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Article of the Week: Comparison of the efficacy and safety of tolterodine 2 mg and 4 mg combined with an alpha-blocker




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Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Tae Heon Kimdiscussing his paper. 

If you only have time to read one article this week, it should be this one.

Comparison of the efficacy and safety of tolterodine 2 mg and 4 mg combined with an alpha-blocker in men with lower urinary tract symptoms (LUTS) and overactive bladder: a randomized controlled trial

Tae Heon Kim*, Wonho Jung†, Yoon Seok Suh*, Soonhyun Yook‡, Hyun Hwan Sung* and Kyu-Sung Lee*‡
*Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, †Department of Urology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, and ‡Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea Tae Heon Kim and Wonho Jung contributed equally to this work.

 

Objective
To evaluate the efficacy and safety of low-dose (2 mg) tolterodine extended release (ER) with an a-blocker compared with standard-dose (4 mg) tolterodine ER with an α-blocker for the treatment of men with residual storage symptoms after α-blocker monotherapy.
Patients and Methods
The study was a 12-week, single-blind, randomized, parallel group, non-inferiority trial that included men with residual storage symptoms despite receiving at least 4 weeks of α-blocker
treatment. Inclusion criteria were total International Prostate Symptom Score (IPSS) ≥12, IPSS quality-of-life item score ≥3, and ≥8 micturitions and ≥2 urgency episodes per 24 h. The primary outcome was change in the total IPSS score from baseline. Bladder diary variables, patient-reported
outcomes and safety were also assessed.
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Results
Patients were randomly assigned to addition of either 2 mg tolterodine ER (n = 47) or 4 mg tolterodine ER (n = 48) to α-blocker therapy for 12 weeks. Patients in both treatment groups had a significant improvement in total IPSS score (5.5 and 6.3, respectively), micturition per 24 h (1.3 and
1.7, respectively) and nocturia per night (0.4 and 0.4, respectively). Changes in IPSS, bladder diary variables, and patient-reported outcomes were not significantly different between the treatment groups. All interventions were well tolerated by patients.
Conclusions
These results suggest that 12 weeks of low-dose tolterodine ER add-on therapy is similar to standard-dose tolterodine ER add-on therapy in terms of efficacy and safety for patients experiencing residual storage symptoms after receiving α-blocker monotherapy.

 

  1. Mike Kirby
    This paper is about choosing the right drug, right time for the right patient, but are we missing a trick??
    There is growing evidence that many urological conditions can be linked to metabolic syndrome, which in turn is linked to premature cardiovascular disease if not addressed.
    Patients presenting with LUTS may offer a ‘gateway’ to improving their wider health Assessment of risk factors and identifying features of metabolic syndrome gives physicians the opportunity to intervene to reduce the future risk of serious health problems, such as CVD morbidity and mortality, and diabetes LUTS have traditionally been attributed to progressive prostatic overgrowth, but recent studies suggest that metabolic derangements may affect the development of BPH, prostate growth and LUTS worsening, Emerging evidence in the relationship between metabolic syndrome and prostate growth suggests that modifiable factors, should be investigated as new targets for disease prevention, diagnosis and treatment of LUTS.

    For example:
    Men with ≥3 components of the metabolic syndrome have an increased risk of LUTS
    Odds ratio = 1.8
    History of diabetes or hypertension is particularly associated with LUTS
    Odds ratio of 1.67 and 1.76, respectively
    In diabetic men, the risk of LUTS increases with increasing HbA1c
    Severity of LUTS related to BPH is also associated with metabolic syndrome
    Risk of being treated for LUTS also increases with an increasing number of metabolic syndrome components
    Severity of LUTS related to BPH is also associated with metabolic syndrome
    Men with moderate-to-severe LUTS related to BPH also have a >5-fold increase of having a CVD risk score of ≥10%
    Insulin resistance shown to be an iIndependent predictor of severe LUTS (IPSS ≥20)
    Odds ratio = 2.0, P43,000 men from 11 studies found that exercise intensity was related to the reduction of prostate enlargement
    The risk of BPH or LUTS was significantly reduced for men engaging in light, moderate and heavy physical activity vs the sedentary group
    Odds ratio = 0.70, 0.74 and 0.74, respectively)
    Previous reports of increased LUTS with increasing body-mass-index suggest a stronger relationship with storage than with voiding symptoms and Increased levels of physical activity have consistently been associated with lower levels of LUTS
    A retrospective study of 2,447 men, aged 40–79 years found that statin use associated with a 6.5–7 year delay in the new onset of moderate/severe LUTS or BPH.
    The next LUTS study should be exercise & weight loss versus continuation of a sedentary lifestyle!
  2. Ian Dyer
    I think it was the famous doctor Maimonides who said that no disease that could be treated by diet should be treated by anything else. The issue for urologists is that there is growing evidence that the metabolic syndrome and insulin resistance is a significant cause of LUTS. I reported into Professor Kirby four years ago with, admittedly, not the worst symptoms of LUTS but still with some, and Mike, as I now know him, explained how drugs could be used to help. I didn't fancy those: it is plain that they deal with the symptoms, but not the causes of LUTS. Mike explained that there was potentially another way, but that few of his patients were willing to go for it: in simple terms, reduce one's BMI to 25 or so.

    I learned for the first time about the metabolic syndrome, which otherwise would have been a mystery to me, as it will be to many patients.

    Well, I said ok, I will give it a try, and within 6 months I had taken off 20 kilos and was doing a good deal of exercise - 20 miles a week, not a lot, but enough. I think based on my experience is that the exercise is as important as the weight loss.

    The result: all symptoms of LUTS disappeared. Was it a placebo effect? Who knows, but it worked. Was it that insulin resistance declined and this reduced LUTS. That's what Mike would say.

    Yes, of course, I am just one case. The trouble, of course, is that there are quite a few studies that BMI gain contributes to LUTS, but there are very few studies that show that BMI loss reduces or eliminates LUTS. Even Mike did not believe weight loss reduction could fully work.

    So I said to we should have study done on 100 men with LUTS, who go on a programme of diet and exericse and report what happens over a few months. It has not happened yet, but it should. It's cheap to run and monitor. It is a non invasive study and it can't really do the men who undertake it anything but good.

    My problem with the paper that has been published by these excellent doctors is that it is a bit mis-targeted. If LUTS can be diminished or eliminated by lifestyle changes, which have many other benefits, cardiovascular or otherwise, why would one want the drugs? A lifestyle approach will reduce the demand for TURPS etc, but that it no bad thing either. So I say that, before one tries a drug approach on a patient with LUTS, one should try an approach of a lifestyle change.

    We need, I think, a new vision of Urology that works more with the body and what the body is natrually attuned to do, and, while recognising the possible benefits of a surgical or pharmacological approach, puts them second to significant lifestyle changes in patient's lives, that not only diminish LUTS, but set them up for healthier and, on average, longer lives.

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