Three Part Question
In [adult patients with chronic anal fissure] is [Diltiazem (DTZ) cream (2%) superior to Glycerinetrinitrate (GTN) cream(0.2%)] in [providing symptomatic relief and healing of anal fissure]
A 30 year old male presents in surgical outpatient with typical history of chronic anal fissure. Clinical examinations confirms this. You decided to try medical treatment as first line in managing his condition however you wonder whether DTZ (2%) or GTN (0.2%) cream would provide better symptomatic relief and promote healing of anal fissure.
Medline 1950 – November 2006 using the Dialog Datastar and OVID interface and EMBASE 1974 – November 2006 using the Dialog Datastar interface.
[GTN OR glycerine trinitrate] AND [Diltiazem OR calcium channel blocker] AND [anal fissure] Limited to English.
A total of 221 papers were found out of which 4 were deemed relevant to our question. We found two RCTs directly related to our question are presented in the table below. We also found two systematic review on medical management of chronic anal fissure, one by R. Nelson who also wrote a Cochrane review on the same topic and the other by R. D Madoff. We excluded these studies from this BET as both the systematic reviews and Cochrane review covered all the medical treatment modalities for chronic anal fissure (including the two RCTs presented in the table below) and the conclusion driven is not specific to our question. We have included two prospective studies relevant to our BET focussing on role of Diltiazem cream in healing GTN cream resistant anal fissures.
|Author, date and country
||Study type (level of evidence)
|47 adult patients with chronic anal fissure that had failed treatment with 0.2% GTN cream||Prospective Study||Efficacy of treatment||At 8 week, 46 patients completed course of DTZ cream, out of these 22 (48%)had healed fissure .||No randomization|
|Side effect of treatment||Perianal itching was noted by all patient.|
|Recurrence||At 44.9 weeks (median duration of follow up) 2 patients had recurrence of symptomatic anal fissure|
|43 adult patients with chronic anal fissure
Group A included 21 patients who received GTN (0.5%) ointment
Group B included 22 patients who received DTZ (2%) ointment||PRCT||Efficacy of treatment||In group A, the anal fissure healed in 18 of 21 (85.7%) patients at 8 weeks, out of these 10 had healed within 2 weeks. In group B healing occurred in 19 of 22 (90%)||The sample size is inadequate to show the difference
Patients not followed for recurrence|
|Side effects of treatment||In group A, 7 out of 21 patients (33.3%) experienced side effects mainly headache whereas no side effects were noted in group B.|
|60 adult patients with chronic anal fissure||PRCT||Efficacy of treatment||At 8 weeks, 25 of the 29 patients in the GTN group deemed to be healed (n = 12) or improved (n = 13), compared with 24 of the 31 patients in the DTZ group deemed to be healed (n = 8) or improved ( n = 16) (RR 0.69 (95 percent c.i. 0.39 to 1.22), P = 0.21).||Note: Improvement here means that the fissure was present but the patients were asymptomatic.
The sample size is inadequate to show the difference|
|Side effect of treatment||After 6-8 weeks of treatment, 21 of 29 patients in the 0.2 percent GTN group experienced side-effects, compared with 13 of 31 in the 2 percent DTZ cream group (RR 1.84 (95 percent c.i. 1.11 to 3.04), P = 0.01)|
|Recurrence||At 12 week, 2 patients has recurrence after healing in the GTN group, whereas none of the patients in the DTZ group had such recurrence.|
|39 adult patients with chronic anal fissure that had failed treatment with 0.2 percent GTN cream||Prospective Study||Efficacy of treatment||At 8 weeks, complete healing of anal fissure was seen in 19 of 39 patients (49%), pain was significantly reduced (P < 0.001)||No randomization|
|Side effect of treatment||3 patients (7.8%) reported itching, one patient (3.9%) developed headache, drowsiness and mood swings|
|Recurrence||At 12 months, no recurrence in patients healed by DTZ cream|
Both RCT have inadequate sample size to show the difference and may me treated as a pilots for a larger size study. Also a long term follow up is required to assess the true recurrence rate.
Note that RCT by Bielecki K et al used 0.5 percent GTN, however clinical value for these changes in GTN strength is uncertain.
Clinical Bottom Line
DTZ (2%) and GTN (0.2%) are equally effective in healing anal fissures. DTZ is better than GTN as it causes less side effects, and therefore better compliance and low recurrence rate. The last two studies provide additional evidence that DTZ heals approximately 50% of anal fissures resistant to GTN therapy.
- Griffin N, Acheson AG, Jonas M, Scholefield JH. The role of topical diltiazem in the treatment of chronic anal fissures that have failed glyceryl trinitrate therapy. Colorectal Dis 2002;4(6):430-5.
- Bielecki K, Kolodziejczak M. A prospective randomized trial of diltiazem and glyceryltrinitrate ointment in the treatment of chronic anal fissure. Colorectal Dis 2003;5(3)256-7.
- Kocher HM, Steward M, Leather AJM, Cullen PT. Randomized clinical trial assessing the side effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure. Br J Surg 2002;89(4):413-7.
- Jonas M, Speake W, Scholefield JH. Diltiazem heals glyceryl trinitrate-resistant chronic anal fissures: A prospective study. DIS COLON RECTUM 2002;45(8):1091-1095.