Many Men With LUTS Could Be Candidates to Stop Alpha-Blocker Treatment

More than a third of older men with lower urinary tract symptoms (LUTS) derived little or no benefit from an alpha-blocker and might be candidates for “deprescribing,” a small, randomized study suggested.

During active treatment in the crossover trial, 11 of the 30 patients had little or no symptom relief with the widely used alpha-blocker tamsulosin. An additional 11 had moderate improvement, and four patients could not tolerate the placebo run-in between assigned treatment periods, leaving only four patients (13.3%) who had strong benefits.

The findings suggest older men with LUTS and minimal benefit from tamsulosin might be “high-priority” candidates for treatment discontinuation or deprescribing, reported Scott R. Bauer, MD, of the University of California San Francisco, and colleagues in JAMA Network Open.

Additionally, the study provided evidence that an N-of-1 crossover trial design “can precisely quantify the individualized benefits and harms” of a treatment.

“Specifically, we demonstrated significant heterogeneity in treatment response and identified a significant proportion of participants that may benefit from discontinuing tamsulosin,” the authors concluded. “This study highlights the need to counsel patients on the heterogeneity of tamsulosin treatment effects and supports the clinical use of empiric tamsulosin trials rather than lifelong therapy. Larger studies are needed to confirm the generalizability across clinical settings and patient populations, to identify predictors of tamsulosin response, and to test the effect of N-of-1-guided deprescribing on clinical outcomes.”

The study added to a fairly limited volume of evidence on the issue of treatment discontinuation in LUTS. Several years ago, Dutch investigators performed a meta-analysis of 10 published studies evaluating discontinuation of alpha-blocker therapy. The data showed that discontinuing alpha-blocker monotherapy led to symptom worsening as compared with continuing treatment, but dropping the alpha-blocker from combination LUTS treatment did not.

The results also are in line with the Dutch group’s own study showing that about a third of patients with LUTS “perceived clear symptomatic improvement” when they initiated treatment with an alpha-blocker, but the data did not provide insight into the patients most likely to benefit.

The study by Bauer and colleagues “is a highly relevant study, that we would have liked to perform in the Netherlands, but were unable to receive funding for,” Marco H. Blanker, MD, PhD, of University Medical Center Groningen, told MedPage Today. “It is a great study that, with thanks to its design, was possible to conduct in a small number of participants. This is the impact of the N-of-1 design.”

“Although discontinuation of alpha-blocker therapy is advocated for in the Dutch guideline for male LUTS, in daily practice, the discontinuation rate is relatively small,” he added. “The study performed by Scott Bauer and colleagues, supports the rationale for discontinuation. In daily practice, a placebo-controlled setting is difficult, which may result in observing a placebo effect after discontinuation. In general, discontinuation of chronic drugs should be considered to minimize the potential negative influence of polypharmacy.”

Tamsulosin is the most widely prescribed medication for men with LUTS, Bayer and colleagues noted in their introduction. Despite the widespread use, alpha-blocker efficacy is modest and several studies have shown that many men who discontinue the drugs do not require additional treatment.

In addition to the modest benefits, alpha-blockers carry a risk of several notable adverse events, including orthostatic hypotension, dizziness, falls, and fractures, prompting recommendations for use with caution in older men. Moreover, LUTS has a dynamic natural history that includes spontaneous symptom resolution in a subset of men, the authors continued.

Given the lack of predictors of benefit for alpha-blockers, Bauer and colleagues evaluated the potential of N-of-1 trial design to achieve personalized, patient-centric care for older men with LUTS. They performed a series of double-blind, placebo-controlled N-of-1 deprescribing trials — multiple crossover trials — comparing tamsulosin and placebo in men on urologist-prescribed chronic tamsulosin for LUTS.

The 30 study participants had an age range of 55-80 and all had used tamsulosin continuously for at least 12 months. After a week-long placebo run-in, the men were assigned to two blocks of 2-week treatment periods, alternating tamsulosin and placebo, separated by 1-week washout periods.

Investigators used a modified version of the seven-item American Urological Association Symptom Index (AUA-SI, total score range 0-35) to assess efficacy. Effect size was categorized based on the upper bound of the individual 95% CI for the tamsulosin-placebo difference in daily AUA-SI, with minimal or no treatment effect defined as ≥0, moderate as >-6.0 to <0, and strong as ≤-6.0.

The results showed minimal or no effect of tamsulosin on symptoms in 36.7% of patients, moderate effect in 36.7%, and strong effect in 13.3%. The remaining four patients could not tolerate the 1-week placebo run-in because of worsening symptoms. On the basis of a mean of 54 daily AUA-SI assessments per study participant, the individual-level estimated mean difference in daily AUA-SI score between tamsulosin and placebo ranged from -10.9 to 2.1.