Progression of Lower Urinary Tract Symptoms After Discontinuation of 1 Medication From 2-Year Combined Alpha-blocker and 5-Alpha–reductase Inhibitor Therapy for Benign Prostatic Hyperplasia in Men – A Randomized Multicenter Study

doi:10.1016/j.urology.2013.09.036

Urology

Volume 83, Issue 2, February 2014, Pages 416-421

https://doi.org/10.1016/j.urology.2013.09.036 Get rights and content

Objective

To investigate the treatment outcome of discontinuing 1 medication from 2-year combination therapy for male benign prostatic hyperplasia/lower urinary tract symptoms.

Materials and Methods

Patients with International Prostate Symptom Score ≥8, total prostatic volume (TPV) >30 mL, and maximum flow rate (Qmax) <15 mL/s were randomly assigned to the 5α-reductase inhibitor (5ARI) discontinue (DC-5ARI) or α-blocker discontinue (DC-α-blocker) group. All patients received combination therapy with dutasteride (0.5 mg QD) and doxazosin (4 mg QD) for 2 years and then discontinued either one drug for 12 months. The primary endpoint was the occurrence of resuming medication. The secondary endpoints were the net parameters changed or the need of transurethral resection of the prostate (TURP).

Results

A total of 117 patients in DC-5ARI and 113 in DC-α-blocker group completed the study. The baseline TPV and Qmax were similar between groups before combination therapy. Resumption of combination therapy was significantly more in DC-5ARI than DC-α-blocker group (51.3% vs 31.0%; P = .005). The mean duration from discontinuing to resuming medication was 5.0 ± 4.4 months in DC-α-blocker and 7.8 ± 3.8 months in DC-5ARI group (P <.05). The TPV progression (29.1% vs 8.0%; P <.001) and the need for TURP (14.5% vs 7.1%; P = .043) were significantly higher in DC-5ARI than DC-α-blocker group. Patients with larger TPV (45.8 ± 18.1 mL) had significantly greater need for resuming 5ARI than smaller TPV (36.3 ± 16.9 mL; P = .007), and a lower Qmax might predict resuming α-blocker.

Conclusion

After a 2-year combination therapy, discontinuation of either one drug induced benign prostatic hyperplasia progression in either group. Greater risk of resuming medication and needing TURP were noted in patients who discontinued 5ARI.

Section snippets

Materials and Methods

This study was a prospective, randomized, multicenter, open-labeled, comparative study in men aged at least 45 years with symptomatic BPH. The inclusion criteria were moderate-to-severe LUTS with an International Prostate Symptom Score (IPSS) >8, quality of life index (QoL-I) >4, TPV >30 mL by transrectal ultrasonography (TRUS) of the prostate, and maximum flow rate (Qmax) <15 mL/s with minimal voided volume ≧125 mL. If patients had serum prostate-specific antigen (PSA) ≧4 ng/mL, TRUS-guided

Results

The total enrolled patients were 240 who were randomized to 120 in DC-5ARI and 120 in DC-α-blocker groups, respectively. Patient disposition is shown in Figure 1. During the stage 1 period (from baseline to 2-year combination therapy), 3 DC-5ARI and 7 DC-α-blocker patients withdrew from the trial because of ineffective treatment result. The other patients (117 patients in DC-5ARI group and 113 in DC-α-blocker group) were continued through stage 2 study (from discontinuation medication till the

Comment

Our study confirmed that combination therapy for 2 years is effective in improving LUTS in men with LUTS/BPH. After 2-year combination therapy, discontinuation of either one medication induced progression of LUTS or uroflow parameters in most of the patients. The rate of clinical BPH progression at 1 year after discontinuing either medication in our study was higher than the rate of clinical BPH progression (12.6%) after a 4-year combination therapy.⁸ The rate of TPV progression, resumption of

Conclusion

Randomly discontinuing 1 medication from combination therapy for 2 years was associated with BPH progression in either group that needs to resume combined medication or surgical intervention in DC-5ARI or DC-α-blocker group. Greater risk of resuming medication and needing TURP was noted in patients who discontinued 5ARI. Progression of TPV and PSA after discontinuing 5ARI was remarkable but did not affect the treatment outcome in patients with smaller BPH after combination therapy for 2 years.

