Alpha Blockers Aid Passage of Large Ureteric Stones

For every 1 mm increase in stone size, the odds of passage increased by 9.8%.
For every 1 mm increase in stone size, the odds of passage increased by 9.8%.

Medical expulsive therapy with alpha blockers can promote clearance of ureteric stones 5 mm and larger, a new systematic review and meta-analysis confirms. 

“These results support current guideline recommendations advocating a role for alpha blockers in patients with ureteric stones,” John M. Hollingsworth, MD, MS, of the University of Michigan in Ann Arbor, and colleagues stated in the British Medical Journal.

The investigators reported a 49% greater likelihood of ureteric stone passage with an off-label alpha blocker compared with no treatment or placebo. Treated patients with stones 5 mm or larger had a 57% greater likelihood of stone clearance. The study revealed no treatment benefit for patients with smaller ureteric stones. Given that ureteric stones smaller than 5 mm pass easily without treatment, this finding was unsurprising, according to the investigators.

For their updated meta-analysis, the team pooled data from 55 randomized controlled trials of moderate quality involving 5990 patients published up to July 2016. Although tamsulosin was the most commonly studied medication, they observed no significant differences with other alpha blocker medications, such as alfuzosin, doxazosin, naftopidil, silodosin, or terazosin.

Stone location—either lower, middle, or upper ureter—had no bearing on results. Alpha adrenergic receptors are concentrated in the lower ureter but they exist along the entire ureter, the investigators highlighted.  

Stone passage occurred at 8.8 and 13.3 days on average in the treatment and control groups, respectively. Stone passage occurred 3.79 days sooner among patients who received alpha blockers compared with those who received no treatment or placebo. Treated patients also enjoyed fewer episodes of pain and lower risks of surgical interventions and hospitalizations.

Few serious adverse events were reported and were similar between treated and control patients.

A 2015 Lancet study (25;386(9991):341-349) by Robert Pickard, MD, and colleagues had questioned the benefit of off-label alpha blocker use and drew concern from the urologic community. It found no difference between medical expulsive therapy and placebo. However, a high rate of spontaneous stone passage among controls might explain the results, according to the researchers of the current review. Radiologic testing results, they added, would have been more revealing than that study's endpoint: no further intervention following drug treatment. 

“Given the low risk profile of these drugs and their wide therapeutic window, our findings suggest that clinicians who manage patients with ureteric colic should consider prescribing a course of an alpha blocker, unless it is medically contraindicated,” Dr Hollingsworth and colleagues concluded. The investigators estimated that 4 patients would need to be treated for 1 patient to see a benefit.

Reference

1. Hollingsworth JM, Canales BK, Rogers MAM, Sukumar S, Yan P, Kuntz GM, and Dahm P. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ 2016; 355 doi: http://dx.doi.org/10.1136/bmj.i6112.

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