Alpha-blockers Do Not Promote Passage of Urinary Stones

Pam Harrison

June 19, 2018

A new trial adds to evidence that alpha-blockers do not expedite the passage of ureteral stones in patients who present with renal colic compared with placebo, although stone size may matter.

"Use of medical expulsive therapy for urinary stone disease in the setting of the emergency department is common, varying between about 15% and 55%," Andrew Meltzer, MD, associate professor of emergency medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, and colleagues write. "We found that compared with placebo, 28-day treatment with tamsulosin did not increase the overall stone passage rate or improve a wide range of secondary outcomes in patients who presented to the emergency department with symptomatic ureteral stones less than 9 mm in diameter," they add. "[G]uidelines that recommend tamsulosin for ureteral stones may need to be revised."

The study was published online June 18 in JAMA Internal Medicine.

The Study of Tamsulosin for Urolithiasis in the Emergency Department (STONE) was performed in 2 phases. Researchers carried out the first phase at a single site from 2008 to 2009. They recruited 109 patients who presented to the ED with symptomatic urinary stones confirmed by the use of computed tomography (CT) to be less than 9 mm in diameter and located in the ureter.

In the second phase, they enrolled patients from six EDs in the United States between 2013 and 2016.

The current analysis includes data from both phases of the study and includes 497 evaluable patients. "Eligible patients were randomized to either tamsulosin at a dose of 0.4 mg daily or a matching placebo," researchers observe.

Passage of the stone was determined by patients either visualizing the stone passing or capturing the stone once it had passed. The mean age of the cohort was 40.6 years, and the mean diameter of the stone that led to symptoms of renal colic was 3.8 mm.

At the end of the 28-day treatment period, the urinary stone passage rate, which was the primary trial endpoint, was 49.6% among participants assigned to tamsulosin vs 47.3% for placebo control patients, a difference that was not statistically significant (relative risk [RR], 1.05; 95% confidence interval [CI], 0.87 - 1.27; P = .60). Secondary end points including the time to stone passage, return to work, analgesic use, hospitalization, the need for surgery including lithotripsy, and repeated ED visits were also similar between the 2 treatment groups.

Table. Primary and Secondary Outcomes by Treatment Group Through 28 Days

  Tamsulosin Placebo Relative Risk (95% CI) Placebo
Patient reported stone passage 49.6% 47.3% 1.05 (0.87 - 1.27) 0.60
Stone passed on follow-up computed tomography 83.6% 77.6% 1.08 (0.95 - 1.22) 0.24
Surgery for urinary stone 6.5% 6.9% 0.95 (0.46 - 1.97) 0.89
Hospitalization resulting from stone 0.9% 0.5% 1.88 (0.17 - 20.34) >0.99
Return to work 99.0% 98.2% 1.00 (0.98 - 1.03) 0.67
Return to ED because of stone 2.2% 2.4% 0.93 (0.27 - 3.16) >0.99

Adverse Events

The researchers note that rates of ejaculatory dysfunction were higher, at 18.2%, in men who received tamsulosin compared with 7.4% for placebo control patients. Otherwise, there were no serious adverse events in either treatment group.

"A treatment that promotes the passage of urinary stones without the need for surgery could reduce both patient morbidity and health care costs associated with this condition," Meltzer and colleagues write.

"Our study, the largest clinical trial of medical expulsive therapy in the United States to our knowledge, found no difference in the overall 28-day urinary stone passage rate between participants who were treated with tamsulosin and those who received placebo," they continue.

"Although tamsulosin may still play a role in medical expulsive therapy for larger stones, guidelines that recommend tamsulosin for ureteral stones may need to be revised."

Results Parallel Prior Trial

In an accompanying editorial, Philipp Dahm, MD, from the University of Minnesota, Minneapolis, and John Hollingsworth, MD, from the University of Michigan, Ann Arbor, point out that the results from the current study parallel those from a previous multicenter, randomized trial from the United Kingdom involving more than 1100 patients with symptomatic ureteral stones, the Spontaneous Urinary Stone Passage Enabled by Drugs, or SUSPEND, trial. SUSPEND showed that medical expulsive therapy was not more efficacious at reducing rates of intervention for stone clearance at 4 weeks than placebo.

"We agree with Meltzer and colleagues that guideline recommendations on medical expulsive therapy should be revised," they write.

However, the editorialists suggest tamsulosin may help promote stone passage for larger stones up to 9 mm in size. Hollingsworth was the lead author on a systematic review and meta-analysis that showed that patients with larger ureteral stones treated with an alpha-blocker had a 57% higher rate of stone passage compared with controls (RR, 1.57; 95% CI, 1.17 - 2.27).

These findings indicate that although alpha-blockers may offer not benefit in patients with ureteral stones up to 5 mm in diameter, "emerging data suggest benefit in those with ureteral stones larger than 5 mm in size," Dahm and Hollingsworth state.

However, researchers who presented the results of a large observational study at the European Association of Urology (EAU) 2018 Congress earlier this year concluded that medical expulsive therapy had no benefit regardless of stone size.

The authors and the editorialists have disclosed no relevant financial relationships.

JAMA Intern Med. Published online June 18, 2018. Full text

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