Medical Expulsion Therapy with Tamsulosin or Nifedipine Does Not Increase the Rate of Spontaneous Stone Passage in Adults with a Single Ureteric Stone

EBM Focus - Volume 10, Issue 30

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Reference - Lancet 2015 July 25;386(9991):341 (level 1 [likely reliable] evidence)

Renal calculi occur in 5%-15% of the population worldwide (BMJ 2007 Mar 3;334(7591):468). Some stones may cause ureteral obstruction leading to severe and debilitating pain and are a common cause of emergency department visits (J Urol 2014 Jan;191(1):90). Patients with ureteral stones are often simply observed for stone passage, unless there is an indication for active removal, such as persistent obstruction, persistent pain unresponsive to pain medication, or renal insufficiency (EAU 2015 Mar). Medical expulsion therapy with alpha-blockers or nifedipine is currently recommended to help expedite stone passage based on previous meta-analyses of randomized trials (EAU 2015 Mar). However, large, high quality randomized trials evaluating medical expulsion therapy are lacking. To address this issue, a recent randomized trial compared tamsulosin 400 mcg vs. nifedipine 30 mg vs. placebo daily for up to 4 weeks as part of expectant management in 1,167 adults aged 18-65 years with ureteric colic. All patients had computed tomography-confirmed single ureteric stone < 10 mm (75% of patients had stones ≤ 5 mm) in diameter. Patients requiring immediate medical intervention, with sepsis or estimated glomerular filtration rate < 30 mL/min, and already taking or unable to take alpha blocker or calcium channel stabilizer were excluded from the trial.

The primary outcome of this trial was spontaneous stone passage within 4 weeks, defined as no need for additional interventions to assist stone passage within 4 weeks of randomization. Additional imaging was done only if clinically indicated and not routinely to confirm stone passage, as this was felt to better reflect actual clinical practice. While 97% of patients were included in the primary outcome analysis, only 62% of patients completed the 4-week questionnaire and were included in the pain management secondary analysis. At 4 weeks post-randomization, rates of spontaneous stone passage were 81% with tamsulosin vs. 80% with nifedipine vs. 80% with placebo, showing no significant differences among the three groups. Prespecified subgroup analyses examined the effectiveness of each medical expulsive therapy vs. placebo by sex, stone size, and stone location, the results of which were all consistent with the overall analysis. There were also no significant differences in pain scores at 4 weeks or analgesic use in patients completing the 4-week questionnaire.

Though previous meta-analyses found alpha-blockers and calcium channel blockers may increase the clearance of ureteral stones, these analyses were limited by high levels of heterogeneity in the methodologies of the included trials. Many included trials were limited by small trial size, lack of blinding, or unclear randomization, negatively affecting the strength of the meta-analysis. On the other hand, this large randomized trial was well powered to detect differences in stone clearance between medical expulsive therapies and placebo, but found no differences with either tamsulosin or nifedipine. It should be noted, however, that these results are inconsistent with a previous large randomized trial comparing tamsulosin vs. nifedipine in adults with 4-7 mm ureteric stones which found that tamsulosin was associated with significantly higher rates of stone expulsion compared to nifedipine (BJU Int 2011 Jul;108(2):276). This prior trial did not include a placebo comparison, however, making it hard to directly compare the results. One potential limitation of the current trial is the definition of the primary outcome as a lack of further intervention rather than confirmed stone clearance. In fact, a small number of patients were reported to require intervention between 4 and 12 weeks. However, the percentage of patients requiring later intervention was very small and equally distributed among the three groups. The secondary pain management outcomes of this trial were also limited by low participation in the 4-week questionnaire. Overall, the results of this trial suggest that the addition of tamsulosin or nifedipine to expectant management does not increase stone clearance in patients with a ureteric stone and should not be recommended for treatment of ureteric colic.

For more information, see the Nephrolithiasis topic in DynaMed.