HARRY WINKLER Director, section of Endourology Kidney stone center - Dept.of Urology - Med

Alpha blockers have no
   role in renal colic

        HARRY WINKLER
 Director, section of Endourology
       Kidney stone center
           Dept.of Urology
        ‘Sheba’ Medical Center

Financial and Other Disclosures
   Off-label use of drugs, devices, or other agents: None
   including our local regulatory agency
   Data from IRB-approved human research is not presented

    I have the following financial interests or
                                                            Disclosure code
            relationships to disclose:
No financial relationships                                        N

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 Tamsulosin, which is a selective α1A/α1D-adrenergic
  receptor antagonist, has been widely studied in the
  context of MET for patients with distal ureteric
  stones smaller than 10 mm.

 It has been proved that tamsulosin increases stone
  expulsion rates, decreases pain, reduces mean time to
  stone expulsion and decreases analgesic usage when
  compared with placebo

                              Can J Urol 2010; 17:5178–83
                              Urology 2010;75: 4–7

MEDICAL EXPULSIVE THERAPY ( met ) HAS
BECOME AN ESTABLISHED METHOD OF TREATMENT.

Thirty-two studies (5864 participants).

 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).

2014 Cochrane - Study limitations

 Included many heterogeneous trials

 Most studies have a relatively small number of patients,
  performed in a single-centre, with variable methodological
  quality.

 In ONLY 7/32 studies patients and doctors were both
  blinded.

 Two studies described incomplete data

 Proximal and mid-ureteral stones were assessed in only
  three studies ( 3/32 )

 A large-scale, placebo-controlled (multicenter RCT may be
  needed to draw final conclusions concerning the role of
  alpha-blockers in all ureteral stones.

24 centers in the UK   Lancet 2015; 386: 341–49
1167 participants

Medical Expulsive Therapy for Ureteral Stones:
                No Better Than Placebo
       bruce soloway, reviewing Pickard R et al. Lancet 2015 May 18

 Researchers in the U.K. enrolled 1136 symptomatic adults,
  each with a single ureteral stone

Comment :( LANCET)

This trial, designed to reflect current recommendations
and clinical practice

 Definitively demonstrates the ineffectiveness of
  medical expulsive therapy for ureteral stones

 Reaffirms the essential importance of large, well-
  designed, randomized trials for assessing clinical
  interventions and formulating treatment guidelines

                            Bruce Soloway, NEJM journal watch

“…This may change future
  guidance on MET”…

Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for
Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized,
Double-blind, Placebo-controlled Trial
Zhangqun Ye et al. Eur Urol 73 ( 2018 ) 385– 391

The primary end point was the stone expulsion rate, defined as stone
expulsion, confirmed by negative findings on CT, over the 28-d

tamsulosin significantly facilitates the passage of distal ureteral
stones and relieves renal colic.

Tamsulosin provides a superior expulsion rate for stones >5 mm,
but does not show any difference from placebo for stones ≤5 mm.

Contemporary Management of Stone Disease:
            The New EAU Urolithiasis Guidelines

            Matthew Bultitude et al. EUR UROL, 6 9 ( 2 0 1 6 ) 4 8 3 – 4 8

A randomised multicentre placebo-controlled trial of 1167 pts.

“this is a single trial, it had more patients
than the meta analysis data, and significant
weight needs to be given to this paper when
deciding whether to continue to offer MET
for ureteric stones”.
                                             Pickard R, et al. Lancet 2015;386:341–9

Effect of Tamsulosin on Passage of Symptomatic Ureteral Stones :
A Randomized Clinical Trial
Andrew C. Meltzer , JAMA Internal Medicine , June 18, 2018.

a multicenter, randomized,
double-blind, placebo
controlled clinical trial
among emergency
department patients

The Study of Tamsulosin
for Urolithiasis in the
Emergency Department
(STONE)

Phase 1 : 2008 to 2009 ------109 pts. single site
Phase 2 : 2013 to 2016 at 6 emergency department---------403 pts.
Total – 512 pts.

Symptomatic ureteral stones determined by NCCT
Size < 9 mm in diameter

Follow-up CT scan after the 28-day treatment period

The primary outcome : passage of stone within 28 days after
randomization, as determined by the participant’s visualization or
physical capture of the stone

Use of medical expulsive therapy in ED - 15% to 55%.
Ganesan V,   J Urol. .196:1467-1470;2016

 Our findings agree with those of 2 recent large multi site clinical
  trials conducted in the United kingdom
   Pickard R, Lancet. 2015;386(9991):341-349.(SUSPEND)

 theAustralian study, 403 patientswith distal ureteral stones 10 mm
  or less in diameter were enrolled in 5 emergency departments and
  randomized to either tamsulosin or placebo.
 Furyk JS, Ann Emerg Med. 2016;67(1):86-95.e2.

No difference was detected between treatment groups in the overall
rate of urinary stone passage after 28 days of therapy.

Strengths of the study

 Recruited from emergency departments
 Overall , diverse sample with respect to race , making
  results more generalizable.
 A high rate of ascertainment of the primary outcome,
  having contacted 97.1% of study participants
 A high rate of adherence to the study medication
 A broad range of secondary outcomes
 Follow-up CT scan in most of our phase 2
 Included all patients who had stones in any part of the
  ureter to increase the generalizability of our study.

Conclusions

 Stone passage rates were 50% in the tamsulosin group and 47% in
  the placebo group (relative risk, 1.05; 95.8% CI, 0.87-1.27; P = .60)

 Our findings do not support the use of tamsulosin for symptomatic
  urinary stones smaller than 9 mm

 Although tamsulosin may still play a role in medical expulsive
  therapy for larger stones, guidelines that recommend tamsulosin for
  ureteral stones may need to be revised

The new 2016 EAU guidelines on MET

The EAU Recommendations in 2016 have been
downgraded to grade C

A potential benefit of MET (a-blockers) is most likely for
distal ureteral stones >5 mm

The question is whether to base treatment decisions on meta-
analyses composed of single-center, small, mainly low-quality trials
favoring MET or on a few large high quality trials with findings of
no significant effect.

Medical Expulsive Therapy for Distal Ureteral Stones:
                           The Verdict is In
Philipp Dahm et al. EUR UROL 73 ( 2018 ) 39 2– 39 3

 Treatment is effective in patients with larger stones in the lower
  ureter
 No further trials are required

 In many countries, CT imaging of patients is not the norm.

 The trade-off for MET may be less clear cut

 Most stones presenting at the distal ureter are small in size

 Remains unclear is the effectiveness of MET for stones in the
  proximal and mid ureter

It is important to inform patients about the possible but
as yet unproven benefit using a-blockers as well as their
off-label use and possible side effects !!

               THANK YOU !