-arm open-label cohort study in clinical practice.

van der Worp H1, Kollen B1, Vermist T1, Steffens M2, Blanker M1

Research Type

Clinical

Abstract Category

Male Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction

Abstract 556
E-Poster 3
Scientific Open Discussion ePoster Session 31
Friday 6th September 2019
13:25 - 13:30 (ePoster Station 1)
Exhibition Hall
Male Prospective Study Benign Prostatic Hyperplasia (BPH) Pharmacology
1.University Medical Center Groningen, Department General Practice and Elderly Care Medicine, 2.Isala Clinics Zwolle, Department of Urology
Presenter
M

Marco H Blanker

Links

Poster

Abstract

Hypothesis / aims of study
Trials that study the effect of alpha-blockers on LUTS in general report mean changes in symptom scores. This may be problematic for both patients and clinicians. Patients won’t recognise the exact impact on symptom scores but instead summarize the subjective change as successful or not. Next, clinicians would like to know how many patients benefit from treatment. Given the multifactorial origin of LUTS, they are unable to determine who will respond to alpha-blocker treatment. To address the aforementioned problems, we have conducted an open label study. Our first aim was to assess the number of subjects that experienced symptom improvement following alpha-blocker use in daily practice. Our second aim was to find predictors of this improvement.
Study design, materials and methods
We performed an open-label single-arm observational cohort study with a six-week follow-up. Patients visiting the pharmacy with a prescription from a general practitioner (GP) or urologist were eligible for inclusion, if the alpha-blocker was prescribed for LUTS (and not nephrolithiasis or indwelling catheter use), and no earlier prescriptions were present in the preceding year. At baseline, all men completed a short questionnaire containing the IPSS and OABq-SF. After six weeks, irrespective of the actual usage of the alpha-blocker at that point in time, men completed a second questionnaire with IPSS, OABq-SF and the Patient Global Impression of Improvement (PGI-I). The prescriber completed a short questionnaire and the pharmacist provided information on concomitant drug usage.
PGI-I was the main outcome, and we categorized the responses ‘much better’ or ‘very much better’ on this question as clear improvement and all other categories as no clear improvement. Demographic, disease related and drug related information was used to identify predictors of clear improvement using logistic regression analyses. Linear regression analyses were performed with change in IPSS and OAB-q as outcomes. First univariate regression was performed. Variables with a p-value <0.25 were subsequently included in multivariable regression analyses using a non-automated step-wise forward selection strategy. Analyses were performed on both original data and on imputed data. We performed a subgroup analysis that only included patients that received their prescription from a GP, to allow interpretation for primary care.
Results
Of 258 subjects with a new alpha-blocker prescription screened, 251 men met the inclusion criteria of which 248 subjects participated in the study. Complete data was obtained for 119 cases. Men were on average 66.3±9.3 years, had a IPSS of 19.4±6.8 and an OABq-SF score of 39.7±19.9. 
Of all men, 37% reported clear improvement after six weeks. In the analyses on original data, the current use of alpha-blockers (univariate OR 5.31 95% CI 1.71;16.47 and multivariate OR 5.70 95% CI 1.73;18.84) and the use of six or more co-medications (univariate OR 3.89 95% CI 1.35;11.25 and multivariate OR 3.80 95% CI 1.23;11.70) predicted clear improvement in both univariate  and multivariate analyses. Imputed data analyses yielded no significant predictors of clear improvement. The subgroup analysis on patients with a prescription of a GP showed that also 37% reported clear improvement. In this subgroup patients with symptoms for over 24 months were less likely to show clear improvement compared to those with symptoms for less than 6 months (OR 0.36 95% CI 0.13;0.98). Regression analyses with IPSS and OABq-SF as de dependent variable only identified pre-treatment symptom scores as predictors of change.
Interpretation of results
In the studied cohort one in three patients with LUTS perceived clear symptom improvement as measured with the PGI-I six weeks after the start of an alpha-blocker. Predictors of clear improvement were the current use of alpha-blockers and the use of six or more co-medications, but only in the model based on the original data. However, odds ratios in the analysis on imputed data showed a similar trend. The increased odds for current use indicates that subjects that still used alpha-blockers after six weeks were more likely to experience clear improvement. Such a relationship was not found between current use of alpha-blockers and more objective measures of improvement as the IPSS and OABq-SF indicating that the improvement could not be attributed to changes in for example frequency of urination of episodes of incontinence. An explanation for the increased odds for subjects that took more types of medication may be that drug adherence is related to concomitant use of other types of medication. So subjects that took more types of medication may have been more adherent to alpha-blockers. The present study didn’t monitor actual intake though. Prescribing alpha-blockers by GPs for patients that have symptoms for over 24 months seems less effective.
Concluding message
In our study population the probability of perceiving clear improvement after receiving an alpha-blocker was 37%. This number can be used by clinicians to inform patients. However, this study does not provide much guidance for clinicians on which patients benefit most from alpha-blocker treatment. As such, the primary care approach in the treatment of male LUTS remains a trial with continuation of treatment in case of clear symptom improvements.
Disclosures
Funding Hein Hogerzeil Foundation Clinical Trial No Subjects Human Ethics Committee Medical Ethical Committee of the University Medical Center Groningen (METc 2016.122) Helsinki Yes Informed Consent Yes