1. The use of medical therapy to
facilitate passage of kidney
stones
2. Introduction
• Incidence of kidney stones in general
population is increasing
• Number of outpatient and ED visits have
doubled from 1994-2000
• Nearly $2.1 billion dollars in health care
expenditures
3. Introduction
• Traditional therapy includes hydration,
pain relief (NSAIDs), and watchful waiting
for passage of ureteral stone
• Most individuals have small stones
(<5mm), located in distal ureter that can
pass spontaneously
• Urologic intervention is recommended for
ureteral stones persisting >2 months
4. The use of α-antagonist and
calcium channel blockers
• The autonomic nervous system increases
intracellular calcium, which triggers
contraction of ureteral smooth muscle
• Using α-antagonists or CCBs may improve
rates of spontaneous stone expulsion and
decrease transit time by inhibiting ureteral
muscle contraction and allowing for stone
passage
5. Goals of meta-analysis
• Primary Outcome: percent of patients who
passed stones with addition of α-
antagonist or CCB compared to those
patients not receiving this additional
therapy
• Secondary Outcome: time to stone
expulsion
6. Methods
• Inclusion criteria:
– randomized or controlled clinical trials
– >18 years old
– clinical and radiographic diagnosis of acute ureteral
colic
– therapy begun in inpatient or outpatient setting,
including the ED, or on referral to Urology
– use of α-antagonist or CCB compared to a control
group
– studies included the primary outcome measure
7. Methods
• Quality of studies assessed using Jadad scale,
giving each study a score of 0-5 (higher scores
indicate better study quality)
• 2 of the authors selected trials and gathered
data
• Heterogeneity expected:
– the use of different drugs with the same MOA
– combining studies that used additional therapies
(anticholinergics, steroids, and antibiotics)
• Sub-group analyses conducted to evaluate
differences by treatment drug, additional
therapies, an by study quality
8. Results
• 22 RCTs included in meta-analysis
– 13 using α-antagonists
– 6 using CCBs
– 3 using both α-antagonist and CCBs
• Jadad scores ranged from 0-3 in both α-
antagonist and CCB trials
– Only 1 trial was blinded
9. Results
• Tamsulosin used in 13 of 16 trials
• Nifedipine used in all 9 trials
• All trials allowed for pain control (NSAIDs) and
encouraged hydration
• Median follow-up was 4 weeks from time of
enrollment
• Many trials included additional medications
(steroids, antibiotics, GI protective agents,
anticholinergics, anxiolytics, antiemetics) which
were not always matched in treatment and
control groups
10. Results: α-antagonists
• 1235 patients from 16 trials
– stone size range 3-18mm
– all located in distal portion of ureter
– Mean stone size ranged from 4 to 8 mm
• Combined results suggest a benefit in
stone expulsion when combined with
standard therapy
– RR 1.59; 95% CI 1.44 to 1.75
– NNT 3.3; 95% CI 2.1 to 4.5
12. Results: α-antagonists
• 9 trials evaluated time to stone expulsion
– 2-6 day average improvement observed in α-
antagonist group compared to control
– mean time in treatment group <14 days
• Adverse effects were not consistently reported
– overall rate of 4% (dizziness, HA, N/V, asthenia);
transient hypotension occurred in 8 patients (not
requiring discontinuation)
– one patient experienced severe asthenia and dropped
out of study
– no reports of impotence, ejaculatory failure, or
decreased libido
13. Results: CCBs
• 686 patients from 9 trials
– mean stone size 4 to 7 mm in all but 1 study
– all evaluated stones in the distal ureter, but 3
also included the upper and middle ureter
• Combined results suggest a benefit in
stone expulsion when combined with
standard therapy
– RR 1.50; 95% CI 1.34 to 1.68
– NNT 3.9; 95% CI 3.2 to 4.6
15. Results: CCBs
• All 9 trials evaluated time to stone expulsion
– reduction of time seen in 7 trials
– mean time in treatment group <28 days
• Adverse effects not consistently reported
– overall rate of 15.2% (N/V, asthenia, dyspepsia, HA,
drowsiness, euphoria); transient hypotension
occurred in 3 patients (not requiring discontinuation
– 10 patients discontinued therapy (4 with hypotension
or palpitations; 6 with erythema or edema)
– mean decrease in SBP 15mmHg, DBP 8mmHg, HR
8bpm
16. Results
• Sequential exclusion of each study from
the analysis of the α-antagonist and CCB
trials resulted in only minor changes in the
pooled RR for each group
17. Results
• Subgroup analysis found no difference by
study quality
– analyzed 386 patients in 5 α-antagonist trials
with a Jadad score of 3
• Results: RR 1.66 (95% CI 1.45 to 1.89)
– analyzed 380 patients in 4 CCB trials with
Jadad score 3
• Results: RR 1.60 (95% CI 1.28 to 2.01)
18. Results: Subgroup Analysis
• Results did not differ by presence or
absence of other medications
(anticholinergic agents, low-dose steroids,
antibiotics)
• Results did not differ when tamsulosin was
compared to other α-antagonists
19. Limitations
• Heterogeneity of α-antagonist studies
• Overall poor quality of individual studies
• Did not report on number lost to follow-up for
each study
• Search results limited by publication bias
(overestimation of treatment effect)
• Pain was not evaluated as outcome measure
• Did not report or examine dosages of agents
20. Discussion
• Results of this meta-analysis suggest a
significant benefit in stone expulsion rate
when α-antagonist or CCB is added to
standard therapy in medical management
of moderately sized (4 to 8 mm) distal
ureteral stones
21. Discussion
• It is important to find medical means that
promote expulsion rate and shorten time before
passage
– Complications during watchful waiting include:
• repeated renal colic
• urinary infection
• hydronephrosis
– Although endoscopic treatment with ureteroscopy or
extracorporeal shockwave lithotripsy improve stone
passage rates, they require referral to Urology and
are expensive
22. Discussion
• Further research
– medical expulsive therapy for larger stones
– role of steroids
• proposed benefit from preventing edema around the stone
and thus facilitating passagerole of prophylactic antibiotics
• proposed benefit from preventing UTI, which may slow
passage of stone
– role of other α-antagonists
• Tamsulosin 0.4mg daily for 1 month was most common in
these studies; however, Terazosin 5-10mg daily and
Doxazosin 4mg daily appeared to be equally effective
23. Discussion
• Further Research, cont.
– evaluating combinations of α-antagonists and
CCBs to facilitate stone passage
– determining the most appropriate time course
of therapy
• this meta-analysis suggests 2-4 wk time course
24. Conclusion
• Should you use medical management in
patients you see with ureteral stones?
– moderate size, distal ureteral stones
– use in addition to traditional therapies
including pain control (NSAIDs) and hydration
(>2 liters/day)
– α-antagonists seem to have fewer side effects
and are better tolerated by patients than
CCBs
25. References
• Singh, et al. A Systematic Review of
Medical Therapy to Facilitate Passage
of Ureteral Caliculi. Annals of
Emergency Medicine, Volume 50,
Issue 5, Pages 552-563
