Perianal versus endoanal application of glyceryl trinitrate 0.4% ointment in the treatment of chronic anal fissure: results of a randomized controlled trial. Is this the solution to the headaches?

BACKGROUND

Application of nitroglycerin (glyceryl trinitrate) ointment with perianal administration is a widely used treatment for chronic anal fissure. However, headache occurs after application in 20% to 70% patients and leads to withdrawal in 10% of patients.

OBJECTIVE

The aim of the study was to investigate whether endoanal application of the ointment may lower the frequency of headaches without sacrificing effectiveness. compare the effects of perianal versus endoanal administration of nitroglycerin ointment on frequency of headache and rate of healing in the treatment of chronic anal fissure.

DESIGN

This was a prospective randomized clinical trial (ClinicalTrial.gov, NCT01132391).

SETTINGS AND PATIENTS: Study participants were consecutive patients with a diagnosis of chronic anal fissure treated at a university teaching hospital in Elche, Alicante, Spain.

INTERVENTION: Patients were randomly assigned to receive perianal (n = 26) or endoanal (n = 26) administration of 0.4% nitroglycerin ointment (375 mg of ointment containing 1.5 mg of glyceryl trinitrate), applied every 12 hours over an 8-week period.

MAIN OUTCOME MEASURES: The primary endpoint of the study was the number of patients with headache within 3 hours after application of the ointment, analyzed with the intention-to-treat principle. Intensity of headache pain was rated on a 10-point visual analog scale. Secondary endpoints included frequencies of fissure healing, anorectal pain, rectal bleeding, pruritus, and incontinence.

RESULTS

Headaches were reported in 14 (54%) patients with perianal treatment and in 6 patients (23%) with anorectal treatment (p = 0.003). The median headache pain score was 6 (range, 0-10) in the perianal group and 4.5 (range, 0-10) in the endoanal group (p = 0.03). Disabling headaches led to crossover from perianal to endoanal treatment in 4 patients (15%), and from endoanal to perianal treatment in 1 patient (4%) (p = 0.004). Of the 4 patients who switched from perianal to endoanal treatment, 2 reported improvement in headaches and 2 stopped treatment. The patient who switched from endoanal to perianal treatment also showed no improvement and stopped treatment. The healing rate at 24-week follow-up was 62% (16 patients) with perianal treatment and 77% (20 patients) with endoanal treatment (p < 0.05).

LIMITATIONS: Effects on sphincter pressure were not evaluated because manometric measurements were not available.

CONCLUSIONS

Endoanal application significantly reduces the frequency of headaches due to treatment with 0.4% nitroglycerin ointment and results in a higher healing rate compared with perianal administration. However, roughly 1 in 4 patients still experiences headaches. Our data suggest that endoanal application may be a better option for treatment of anal fissure with nitroglycerin ointment.