Innovations in chronic anal fissure treatment: A systematic review

Table 1 Studies comparing healing and recurrence rates of different pharmacological therapies

S/N	Ref.	Study details	Healing	Remarks
1	Lund et al[17] 1997 Double armed, prospective, randomized	0.2% GTN vs placebo 80 patients	GTN-68% healing rate within 8 wk Placebo-8% healing rate Recurrences-7.9% in GTN group. Treated successfully with additional 6 wk of GTN
2	Kennedy et al[18] 1999 Double arm, prospective, randomized, placebo-controlled	0.2% GTN vs placebo 43 patients	GTN group-46% healing rate Placebo group-16% healing rate	Statistically significant
3	Altomare et al[19] 2000 Double arm, prospective, randomized	0.2% GTN vs placebo 132 patients	GTN-49.2% healing rate Placebo-51.7% healing rate Recurrence-19% in GTN group	Failed to establish superiority of GTN over placebo
4	Scholefield et al[20] 2003 Four armed, prospective, randomized	0.1% GTN vs 0.2% GTN vs 0.4% GTN vs placebo 200 patients	Intention-to-treat analysis: Placebo-37.5% healing rate 0.1% GTN-46.9% healing rate 0.2% GTN-40.4% healing rate 0.4% GTN-54.1% healing rate	High placebo healing rates noted-possibly due to inclusion of acute fissures Lowest healing rate with 0.2% GTN likely due to anomaly due to small sample size
5	Kocher et al[23] 2002 Double arm, prospective, randomized	0.2% GTN vs 2% Diltiazem cream 61 patients	GTN-25/29 (86.2%) patients improved or healed Diltiazem-24/31 (77.4%) patients healed or improved
6	Knight et al[27] 2001 Single arm, prospective, non-randomized	2% Diltiazem cream for chronic anal fissures 71 patients	59/66 (89.4%) patients healed within 16 wk 7/59 (11.8%) patients on follow-up developed recurrences
7	Carapeti et al[25] 2002 Two separate pilot studies	2% Diltiazem cream vs 0.1% bethanechol gel 30 patients	Diltiazem-67% healing rate Bethanechol-60% healing rate
8	Jonas et al[26] 2002 Single arm, prospective, non-randomized	Topical 2% Diltiazem for fissures failing GTN therapy 39 patients	49% healing rate
9	Maria et al[21] 1998 Double arm, prospective, randomized	Botulinum toxin 20 units vs saline 30 patients	Botulinum toxin-11/15 (73.3%) patients healed at 2 mo. Remaining 4 patients (26.7%) healed after additional 25 units Saline-2/12 patients healed at 2 mo No recurrences in the botulinum group
10	Lindsey et al[24] 2003 Single arm, prospective, non-randomized	Botulinum toxin 20 units injection for non-healing anal fissures after initial 8 wk of 0.2% GTN 40 patients	43% complete healing 12% unhealed with symptom resolution 18% unhealed with symptom improvement 27% unhealed with no symptom improvement 27% underwent eventual surgery
11	Brisinda et al[22] 1999 Dual arm, prospective randomized, non-controlled	Botulinum toxin 20 units injection vs 0.2% GTN for 8 wk Failure to heal after 8 wk-treatment offered from the other arm 50 patients	Botulinum toxin–96% healed fissures after 2 mo 0.2% GTN-60% healed fissures after 2 mo	Statistically significant
12	Jones et al[28] 2006 Dual arm, prospective randomized, non-controlled	Botulinum toxin 25 units injection and 0.2% GTN vs Botulinum toxin 25 units alone 30 patients	Botulinum toxin and GTN-47% complete healing at 8 wk Botulinum toxin alone-27% complete healing Botulinum toxin and GTN-27% treatment failure by 6 mo Botulinum toxin alone-47% treatment failure by 6 mo	Not statistically significant Not statistically significant
13	Garrido et al[8] 2007 Single arm, prospective, non-randomized	Gonyautoxin 100 units injection 23 patients	18/23 patients-healed in 7 d 3/23-healed in 12 d 2/23 patients-healed in 14 d

GTN: Glyceryl trinitrate.