Topical treatments for anal fissure

Clinical question

How effective are topical treatments (calcium channel blockers [CCBs], nitrates, and vitamin E) for chronic anal fissures in adults?

Bottom line

Healing rates with topical nitroglycerin are roughly 60% versus 40% with placebo at 8 weeks. Topical CCBs are at least as good as nitroglycerin, with a lower risk of headache (7% versus 56%). Based on 1 RCT, topical vitamin E may be superior to nitroglycerin (86% versus 66% healed at 8 weeks).

Evidence

Five meta-analyses of RCTs from the past 10 years were identified.^1-5 Adjunctive treatments were usually unclear (often fibre therapy or dietary advice). Healing was defined based on examination findings or patient report. Results were statistically significant unless indicated.

• Calcium channel blockers (eg, 2% diltiazem ointment): In 3 systematic reviews (1 to 7 RCTs, 60 to 727 patients), at about 6 weeks, 78% to 82% of patients were healed with CCBs versus 33% to 42% with control; number needed to treat (NNT)=3 (1 of the 3 analyses was not statistically different).^1-3

• Nitroglycerin (eg, nitroglycerin 0.2% to 0.4% ointment): In 17 RCTs (1063 patients), at 8 weeks,¹ 63% of patients were healed versus 38% placebo; NNT=4.

  • - Other systematic reviews found efficacy to be about 50% versus 35% placebo.^2,3

• Calcium channel blockers versus nitroglycerin: In 11 RCTs (770 patients), at 8 weeks, 79% of patients were healed with CCBs versus 65% with nitroglycerin.¹ Similar results were found in other systematic reviews^3-5 but were statistically different in only 1.³

  • - In 10 RCTs (590 patients), 7% had headache with CCBs versus 56% with nitroglycerin.¹

• Vitamin E: In 1 RCT (160 patients, twice daily treatment),⁶ at 8 weeks, 86% were healed with vitamin E versus 66% with nitroglycerin; NNT=5. None stopped vitamin E owing to headache versus 18% with nitroglycerin.

• Limitations: Some reviews included pediatric populations or did not include all RCTs. Many RCTs were unblinded, underdosed nitroglycerin, or had unclear vitamin E doses.

Context

• Guidelines recommend topical CCBs.⁷ Botulinum toxin injections and surgery are options for treatment failure, but fecal incontinence is possible.⁷

• For an 8-week treatment, compounded topical CCBs or nitroglycerin cost roughly $60 per 30 g (personal communication from Stacy Jardine, Clinical Pharmacist, Peace River Value Drug Mart in Peace River, Alberta; 2022). Commercially available vitamin E ointment costs about $10 per 50 g.⁸

Implementation

Anal fissures are commonly found in middle-aged adults and in children.⁹ They are primarily diagnosed by clinicians, with symptoms including pain during or after passage of stool, rectal bleeding, and linear tear (with or without a sentinel tag).¹⁰ Most fissures are at the midline. Fissures not in the midline should be investigated for secondary causes (eg, Crohn disease).¹¹ Differential diagnosis of severe anal pain includes fissure, thrombosed hemorrhoids, or perirectal abscess.⁹ Rectal bleeding is not necessarily diagnostic of malignancy but requires assessment and consideration of other risks factors.¹²