Background: The number of visits to primary care physicians and emergency departments for a diagnosis of urolithiasis, as well as the associated expenditures, has doubled from 1994 to 2000. Most of the stones implicated are small (less than 5 mm) and do not require surgical intervention. There is some evidence that alpha antagonists and calcium channel blockers can enhance and speed up stone expulsion by inhibiting ureteral spasms. Singh and colleagues conducted a systematic review to evaluate the literature on medical expulsive therapy for stones in the distal ureter.
The Study: The authors searched Medline, EMBASE, and Cochrane databases for randomized or controlled studies on medical treatment of urolithiasis using alpha antagonists or calcium channel blockers. After applying exclusion criteria, 22 of 4,443 articles were included in the analysis. Three studies evaluated alpha antagonists and calcium channel blockers; six studies evaluated only calcium channel blockers; and 13 studies evaluated only alpha antagonists. Tamsulosin (Flomax) was used in 13 of the studies on alpha antagonists; terazosin (Hytrin) and doxazosin (Cardura) were used in the remaining three studies. Nifedipine (Procardia) was used in the nine studies on calcium channel blockers. The median follow-up period was four weeks.
Results: The pooled data from alpha antagonist studies were derived from 16 trials with 1,235 patients who had distal ureteral stones ranging from 3 to 18 mm in diameter. When combined with standard therapy, use of alpha antagonists improved stone expulsion (as defined by comparing expulsion rates in the intervention group versus a control group). The relative risk (RR) was 1.59 (95% confidence interval [CI], 1.44 to 1.75), with a number needed to treat (NNT) of 3.3 (95% CI, 2.1 to 4.5). However, there was some evidence of publication bias. Nine trials that evaluated time to stone expulsion found an improvement of two to six days in patients receiving alpha antagonists compared with a control group. Mild adverse effects were observed. One patient who experienced severe asthenia discontinued therapy.
The pooled data from calcium channel blocker studies were extracted from nine trials with 686 patients who mostly had stone sizes greater than 5 mm. All of the studies evaluated stones in the distal ureter, but three studies also included stones in the upper and middle ureteral tract. When combined with standard therapy, the use of calcium channel blockers improved stone expulsion rates. The RR was 1.50 (95% CI, 1.34 to 1.68); the NNT was 3.9 (95% CI, 3.2 to 4.6). There was no evidence of publication bias. Seven of nine trials that evaluated time to stone expulsion found a reduction in time with calcium channel blockers compared with standard therapy. Mild adverse effects were observed. Ten patients discontinued therapy (four because of hypotension or palpitations and six because of erythema or edema).
Conclusion: In patients with distal ureteral stones, alpha antagonists and calcium channel blockers facilitated stone expulsion rates when combined with standard therapy. Mean time to stone expulsion in patients receiving alpha antagonists was fewer than 14 days; in patients receiving calcium channel blockers it was fewer than 28 days. Adverse effects occurred in 4 percent of patients receiving alpha antagonists and in 15.2 percent of those receiving calcium channel blockers. The authors conclude that, although tamsulosin was the most commonly used alpha antagonist, evidence suggests terazosin and doxazosin would have a similar benefit.