Evidence strengths and limitations

Evidence strengths and limitations

This summary is based on evidence from a Cochrane review of 4 RCTs[27] and 5 additional RCTs[28],[29],[30],[31],[32]. These sources presented similar conclusions although their precise estimates of effect varied.

None of the studies compared 2% topical diltiazem with 0.4% topical glyceryl trinitrate (the licensed strength), which limits the conclusions which can be drawn regarding comparative efficacy and risk of adverse effects, especially headache. Although several of the 5 additional RCTs included a power calculation, they were relatively small. Most were conducted in countries outside northern Europe (for example, Egypt[29], India[31], Iran[28], and Turkey[32]), as well as the Netherlands[30], but the findings are still likely to be applicable to the UK population because of the simple nature of the treatment.

The studies showed some degree of heterogeneity in terms of their definition of chronic fissure: treatment duration; concurrent treatments (such as a high-fibre diet or use of laxatives), child or adult populations, methods and time points for assessing fissure healing, and length of follow-up to assess recurrence. This may partly explain the large variation in the estimates of healing and recurrence observed in the RCTs, in addition to random sampling error.

The long-term efficacy, safety and fissure recurrence while using topical diltiazem was not assessed in the RCTs because most patients underwent surgery after first recurrence or healed completely and left the studies. The authors of the Cochrane review note the relapsing-remitting nature of chronic anal fissure and suggest that short follow-up periods may give rise to misleading results[27].

[27] Nelson RL, Thomas K, Morgan J et al. (2012) Non surgical therapy for anal fissure. Cochrane Database of Systematic Reviews issue 2: CD003431

[31] Suvarna R, Panchami, Guruprasad RD (2012) Chemical sphicterotomy versus surgical sphicterotomy in the management of chronic fissure in ANO: A prospective, randomized trial. Journal of Clinical and Diagnostic Research 6: 1018–21