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Dr A Singh, Highland General Hospital, Oakland, CA, USA;
Do α-antagonists and calcium channel blockers (CCBs) increase spontaneous passage of kidney stones in adults?
Selected studies compared medical expulsive therapy, using an α-antagonist or CCB, with standard therapy in patients >18 years of age who were clinically and radiographically diagnosed with acute ureteral colic and started treatment in an inpatient or outpatient setting, or on referral to a urologist.
Outcome was proportion of patients who passed kidney stones (stone expulsion rate).
Medline, EMBASE/Excerpta Medica, and Cochrane Controlled Trials Register (1980 to Jan 2007); urological journals (2000 to Jan 2007) and their associated websites; abstracts of major urological conferences (2000–7); and reference lists of relevant articles were searched for randomised controlled trials (RCTs) or controlled clinical trials. 22 RCTs (n = 1921), including 5 published as abstracts, met the selection criteria. 13 used an α-antagonist, 6 used a CCB, and 3 used both. Tamsulosin was the α-antagonist used in 13 studies, and nifedipine was the CCB used in all 9 studies. In 15 studies, mean stone diameter was >5 mm in all treatment groups, and median follow-up across all studies was 4 weeks. All studies evaluated stones in the distal ureter; 3 studies also included stones within the upper and middle ureter. Study quality was poor (median Jadad scale score 2): only 1 trial reported blinding, 6 reported use of an appropriate randomisation process, and 17 reported patient follow-up.
Meta-analyses showed that addition of an α-antagonist or CCB to standard therapy increased spontaneous expulsion of kidney stones (table). Results of prespecified subgroup analyses of trials with potentially confounding medications (ie, anticholinergic agents, low-dose steroids, or antibiotics) or those using an α-antagonist other than tamsulosin were consistent with the main analysis. Adverse effects were not consistently reported in the trials.
Addition of an α-antagonist or calcium channel blocker to standard therapy increases spontaneous expulsion of kidney stones.
Singh A, Alter HJ, Littlepage A. A systematic review of medical therapy to facilitate passage of ureteral calculi. Ann Emerg Med 2007;50:552–63.
Clinical impact ratings: Emergency medicine 6/7; Nephrology 6/7; Surgery/Urology 5/7
Healthcare reform prioritises efficacy, with decreased costs and complications. Kidney stones occur in 13% of men and 7% of women in the USA, with annual expenditures at $2.1 billion in 2000. Thus they lend themselves to therapeutic reforms.1 Since outpatient and physician visits for Medicare beneficiaries with kidney stones in the USA have also increased, the ceiling for expenditures will rise.1 Standard therapies, such as extracorporeal shock wave lithotripsy, are expensive and associated with serious complications.2 Therefore, efforts to expel ureteral stones with either α-antagonists or CCBs hold promise.3
The systematic review by Singh et al evaluated available evidence for medical expulsive therapy to facilitate passage of ureteral calculi. Pooled analysis of 22 studies showed that these agents facilitated passage of stones, most >5 mm (relative risk 1.59 for α-antagonists; 1.50 for CCBs), with adverse effects of 4% and 15%, respectively.
As noted by Singh et al, one-third of meta-analyses are invalidated later as a result of larger RCTs, and despite the comprehensiveness of their meta-analysis, the review still has limitations. A median Jadad score of 2 for trials included in the analysis suggests that studies to date are not of robust quality and often are not blinded. In addition, studies of α-antagonists showed evidence of publication bias (by Egger’s test and Begg’s test).
This meta-analysis is definitely encouraging, if not definitive, evidence for medical expulsive therapy. Such encouragement, especially since medical treatment is consistent with goals of healthcare reform, should result in a large, well-designed RCT soon.
Source of funding: no external funding.