Medical Expulsive Therapy (Alpha Blockers) for Urological Stone Disease
Benefits in NNT
1 in 4 were helped (stones passed)
1 in 7 were helped (fewer hospitalizations)
No one was helped (no surgical intervention was prevented)
28% higher chance of passing the stone
14% decrease in hospitalization
Harms in NNT
No difference in major adverse events
No difference in major adverse events
Source. Campschroer T, Zhu X, Vernooij RWM, Lock TMTW. α-blockers as medical expulsive therapy for ureteric stones: a Cochrane systematic review. BJU Int. 2018;122 932-945.
Study Population: 10,509 adult patients with symptomatic ureteral stones less than 1 cm confirmed by imagining
Efficacy EndpointsPassing the stone, hospitalization, surgical intervention
Harm EndpointsMajor adverse events (orthostatic hypotension, collapse, syncope, palpitations, or tachycardia)
NarrativeUrinary tract stones are common and usually painful. Lifetime prevalence is approximately 10%.1 Direct healthcare costs are estimated to be over $10 billion dollars annually.2 First-line treatment is typically analgesia with non-steroid anti-inflammatory drugs until the stone passes. If the stone does not pass spontaneously, urological intervention may be necessary.3 Spontaneous passage rates for small stones less than 5 mm is 68% and for stones between 5 mm 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, randomized controlled trials.
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 non-steroidal anti-inflammatory drugs, corticosteroids, or anti-spasmodics. 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.6
Overall, 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%; Number-needed-to-treat [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, 4133 participants) while having no effect on major adverse events, hospitalization, or surgical intervention.6
CaveatsThis review is limited in several ways. Most importantly, the quality of evidence for most outcomes was low due to several methodological 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, 9, 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, non-steroidal anti-inflammatory drugs, corticosteroids, or anti-spasmodics. 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.
The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.
AuthorJohn Conway, BS; Benjamin W. Friedman, MD
Supervising Editor: Shahriar Zehtabchi, MD
Published/UpdatedFebruary 3, 2020
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