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Room for improvement in reporting of trials discontinuing long-term medication: a systematic review
2020, Journal of Clinical Epidemiology
Discontinuation of inappropriate medication is widely recognized as an essential component of best prescribing practice. Physicians typically attempt to taper or stop medications on the basis of clinical experience, rather than using a systematic approach guided by evidence. We sought to evaluate if the reporting of deprescribing trials conducted in primary care is of sufficient quality and detail to allow replication in clinical practice.
This study presents a secondary analysis of data from a systematic review published in 2018, investigating the effects of discontinuation of chronic medication in primary care. Twenty-six publications reporting on 27 trials were included. The quality of reporting was assessed using the Template for Intervention Description and Replication (TIDieR) checklist.
No study provided complete reporting on all TIDieR items. All studies provided a clear description and rationale for the intervention; however, details of the intervention were insufficiently reported in most studies, with high variability between studies. Consultation of secondary sources resulted in minimal additional information.
There are significant deficits in reporting methodological details of deprescribing interventions in primary care. It is likely that evidence-based deprescribing is not being implemented as routinely into health-care practice as it could be. Increasing the quality of intervention reporting is essential to avoid wastage of research resources and ought to be a focus for all discontinuation trials.
Systematic Review of Combination Drug Therapy for Non-neurogenic Lower Urinary Tract Symptoms
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Citation Excerpt :
The results showed that the combination therapy, dutasteride monotherapy, and tamsulosin monotherapy all improved Qmax but to different extents (combination therapy > dutasteride ≫ tamsulosin), suggesting that dutasteride contributes most to the Qmax benefit in combination therapy [22]. In 2014, Lin et al. [23] investigated the treatment outcome of discontinuing one medication from 2-yr combination therapy for male with BPH/LUTS. Patients were randomly assigned to the 5-ARI discontinue (DC-5ARI) or the α-blocker discontinue (DC-α-blocker) group.
Several drugs are approved and available for the treatment of lower urinary tract symptoms (LUTS) in men and women. However, the vast majority of available data, upon which the approval and recommendation in guidelines are based, considered only the role of the monotherapies and did not evaluate possible combination therapies.
This systematic review analyzes the efficacy and adverse events of combination therapies for male and female LUTS.
A systematic literature search in the PubMed/Medline, Web of Science, and Cochrane databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement to identify clinical trials, randomized controlled trials, meta-analyses, and guidelines on male and female LUTS combination therapy published from March 2012 to December 2017 for men (in order to update a previous men-focused work) and from January 1988 to December 2017 for women. A total of 58 papers were identified.
The most studied combination therapy for the treatment of male LUTS is the α1-adrenoceptor antagonist/5α-reductase inhibitor combination. This combination seems to be more efficacious in terms of several outcome variables, in particular in men who have moderate-to-severe LUTS and are at risk of disease progression. Also in terms of nocturia improvements, this combination is significantly more effective than the monotherapy. The other often studied combination treatment, in both male and female patients with LUTS, was the combination of antimuscarinics (in particular solifenacin) and mirabegron. This combination seems to be more effective in comparison with the monotherapies with respect to urinary incontinence and urgency urinary incontinence episodes and several other objective and subjective parameters, without relevant increase of adverse events. The combination of hormone therapy and antimuscarinics in women with LUTS does not seem to be useful.
For the treatment of LUTS in men and women, combination therapy appears to be a promising option to optimize the efficacy of the available drugs for those who do not experience sufficient benefit with monotherapy. This add-on scenario offers the possibility to have a more tailored approach to the management of LUTS, always seeking the optimal balance between efficacy and tolerability for a given patient.
Some combination of drugs may offer advantages over monotherapies for the treatment of voiding and storage complaints in men and women.
Deprescribing in older people
2016, Maturitas
Older people with chronic disease have great potential to benefit from their medications but are also at high risk of harm from their medications. The use of medications is particularly important for symptom control and disease progression in older people. Under-treatment means older people can miss out on the potential benefits of useful medications, while over-treatment (polypharmacy) puts them at increased risk of harm. Deprescribing attempts to balance the potential for benefit and harm by systematically withdrawing inappropriate medications with the goal of managing polypharmacy and improving outcomes. The evidence base for deprescribing in older people is growing. Studies to reduce polypharmacy have used a range of methods. Most evidence for deprescribing relates to the withdrawal of specific medications, and evidence supports attempts to deprescribe potentially inappropriate medicines (such as long-term benzodiazepines). There is also evidence that polypharmacy can be reduced by withdrawing specific medications using individualised interventions. More work is needed to identify the sub-groups of older people who may most benefit from deprescribing and the best approaches to undertaking the deprescribing interventions.
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Clinical outcomes of withdrawing one medication from long-term combination therapy comprising α-blocker and 5α-reductase inhibitor for benign prostatic hyperplasia
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Outcomes of dutasteride discontinuation in patients with benign prostatic hypertrophy
2022, Archivio Italiano di Urologia e Andrologia

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: Financial Disclosure: The authors declare that they have no relevant financial interests.

: Victor C. Lin and Chung-Hou Liao contributed equally.

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Prostatic Diseases and Male Voiding DysfunctionProgression of Lower Urinary Tract Symptoms After Discontinuation of 1 Medication From 2-Year Combined Alpha-blocker and 5-Alpha–reductase Inhibitor Therapy for Benign Prostatic Hyperplasia in Men – A Randomized Multicenter Study

Objective

Materials and Methods

Results

Conclusion

Section snippets

Materials and Methods

Results

Comment

Conclusion

Urology

J Urol

Eur Urol

Eur Urol

Eur Urol

Urology

Prostatic Diseases and Male Voiding Dysfunction
Progression of Lower Urinary Tract Symptoms After Discontinuation of 1 Medication From 2-Year Combined Alpha-blocker and 5-Alpha–reductase Inhibitor Therapy for Benign Prostatic Hyperplasia in Men – A Randomized Multicenter Study