Tamsulosin ineffective for kidney stones??? Not so fast...

​A recent article suggested that tamsulosin was ineffective in improving kidney stone passage, for stones up to 9mm (see kidney stone tamsulosin not help jamaintmed in dropbox, or doi:10.1001/jamainternmed.2018.2259)

Details:

-- 497 patients with symptomatic urinary stones <9 mm in diameter, lodged in the ureter as demonstrated by CT scanning, were randomized to tamsulosin 0.4 mg vs placebo for 28 days, from 2012 to 2016

-- mean age 41, 27% female, 23% nonwhite, 30% personal history of kidney stones, 25% family history of kidney stones, 69% of the stones were in the distal ureter or ureterovesical junction

-- stone size: 18% were 1-2 mm, 56% 3-4 mm, 21% 5-6 mm, 5% 7-8 mm (mean diameter 3.8 mm); hydronephrosis on CT in 74%, multiple stones in 38%

-- primary outcome was stone passage based on CT visualization or capture by the study participant by day 28

Results:

-- stone passage rates were 49.6% in the tamsulosin group vs 47.3% in the placebo group, RR 1.05 (0.87-1.27), nonsignificant difference

-- no difference in the secondary outcomes of: crossover to open-label tamsulosin, time to stone passage, return to work, use of analgesics, hospitalization, surgical intervention, and repeated ED visits

-- subgroup analysis: no difference in outcomes by history of prior stone, males vs females, age, stone location

-- post-hoc analysis: no difference by stone size and location, "though low power for all statistical tests of interaction"

-- no difference in treatment-related adverse effects, other than increased ejaculatory dysfunction in men on tamsulosin (18.2% vs 7.4%)

Commentary:

-- urinary stones are really common, affecting roughly one in 11 people over their lifetime in the United States, with an annual medical cost of $5 billion
-- the prevalence of urinary stones has doubled in the past 15 years, attributed largely to increases in diabetes, obesity, metabolic syndrome.
-- ED visits have doubled over the period of 1992-2009 from 178 to 340 visits per 100,000
-- the current US Urologic Association guidelines strongly recommend that patients with ureteral stones 10 mm or less be offered alpha blockers to promote stone passage
-- a review of some of the recent literature shows:
    -- a recent systematic review/meta-analysis of 55 RCTs did find that there was moderate quality of evidence that a-blockers were helpful in facilitating stone passage, with RR 1.49. However, this was only true for stones >5mm in diameter: those with these larger stones had a 57% higher likelihood of stone passage vs controls. This effect on stone passage was independent of stone location (see kidney stone alpha blockers review bmj2016 in dropbox)
    --an even more recent Chinese study found that in 3450 patients with distal ureteral stones in 30 centers, tamsulosin 0.4mg/d vs placebo was associated with 86% vs 79% stone expulsion rate, with a specific benefit in those with stones >5mm. there was also a shorter time to expulsion of the stone, lower use of analgesics and decreased renal colic. (see Ye Z. Europ Urol 2018; 73: 385-91, or doi.org/10.1016/j.eururo.2017.10.033 0302-2838) [note that this study was about 7 times larger than the current study.]
    -- However, the authors of the current study commented on two other studies which they stated supported their conclusion of lack of benefit.  An Australian study of 403 patients, for which they reported that there was no difference in active treatment with tamsulosin, in fact noted that in the subgroup with stones between 5 and 10 mm, “tamsulosin did increase passage and should be considered”. And, a second study from the UK comparing nifedipine vs tamsulosin vs placebo, did in fact find a trend to benefit of tamsulosin (on the order of 2-fold) in those with stones greater than 5 mm, though only 94 patients were in the tamsulosin group, which may well have been the reason for lack of statistically significant benefit.
    -- By the way, the authors of the current study also actually lumped the above large Chinese study (which showed benefit in large stones) in with these 2 studies as calling into question the Am Urologic Assn guidelines....
--the authors do note that "our study was not designed to detect a treatment effect of tamsulosin in subgroups based on stone size. [i would argue here that small stones probably do not need much help to pass on their own, as confirmed in pretty much everything i've seen; their study was pretty small and had very few patients with stones >5mm (which clearly limits the study generalizability); and, they seem to have distorted the literature a bit to justify their global conclusion about stones up to 9mm in size]

So, the conclusion of the study was “our findings do not support the use of tamsulosin for symptomatic urinary stones smaller than 9 mm. Guidelines for medical explosive therapy for urinary stones may need to be revised”. However, as above, i do not believe their study justifies this conclusion, specifically for stones 5mm and larger.

I bring up this article for 2 reasons:
-- it is pretty common in primary care to have patients present with lots of pain from kidney stones. Most patients with stones can be treated without urologic intervention, and the conclusion of this article undercuts utility of what seems to be an important and pretty safe medical intervention, which might decrease surgical interventions and at the same time improve patients' pain and function.
-- and this kind of article really brings up a general major concern in reading the medical literature: we are inundated with so many articles, many of which could affect our clinical practice, that in most cases we do not have the time or energy to dig a little deeper and look at the actual study. In this case, they overinterpreted the most important conclusion (ie, they had no real evidence that treating larger stones was ineffective), and they distorted their review of prior literature to bolster their conclusion. Makes it hard to accept the one-liner conclusions of potentially useful important studies, and this problem can be even more complicated when the conclusions of the study reaches the general public (most often prior to our having a chance to look at it....)

geoff

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