Glyceryl Trinitrate Ointment for the Treatment of Chronic Anal Fissure Results of a Placebo-Controlled Trial and Long-Term Follow-Up M. L. Kennedy, B.Sc.(Hons), S. Sowter, M.B.B.S., H. Nguyen, F.R.A.C.S., D. Z. Lubowski, F.R.A.C.S. From the Department of Colorectal Surgery, St. George Hospital, Sydney, Australia PURPOSE: A randomized, double-blind, placebo-controlled trial was performed to test the effect of intra-anal glyceryl trinitrate ointment in patients with chronic anal fissures that would normally have been treated by sphincterotomy. Long-term follow-up was then performed to assess fissure healing. METHODS: Patients with chronic anal fissures were randolrdy assigned to 0.2 percent topical glyceryl trinitrate ointment or placebo. Anal manometry was performed be- fore treatment, one week later, and 48 hours after treatment ceased at four weeks. Fissure healing was assessed by" an observer blinded to the treatment arm. Pain was recorded on a linear analog scale. At the completion of the trial, treatment was continued with glyceryl trinitrate until fis- sure healing was obtained or lateral sphincterotomy was performed if required for ongoing pain. A long-term fob low-up assessment was made at a mean of 29 (range, 25-33) months. RESULTS: There was a significant reduction in anal resting pressure at Week t with glyceryl trinitrate (P = 0.001) but not placebo, and at Week 4 there was a signifi- cant reduction in pain score with glyceryl trinitrate (P = 0.001) and placebo (P = 0.01) and a significant reduction in fissure grade with glyceryl trinitrate (P = 0.0001) and pla- cebo (P = 0.02). Forty-six percent of fissures healed with glyceryl trinitrate and 16 percent healed with placebo (P = 0.001). At long-term follow-up in 40 of 43 patients, 14 patients (35 percent) had undergone lateral sphincterot- omy, and in the remainder who were treated with glyceryl trinitrate there was a significant reduction in pain score (P = 0.0002). Seventeen patients attended for repeat ma- nometry and fissures were healed with glyceryl trinitrate in ten (59 percent) cases. High internal sphincter pressures persisted at long-term follow-up in patients successfully treated with glyceryl trinitrate, indicating that the sphincter is the cause rather than effect of anal fissure. CONCLUSION: Topical glyceryl trinitrate produces a successful internal sphincterotomy, which resulted in long-term healing of 59 percent of chronic anal fissures and significant improve- merit in pain. Internal sphincter spasm is the cause of chronic anal fissure. [Key words: Glyceryl trinitrate; Anal fissure] M. L. Kennedy, S. Sowter, and H. Nguyen were supported by the Colorectal Research Fund and Department of Surgery, St. George Hospital, Sydney, Australia. Presented at the Tripartite Meeting, London, United Kingdom, July 8 to 10, 1996. Address reprint requests to Dr. Lubowski: St. George Medical Cen- tre, 1 South Street, Kogarah, Sydney, NSW 2217 Australia. Kennedy ML, Sowter S, Nguyen H, Lubowski DZ. Glyceryl trinitrate ointment for the treatment of chronic anal fissure: results of a placebo-controlled trial and long-term follow-up. Dis Colon Rectum 1999;42:1000-1006. T he link between internal sphincter spasm and anal fissure was established some years ago. 1, ~ More recently it has been shown that anal fissures are ischemic ulcers with reduced mucosal blood supply caused by the high internal sphincter tone. 3 Anal dilation 4 and lateral internal sphincterotomy 5 are ef- fective treatments for chronic anal fissure. Both these procedures may result in permanent incontinence of varying severity; however, reversible chemical sphincterotomy using topical glyceryl trinitrate (GTN) as a nitric oxide donor seemed an attractive method of treatment.< 7 There are now several uncontrolled studies s-l° and two randomized trials 11, ~2 that showed healing of chronic anal fissures using topical GTN, but fissure recurrence rates and long-term results are un- known. In this article we report a randomized, dou- ble-blind, placebo-controlled trial and long-term fol- low-up results. PATIENTS AND METHODS Between February and August 1993 forty-three consecutive patients with chronic anal fissure were entered into the trial. Symptoms had been present in each patient continuously for at least three months and were severe enough to have otherwise warranted surgical sphincterotomy. Patients were randomly as- signed to receive either topical GTN or placebo using a system of sealed envelopes. Twenty-four patients received GTN (male/female ratio, 10/14; mean age, 37; standard deviation, 16; range, 19--85 years), and t9 patients received placebo (male/female ratio, 10/9; mean age, 42; standard deviation, 12; range, 27-65 years). 1000