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Diltiazem cream (2%) is better than Glyceryltrinitrate cream (0.2%) in management of chronic anal fissure

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]

Clinical Scenario

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.

Search Strategy

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.

Search Outcome

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.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Griffen N,
47 adult patients with chronic anal fissure that had failed treatment with 0.2% GTN creamProspective StudyEfficacy of treatmentAt 8 week, 46 patients completed course of DTZ cream, out of these 22 (48%)had healed fissure .No randomization
Side effect of treatmentPerianal itching was noted by all patient.
RecurrenceAt 44.9 weeks (median duration of follow up) 2 patients had recurrence of symptomatic anal fissure
Bielecki K,
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%) ointmentPRCTEfficacy of treatmentIn 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 treatmentIn group A, 7 out of 21 patients (33.3%) experienced side effects mainly headache whereas no side effects were noted in group B.
Kocher HM,
60 adult patients with chronic anal fissurePRCTEfficacy of treatmentAt 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 treatmentAfter 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)
RecurrenceAt 12 week, 2 patients has recurrence after healing in the GTN group, whereas none of the patients in the DTZ group had such recurrence.
Jonas M,
39 adult patients with chronic anal fissure that had failed treatment with 0.2 percent GTN creamProspective StudyEfficacy of treatmentAt 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 treatment3 patients (7.8%) reported itching, one patient (3.9%) developed headache, drowsiness and mood swings
RecurrenceAt 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.


  1. 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.
  2. 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.
  3. 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.
  4. 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.