Glyceryl trinitrate for chronic anal fissure - Healing or headache? Results of a multicenter, randomized, placebo-controlled, double-blind trial

PURPOSE: Internal anal sphincterotomy for treating chronic anal fissure can irreversibly damage anal continence. Reversible chemical sphincterotomy ma y be achieved by anal application of glyceryl trinitrate ointment (nitric o xide donor), which has been reported to heal the majority of patients with anal fissure by inducing sphincter relaxation and improving anodermal blood flow. This trial aimed to further clarify the role of glyceryl trinitrate in the treatment of chronic anal fissure. METHODS: A total of 132 consecuti ve patients from nine centers were randomly assigned to receive 0.2 percent glyceryl trinitrate ointment or placebo twice daily for at least four week s. The severity of pain and maximum anal resting pressure were measured bef ore and after one week of treatment, Anodermal blood now was measured befor e and after application of glyceryl trinitrate or placebo in ten patients. RESULTS: The study was completed by 119 patients (59 glyceryl trinitrate an d 60 placebo), matched for gender, age, duration of symptoms, duration of t reatment, site of fissure, previous attempts to treat, pain score, and maxi mum anal resting pressure. Twenty-nine patients (49.2 percent) healed after glyceryl trinitrate and 31 patients (51.7 percent) healed after placebo (P = not significant). Pain score fell significantly in both groups, in addit ion to maximum anal resting pressure. Anodermal blood flow improved signifi cantly in seven patients receiving glyceryl trinitrate, but not in the thre e receiving placebo. Twenty-three patients (33.8 percent) experienced heada che and 4 (5.9 percent), orthostatic hypotension after glyceryl trinitrate. CONCLUSION: This trial fails to demonstrate any superiority of topical 0.2 percent glyceryl trinitrate treatment vs. a placebo, although the effects of glyceryl trinitrate on anodermal blood flow and sphincter pressure are c onfirmed. This finding, together with the high incidence of side-effects, s hould discourage the use of this treatment as a substitute for surgery in c hronic anal fissure.