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Three Part Question

In [adult patients with urinary calculi] is [treatment with alpha receptor blockers superior to treatment with calcium channel antagonists] at [increasing the speed and success of spontaneous stone passage]?

Clinical Scenario

A 51 year old presents to A&E with loin pain and macroscopic haematuria and a diagnosis of renal calculi is made. The patient’s pain is adequately controlled and the decision is discharge with Medical Expulsive Therapy (MET) – but you don’t know whether to prescribe alpha-adrenergic antagonists or calcium channel blockers.

Search Strategy

Ovid MEDLINE 1946 to Nov week 2 2012 and Embase 1980 to 2012 Week 46 via OVIDSP interface.
[adrenergic alpha antagonist.mp OR alpha blocker$.mp. OR tamsulosin.mp. OR flomax.mp. OR alfuzosin.mp. OR doxazosin.mp. OR terazosin.mp. OR silodosin.mp. OR calcium antagonist$.mp. calcium channel blocker.mp. OR nifedipine.mp. OR nimodipine.mp. OR amlodipine.mp. OR felodipine.mp.] AND [((renal.mp. OR urinary.mp. OR kidney$.mp. OR urological.mp.) AND (stones.mp or calcul$.mp)) OR urolithiasis.mp. OR nephrolithiasis.mp.] limited to English language and human and “therapy (maximises sensitivity)”

Cochrane Database of Systematic Reviews 2005 to June 2012
(stones OR calculus OR urolithiasis OR nephrolithiasis)

Search Outcome

OVIDSP: 597 studies were found in total: five papers were felt to be relevant to the three-part question.

Cochrane: One relevant review protocol was found, but no relevant completed reviews.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Dellabella et al, 2005, Italy	210 patients with ureteral calculi >4mm visible on ultrasound or plain x-ray. Patients randomised between treatment with 80mg phloroglucinol, 0.4mg tamsulosin and 30mg nifedipine. Each group also received cotrimoxazole for 8 days and 30mg deflazacort for 10 days.	Randomized controlled trial	Stone expulsion as confirmed by x-ray and/or ultrasound and expulsion time.	Stone expulsion in 45/70 patients on phloroglucinol, 68/70 in the tamsulosin group and 54/70 in the nifedipine group. Mean time to expulsion was 120h (IQR 72 – 186h), 72h (IQR 24 -120 h) and 120h (IQR 72-192h) respectively.	No blinding of treatment.
Porpiglia et al, 2004, Italy	86 patients referred to urology in a single centre with stones in the lower ureteric tract <1cm diameter, between September 2002 and September 2003. Stone presence confirmed with ultrasound +/- x-ray. Randomised to receive 30mg nifedipine or .4mg tamsulosin or act as control. Patients in the first two groups also received 30mg deflazacort and misoprostol, patients in the 3rd group only received analgesia. Followed up for 28 days.	Randomised controlled trial.	Stone expulsion	24/30 patients in the nifedipine group vs. 24/28 patients in the tamsulosin group vs. 12/28 in the control group.	No blinding. Additional treatments used in the first two groups but not the control group.
			Mean time to expulsion	9.3 days (3 – 20 days) vs. 7.9 days (1-15 days) vs. 12 days (3 – 20 days) in each group respectively.
Ye et al, 2011, China	3189 patients, aged 18-50y, admitted as an emergency for renal colic at one of 10 centres with a 4-7mm distal ureteric stone visible on x-ray, ultrasound, IVU or CTscan. Patients were randomised to receive 0.4mg tamsulosin once daily or 10mg nifedipine three times daily. Patients were asked to filter their urine.	Randomised trial	Expulsion of stone – all patients had a non-contrast CT scan weekly for up to four weeks. CT scan reported without knowledge of the assigned treatment group.	1530/1596 (95.8%) of patients in the tamsulosin group passed their stone vs. 1171/1593 (73.51%) patients in the nifedipine group. (P < 0.01)	Not blinded. Patients who had stone expulsion prior to taking 1st medication, withdrew consent or were lost to follow up were not analysed.
			Time to passage of stone.	78.35h (26.23 – 145.92) vs. 137.93h (84.41 – 211.24) in each respective group. (P < 0.01)
Zhang et al, 2009, China	314 patients diagnosed with distal ureteral stones on basis of US, x-ray or CT scan at one centre between January 2004 and April 2008. Patients were split according to the stone size into 3 groups and then each group was randomised into 3 treatment groups: 30mg nifedipine daily, 0.4mg tamsulosin daily or EWSL. All patients also received 0.1g levofloxacin bd for the first 7 days and were offered 75mg im diclofenac daily for the trial period.	Randomised controlled trial.	Stone free rate – patients all received plain x-ray and US to check for presence of visible stones on weekly basis. Asymptomatic patients with visible stones <3mm were considered stone free.	66/97 in the nifedipine group, vs. 75/102 in the tamsulosin group vs.91/104 in the ESWL group.	Patients with uncontrollable symptoms excluded from study. No blinding.
Keshvari, 2006, Iran	64 patients referred to one centre with confirmed juxtavesical stone <1cm in diameter. Randomised to tamsulosin .4mg daily, nifedipine 20mg daily or no treatment.	Randomised controlled trial	Stone expulsion rate	18/20 patients in tamsulosin vs. 14/20 in nifedipine group vs. 11/24 in control group.	Only able to obtain abstract so no information about randomisation methods or blinding.
			Average time to expulsion.	16 days, 20 days and 18 days respectively
			Need for transurethral lithotripsy	2/20, 5/20 and 13/24 respectively.

