Do alpha blockers safely speed passage of subcentimeter ureteral stones?
Compared with patients receiving standard therapy (e.g., fluids, analgesics), placebo, or calcium channel blockers, patients receiving alpha blockers had about three fewer days to ureteral stone expulsion and were less likely to be hospitalized. Adverse effects of alpha blocker therapy are generally tolerable. (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)
The prevalence of kidney stone disease has increased in recent years and affects 5% to 10% of the population.1 Alpha blockers relax smooth muscle and decrease intraureteral pressures. The authors of this Cochrane meta-analysis evaluated the role of alpha blockers as a medical therapy to speed the passage of ureteral stones.
The authors identified 32 randomized controlled trials (RCTs) and quasi-RCTs with 5,864 participants. Participants were symptomatic adults with radiologically confirmed ureteral stones 10 mm or smaller. Exclusion criteria included urinary tract infection, hydronephrosis, or other underlying abnormalities of the kidney or ureters.
Alpha blockers used included tamsulosin (Flomax; 0.2 or 0.4 mg), alfuzosin (Uroxatral; 10 mg), doxazosin (Cardura; 4 mg), and terazosin (Hytrin; 2 or 5 mg); most studies used tamsulosin in a dosage of 0.4 mg once daily. The majority of studies ran two to four weeks and compared alpha-blocker therapy plus standard therapy (hydration, pain killers, nonsteroidal anti-inflammatory drugs, corticosteroids, prophylactic antibiotics) with standard therapy plus placebo. Others compared alpha blockers with calcium channel blockers such as nifedipine (Procardia; 30 mg) or the antimuscarinic tolterodine (Detrol; 4 mg).
The overall stone expulsion time was three days shorter with alpha blockers than with standard therapy, with a mean expulsion time of seven rather than 10 days. When looking at stone-free status by the end of the study, patients taking alpha blockers had much improved clearance compared with those in standard therapy (30 studies with 2,378 participants; relative risk [RR] = 1.48; number needed to treat [NNT] = 4), and also when compared head-to-head with patients taking calcium channel blockers (four studies with 3,486 participants; RR = 1.19; NNT = 4.8). A Chinese RCT of 3,189 patients accounted for most of the latter findings; the study was appropriately masked and considered at low risk of bias.2
The benefits of alpha blockers were robust, irrespective of whether the stone was smaller than 5 mm or was 5 to 10 mm in diameter. Alpha blockers greatly reduced the need to hospitalize (four studies with 313 participants; RR = 0.35; NNT = 4.2) and, to a more modest degree, reduced the number of pain episodes and amount of pain medication used.
Only five studies reported adverse effects. In these studies, about 10% of participants (88 out of 845) experienced dizziness, palpitations, headache, rhinitis, retrograde ejaculation, fatigue and weakness, cutaneous reaction, or postural hypotension. Most adverse effects were mild and did not lead to cessation of therapy.
Specialty guidelines published in 2007 recommend use of alpha blockers to help pass subcentimeter ureteral stones in otherwise stable patients.3 Duration of treatment is not specified by the guidelines, but this Cochrane review suggests that passage should occur within one month, if not two weeks. Family physicians should consider alpha blockers as first-line therapy for patients with otherwise uncomplicated subcentimeter ureteral stones.