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Q In patients with urolithiasis, are calcium channel blockers or α blockers more effective than standard therapy for helping patients pass urinary stones?
Clinical impact ratings GP/FP/Primary care ★★★★★★☆ Internal medicine ★★★★★★☆ Emergency care ★★★★★★☆ Surgery—urology ★★★★★☆☆
Medline, PREMEDLINE, CINAHL, EMBASE/Excerpta Medica, abstracts from annual meetings, study authors, and drug manufacturers.
Study selection and assessment:
randomised controlled trials (RCTs) that evaluated calcium channel blockers or α blockers as the main treatment for ureteral stone disease (mean size 3.9–7.8 mm) and had ⩾1 week follow up (range 15–48 d). Studies were excluded if medical therapy was an adjunct to surgery. 9 RCTs (n = 693, mean age range 34–47 y, 25% to 60% women) met the selection criteria. In 3 RCTs, corticosteroids were given to the treatment groups with the calcium channel blocker nifedipine. Non-steroidal anti-inflammatory drugs were given to both treatment and control groups in 7 RCTs. RCTs were pooled using a fixed effects model. Quality assessment of the studies included method of randomisation, concealment of allocation, blinding, loss to follow up, and intention to treat analysis.
proportion of patients who passed stones.
More patients in the treatment group than in the control group passed stones (table). 5 additional RCTs did not have a true control comparator (ie, calcium channel blockers or α blockers were compared with a treatment that was potentially active [eg, corticosteroids]); when these RCTs were added to the meta-analysis, the effect for medical therapy with calcium channel blockers or α blockers remained (relative benefit increase 52%, 95% CI 39 to 65). Mean time to passage ranged from 6 days in several treatment groups to 20 days in 1 control group.
In patients with urolithiasis, medical therapy with calcium channel blockers or α blockers may increase the chance of passing ureteral stones.
Ureteral colic is an extremely painful and costly medical condition. Despite this, surprisingly few RCTs have examined non-invasive methods to speed stone passage. Traditionally, increased fluids (orally or intravenously) and pain control have been the mainstay of treatment. However, the benefits of increased fluids are uncertain.1 While urological intervention is nearly always effective, the associated discomfort, risks, and costs preclude this treatment as routine first line therapy.
The meta-analysis by Hollingsworth et al highlights 2 inexpensive and widely available medications that increased the likelihood of stone passage. However, several issues should be considered. Firstly, in the setting of uncontrollable pain or infection, emergent urological intervention should not be delayed. Secondly, the long term effect on renal function of prolonged partial or complete ureteral obstruction needs clarification. It is not only the proportion of stones that eventually pass but also the time to passage that matters. Thirdly, the role of the other therapies used with the study drugs is uncertain. For several studies, ⩾1 intervention was used, thus making it difficult to separate the independent effects of the drugs of interest. Fourthly, the costs associated with delaying the urological intervention need to be determined. For example, do patients require more analgesics and still have to miss work while waiting for the stone to pass? Fifthly, while the title of the meta-analysis refers to “medical therapy,” it only addresses the role of calcium channel blockers and α blockers. In fact, the only calcium channel blocker studied was nifedipine and the results cannot necessarily be extrapolated to other calcium channel blockers. Finally, the authors conclude that “a high-quality randomized trial is necessary to confirm the efficacy of [these drugs],” implying that the studies included in the meta-analysis were not “high-quality.” I agree that this research question warrants further study because if these drugs are truly effective, they should become part of the standard treatment of ureteral stone disease. Based on the available evidence, it seems reasonable to try nifedipine or an α blocker to facilitate ureteral stone passage while waiting for definitive studies.
For correspondence: Dr B K Hollenbeck, Ann Arbor Veterans Affairs Health Services Research and Development Center of Excellence, Ann Arbor, MI, USA.
Sources of funding: National Institutes of Health and Blue Cross Blue Shield of Michigan Foundation