Comment(s)

Medical Expulsion Therapy (MET) is becoming more commonplace as an effective means of managing uncomplicated renal stones. MET is thought to work by causing relaxation of the smooth muscle in the ureter wall. Both calcium antagonists and alpha adrenoceptor blockers appear to have beneficial effects compared with placebo. In all of the selected papers patients taking tamsulosin were more likely to pass a renal calculus and in the cases where expulsion did occur it happened more quickly than for the patients taking nifedipine. This is most noticeable in the study by Ye et al due to the large numbers involved and the very significant effect. Each of the studies excluded a variety of groups of patients with known allergies to the selected agents, diabetes, renal disease, hypertension etc so these factors would have to be taken into account in prescribing these agents. Although these effects are presumably dependent on the pharmacological class of these agents only tamsulosin and nifedipine have been specifically studied in these trials.

Clinical Bottom Line

In patients with renal colic due to uncomplicated ureteric calculi, administration of tamsulosin increases the likelihood of spontaneous expulsion of the stone and decreases the time taken for this to occur compared with nifedipine.

References

1. Dellabella M, Milanese G, Muzzonigro G. Randomized Trial of the efficacy of Tamsulosin, Nifedipine and Phloroglucinol in Medical expulsive Therapy for distal ureteric calculi. J Urol 2005; 174(1):167:72
2. Porpiglia F, Ghignone G, Fiori C et al Nifedipine versus Tamsulosin for the management of lower ureteral stones. J Urol 2004; 172(2):568-71.
3. Ye Z, Yang H, Li H et al. A multicentre, prospective, randomized trial: comparative efficacy of tamsulosin and nifedipine in medical expulsive therapy for distal ureteric stones with renal colic. BJU Int. 2011; 108(2):276-9.
4. Zhang MY, Ding ST, Lü JJ et al. Comparison of tamsulosin with extracorporeal shock wave lithotripsy in treating distal ureteral stones. Chin Med J (Engl) 2009; 122(7):798-801.
5. Keshvari M, Taghavi R. The effect of tamsulosin in facilitating of juxtavesical stones\' passage. Medical Journal of Mashhad University of Medical Sciences 2006:48(90):425–430.