John C. Conway, and Benjamin W. Friedman, MD
Urinary tract stones are common and usually pain- ful. Lifetime prevalence is approximately 10%.1 Direct health care costs are estimated to be over $10 billion dollars annually.2 First-line treatment is typically analgesia with nonsteroidal anti-inflammatory drugs until the stone passes. If the stone does not pass spontaneously, urologic intervention may be necessary.3 Spontaneous passage rates for small stones less than 5 mm is 68% and for stones between 5 and 10 mm is 47%.4 Certain medications such as alpha blockers are sometimes used to hasten passage of stones and decrease the need for urologic intervention or hospitalization. Alpha blockers act on ureteral alpha-1 receptors and decrease the basal tone and peristalsis, thereby facilitating stone passage.5 However, conflicting results from randomized controlled trials (RCTs) have limited their use. The systematic review discussed here is an update of a 2014 Cochrane review.6 It includes several new, large, RCTs.
The purpose of this systematic review was to determine the effectiveness of alpha blockers for adult patients with symptomatic ureteral stones measuring less than 1 cm and confirmed by imaging. The systematic review included 67 trials with 10,509 patients. The included studies compared alpha blockers with placebo or medical therapy with nonsteroidal anti-inflammatory drugs, corticosteroids, or antispasmodics. The primary outcomes were stone clearance (defined as stone free imaging, symptomatic relief, or stone collection by the last day of the trial) and major adverse events (defined as orthostatic hypotension, collapse, syncope, palpitations, or tachycardia). Secondary outcomes included hospitalization and the need for surgical intervention. Subgroup analysis compared stone clearance rates for stones 5 mm or smaller versus stones greater than 5 mm. Further analyses examined only high-quality studies, excluding studies at high risk of bias.6Overall, the use of alpha blockers was associated with increased stone passage (relative risk [RR] = 1.45, 95% confidence interval [CI] = 1.36 to 1.55, absolute risk difference [ARD] = 28%, number needed to treat [NNT] = 4, low-quality evidence) without increasing the risk of major adverse events. Alpha blockers were also associated with a lower risk of hospitalization (RR = 0.51, 95% CI = 0.34 to 0.77, ARD = 14%, NNT = 7, moderate-quality evidence) and no difference in the risk of surgical intervention (low-quality evidence). The subgroup analysis based on the size of the stone revealed that alpha blockers did not impact passing of stones ≤ 5 mm but did improve passing of stones > 5 mm (RR = 1.45, 95% CI = 1.22 to 1.72, ARD = 30%, NNT = 3, moderate-quality evidence).6 When the analysis was performed using high-quality trials only, alpha blockers increased stone passing (RR = 1.09, 95% CI = 1.06 to 1.13; ARD = 7%, NNT = 15, high-quality evidence, five studies, 4,133 participants) while having no effect on major adverse events, hospitalization, or surgical intervention.6
This review is limited in several ways. Most importantly, the quality of evidence for most outcomes was low due to several methodologic limitations of the included studies, inconsistency in study results, publication bias, a lack of prospectively stratified subgroups, and clinically important heterogeneity.
The findings of this meta-analysis are consistent with other recently published meta-analyses.7 However, some included RCTs, such as the SUSPEND trial, did not demonstrate a benefit for MET.8–10 The findings of individual RCTs may have been skewed toward no benefit because of limited sample size, a high percentage of smaller stones, and insufficient power to detect group differences between small and large stones. Additionally, a recent, large RCT, the STONE trial, was not included in this meta-analysis. The STONE trial, which included 512 patients found no significant differences in outcomes.11 These findings are unsurprising as this trial has the same limitations as other individual RCTs. Because of the lack support for MET by several well-designed RCTs, it is important to counsel patients on the potential limitations of the evidence that is being used to recommend MET.
In summary, using alpha blockers appears to be beneficial in increasing ureteral stone passage (especially if stones are >5 mm) and reducing hospitalization. They appear to be safe as they do not increase the risk of major adverse events when compared to placebo, nonsteroidal anti-inflammatory drugs, corticosteroids, or antispasmodics. Because benefit is likely (particularly for stones larger than 5 mm) and there is no apparent harm, we have assigned a color recommendation of green (benefits > harm) to this treatment.
- Ramello A, Vitale C, Marangella M. Epidemiology of nephrolithiasis. J Nephrol 2000;13:S45–50.
- Litwin MS,Saigal CS, editors. Table 14.47. Economic impact of urological disease. In: Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2012; NIH Publication No. 12-7865; pp. 486.
- Assimos D, Krambeck A, Miller NL, et al. Surgical management of stones: American Urological Association/ Endourological Society guideline PART I. J Urol 2016;196:1153–60.
- Preminger GM, Tiselius HG, Assimos DG, et al. 2007 guideline for the management of ureteral calculi. J Urol 2007;178:2418–34.
- Morita T, Wada I, Saeki H, Tsuchida S, Weiss RM. Ureteral urine transport: changes in bolus volume, peristaltic frequency, intraluminal pressure and volume of flow resulting from autonomic drugs. J Urol 1987;137:132–5.
- Campschroer T, Zhu X, Vernooij RW, Lock TM. a-blockers as medical expulsive therapy for ureteric stones: a Cochrane systematic review. BJU Int 2018;122:932–45.
- Hollingsworth JM, Canales BK, Rogers MA, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ 2016;355:i6112.
- Furyk JS, Chu K, Banks C, et al. Distal ureteric stones and tamsulosin: a double-blind placebo-controlled, randomized, multicenter trial. Ann Emerg Med 2016;67:86–95.
- Pickard R, Starr K, MacLennan G, et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015;386:341–9.
- Sur RL, Shore N, L’Esperance J, et al. Silodosin to facilitate passage of ureteral stones: a multi-institutional, randomized, double-blinded, placebo-controlled trial. Eur Urol 2015;67:959–64.
- Meltzer AC, Burrows PK, Wolfson AB, et al. Effect of tamsulosin on passage of symptomatic ureteral stones. JAMA Intern Med 2018;178:1051–57.