Chronic anal fissure: 2% topical diltiazem hydrochloride

Sanei et al. 2009

In this RCT, 102 adults (mean age 30 years, range 17–61 years) with symptoms of anal fissure for more than 6 weeks or presence of a sentinel anal tag were randomised in equal numbers to receive 2% topical diltiazem ointment or 0.2% glyceryl trinitrate ointment, both applied twice daily for 12 weeks^[14]. Participants were not prescribed stool softeners or bulk laxatives. Allocation concealment was not discussed but the study was double blind.

Fissure healing (defined as complete skin closure over the fissure, confirmed by anoscopy) at 12 weeks occurred in 66.7% of participants in the diltiazem group and in 54.9% of participants in the glyceryl trinitrate group (p=0.2). Mean time to complete healing was 7.58±2.01 weeks in the diltiazem group and 4.85±1.84 weeks in the glyceryl trinitrate group (p=0.001). Recurrence rates were not reported.

Abd Elhady et al. 2009

In this RCT 160 adults (mean age 34 years, range 17–70 years) with anal fissure (duration of symptoms not stated) were randomised in equal numbers to 4 treatment groups: internal lateral sphincterotomy, 2% topical diltiazem ointment twice daily for 4–6 weeks, 0.2% glyceryl trinitrate ointment twice daily for 4–6 weeks, or botulinum toxin injection^[15]. Allocation concealment was not discussed. Participants who were lost to follow-up were excluded and replaced by new participants receiving the same treatment.

Fissure healing was defined as complete re-epithelialisation of the fissure and absence of symptoms. At 8 weeks, 80% of participants receiving diltiazem ointment showed complete healing, compared with 95% who had sphincterotomy surgery and 90% of those receiving glyceryl trinitrate (data for participants receiving botulinum toxin were not reported, statistical significance not reported).

The average time to fissure healing was 5.1±1.13 weeks in the diltiazem group and 5.0±1.1 weeks in the glyceryl trinitrate group. The time to healing in all groups was similar and not statistically significant (p=0.067). Of the 40 participants in each treatment group, recurrence occurred in 26 participants (65%) in the diltiazem group compared with 4 (10%) in the sphincterotomy surgery group, 23 (57.5%) in the glyceryl trinitrate group and 21 (52.5%) in the botulinum toxin group (statistical significance not reported). The average time to recurrence was not reported.

Samim et al. 2012

In this RCT, 134 adults (mean age 46±16 years) with anal fissure for more than 4 weeks were randomised to receive either 2% topical diltiazem cream applied twice daily for 3 months combined with placebo injection (n=74), or botulinum toxin injection with placebo cream for 3 months (n=60)^[16]. Allocation concealment was not discussed. The study was stated to be double blind but although participants were randomised, treatment days were also randomised to botulinum toxin or placebo so that the same vial of botulinum toxin was used for treating 4 people. Analysis was by intention to treat.

Fissure healing was defined as epithelialisation or macroscopic healing after 3 months. Healing rates were the same in both groups (43% in each, p=0.992). During a median follow-up time of 39 months, 17.6% of participants randomised to diltiazem cream experienced recurrence of fissure compared with 11.7% of participants randomised to botulinum toxin (p=0.469).

Suvarna et al. 2012

In this RCT, 200 adults (mean age 40 years, range 18–65 years) with anal fissure for more than 8 weeks were randomised in equal numbers to receive 2% topical diltiazem ointment twice daily for 6 weeks or surgical sphincterotomy^[17]. Allocation concealment was not discussed. Twelve participants dropped out of the study (9 from the diltiazem group and 3 from surgical group) and were not included in the analysis.

Fissure healing (complete disappearance of fissure on examination) was observed by 6 weeks in 69.23% of the diltiazem group compared with 95.87% in the surgery group (statistical significance not reported). Recurrence 2 months after treatment was reported in 6 out of 58 (10.43%) participants in the diltiazem group compared with none of the 89 participants in the surgery group.

Cevik et al. 2011

In this RCT, 93 children (mean age 32 months, range 2–144 months) with anal fissure for more than 15 days were randomised to receive topical treatment with 2% diltiazem ointment, 0.2% glyceryl trinitrate ointment or 10% lidocaine ointment, applied twice daily for 8 weeks^[18]. Children with constipation also received lactulose, a sitz bath twice a day, toilet training and dietary regulation. Allocation concealment was not discussed but the study was double blind. If healing had not occurred by 8 weeks, the same 8-week treatment was offered again.

Nine children were lost to follow-up and 2 experienced dermatitis and withdrew from the study (1 in the diltiazem group and 1 in the glyceryl trinitrate group); these 11 children were excluded from the analysis. After the first 8-week treatment course, the healing rate in the diltiazem group was 82.1% (23 out of 28), which was statistically significantly higher than that in the other treatment groups: 39.3% (11 out of 28) in the glyceryl trinitrate group and 25.0% (7 out of 28) in the lidocaine group (p<0.0001).

After a repeated 8-week course, the healing rate in the diltiazem group was 92.9% compared with 82.1% in the glyceryl trinitrate group and 64.3% in the lidocaine group (p<0.05). If the anal fissures had not healed after 2 courses, treatment was switched to topical diltiazem for an additional 8 weeks; all children were symptom-free after this third treatment course. The recurrence rate during 1-year follow-up was 11.1% in the diltiazem group compared with 37.0% in the glyceryl trinitrate group and 57.1% in the lidocaine group (statistical significance not reported).