Primary Care Corner with Geoffrey Modest MD: alpha blockers help with ureteral stone passage

By Dr. Geoffrey Modest

A recent meta-analysis/systematic review confirmed that a-blockers are efficacious in the treatment of patients with ureteral stones (see doi.org/10.1136/bmj.i6112 ).

Details:

• 55 unique RCTs, with 5990 randomized patients, mostly in European and Asian subjects. Mean stone size 5.7 mm, tamsulosin was the a-blocker in 40 studies, mean follow-up of 28 days
• Primary outcome: proportion of patients who passed their stone
• Secondary outcomes: time to passage of stone, number of pain episodes, and proportion of patients who had surgery/were admitted to hospital/experienced adverse events

Results:

• a-blockers facilitated the passage of stone, with risk ratio (RR)=1.49 (1.39-1.61), a 49% higher likelihood of stone passage (moderate qualityevidence)
  • The pooled risk difference was 0.27, meaning that 4 patients needed treatment for 1 to get benefit
  • The pooled % for stone passage was 75.8% in the a-blocker group vs 48.4% in the control group. this was basically independent of the type of a-blocker used or if imaging was done to assess stone passage
• Subgroup analysis
  • No benefit for those with small stones, RR=1.19 (1.00-1.48), though on the cusp of being significant
    • Review of their figure of stone size:
      • Small trend to benefit if <5mm, increasing trend if <6mm
      • Reasonably clear benefit if >6mm, and esp if >8mm
    • In those with larger stones, RR=1.57 (1.39-1.61), a 57% higher likelihood of stone passage
    • No difference based on where the stone was located (upper or middle ureteral stones)
  • Secondary analyses, benefit of a-blocker:
    • Shorter time to stone passage, mean decrease of 3.79 days (3.14 to 4.45 days), moderate quality evidence
    • Fewer episodes of pain, mean decrease of 0.74 (0.21 to 1.28), low quality evidence
    • Lower risk of surgical intervention, RR 0.44 (0.37-0.52), moderate quality evidence
    • Lower risk of hospital admission, RR 0.37 (0.22-0.64), moderate quality evidence
    • Similar risk of adverse events, low quality evidence

Commentary:

• This meta-analysis/systematic review follows on the tail of a recent RCT (see Pickard R. Lancet 2015; 386: 341), finding that neither tamsulsin4 mg nor nifedipine 30mg decreased the need for further intervention for stone clearance within 4 weeks of randomization. I am often concerned that we all tend to give disproportionate weight to the newest study. In fact this Pickard study, though a large one with 1136 patients, had 75% of them with stone size <5mm (which pass pretty easily on their own, and the above meta-analysis did not find much benefit to the a-blocker), and though the remaining 25% were >5mm, they do not indicate whether this was mostly 5.5mm or 9.8mm. And, likely because of the small size of the stones overall, 80% of the patients did not need any further urologic intervention in the ensuing month in either the intervention or control groups.
• I should also reiterate the caveat that meta-analyses and systematic reviews are not the be-all and end-all, but are fraught with their own limitations, and are not considered very high on the evidence-based medicine hierarchy (and not even included in the pyramid of the most thoughtful pyramids, to my thinking. See https://stg-blogs.bmj.com/bmjebmspotlight/2016/11/21/primary-care-with-geoffrey-modest-md-lessons-ive-learned-from-looking-at-the-medical-literature/ )

So, bottom line is that this review does support the use of a-blockers in those with ureteral stones, especially if >5-6mm in size. There are also studies showing that calcium-channel blockers help (most studied being nifedipine), and the data are mixed as to whether the a-blockers or calcium channel blockers are better.