Glyceryl trinitrate ointment for the treatment of chronic anal fissure: results of a placebo-controlled trial and long-term follow-up.

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 randomly assigned to 0.2 percent topical glyceryl trinitrate ointment or placebo. Anal manometry was performed before 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 fissure healing was obtained or lateral sphincterotomy was performed if required for ongoing pain. A long-term follow-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 1 with glyceryl trinitrate (P = 0.001) but not placebo, and at Week 4 there was a significant 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 placebo (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 sphincterotomy, 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 manometry 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 improvement in pain. Internal sphincter spasm is the cause of chronic anal fissure.