Alpha-blockers as medical expulsive therapy for ureteral stones

Abstract

Urinary stone disease is one of the most common reasons for patients visiting a urology practice, affecting about 5% to 10% of the population. Annual costs for stone disease have rapidly increased over the years and most patients with ureteral colic or other symptoms seek medical care. Stone size and location are important predictors of stone passage. In most cases medical expulsive therapy is an appropriate treatment modality and most studies have been performed with alpha-blockers. Alpha-blockers tend to decrease intra-ureteral pressure and increase fluid passage which might increase stone passage. Faster stone expulsion will decrease the rate of complications, the need for invasive interventions and eventually decrease healthcare costs. A study on the effect of alpha-blockers as medical expulsive therapy in ureteral stones is therefore warranted. This review aimed to answer the following question: does medical treatment with alpha-blockers compared to other pharmacotherapy or placebo impact on stone clearance rate, in adult patients presenting with symptoms of ureteral stones less than 10 mm confirmed by imaging? Other clinically relevant outcomes such as stone expulsion time, hospitalisation, pain scores, analgesic use and adverse effects have also been explored. We searched the Cochrane Renal Group's Specialised Register to 9 July 2012 through contact with the Trials Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE, handsearching conference proceedings, and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials (RCTs), comparing alpha-blockers with other pharmacotherapy or placebo on ureteral stone passage in adult patients were included. Two authors independently assessed study quality and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Reporting bias was investigated using funnel plots. Subgroup analysis was used to explore possible sources of heterogeneity. Sensitivity analysis was performed removing studies of poor methodological quality. Thirty-two studies (5864 participants) were included. The stone-free rates were significantly higher in the alpha-blocker group (RR 1.48, 95% CI 1.33 to 1.64) when compared to standard therapy. Stone expulsion time was 2.91 days shorter with the use of alpha-blockers (MD -2.91, 95% CI -4.00 to -1.81). Use of alpha-blockers reduced the number of pain episodes (MD -0.48, 95% CI -0.94 to -0.01), the need for analgesic medication (diclofenac) (MD -38.17 mg, 95% CI -74.93 to -1.41) and hospitalisation (RR 0.35, 95% CI 0.13 to 0.97). Patients using alpha-blockers were more likely to experience adverse effects when compared to standard therapy (RR 2.74, 95% CI 1.38 to 5.45) or placebo (RR 2.73, 95% CI 1.50 to 4.96). Most adverse effects were mild of origin and did not lead to cessation of therapy, and several studies reported no adverse events in either the treatment or control group.In 7/32 studies patients and doctors were both blinded. In the other studies blinding was not described in the methods or no blinding had taken place. Two studies described incomplete data and only one study showed a relatively high number of patients who withdrew from the study. These factors limited the methodological strength of the evidence found. The use of alpha-blockers in patients with ureteral stones results in a higher stone-free rate and a shorter time to stone expulsion. Alpha-blockers should therefore be offered as part of medical expulsive therapy as one of the primary treatment modalities.