The role of Nicorandil in non-healing surgical wounds

Abstract

We report two patients with non-healing surgical wounds, which healed after the withdrawal of Nicorandil therapy. Nicorandil should be recognised as an aetiological factor for non-healing wounds or ulcers once other inflammatory and malignant causes have been excluded. This may avoid surgery for high-risk patients and may also reduce complications for patients who undergo surgery for non-healing wounds. As Nicorandil is used in patients with severe coronary artery disease, it is recommended that the advice of a cardiologist is sought prior to cessation or adjustment to its dose.

Role of nicotinic acid and nicotinamide in nicorandil‐induced ulcerations: from hypothesis to demonstration

“…Five years later, Watson et al (6) described anal ulcers. Since then, many reports of single or multiple nicorandil-induced ulcerations (NIUs) in oral, anal, perianal, vulvovaginal, perivulval, penile, gastrointestinal, colonic, peristomal, skin and ocular locations have been reported (7)(8)(9)(10)(11)(12)(13)(14)(15). Fistulae are now being investigated (16).…”

“…NIUs mostly occur at vulnerable sites, being peristomal after any procedure that creates a stoma, penile after circumcision and perianal after haemorrhoidectomy. Under cardiologists' aegis, nicorandil replacement by a classic NO donor can be done without complication (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Nicorandil ulcer: moves beyond the mucosa

“…13 Two unconvincing hypotheses have been put forward: (i) a toxic metabolite of nicorandil excreted in the gut; and (ii) a vascular steal phenomenon. However, nicorandil metabolites are mostly excreted through the kidneys and the toxic metabolite hypothesis would not explain the abdominal wounds in the case presented by Riddell et al 9 Likewise, it is hard to rationalise the steal phenomenon, since the sites are typically well vascularised, the surrounding skin looks healthy and histological support is lacking. A more likely explanation is that nicorandil, in a dose-dependent manner, dephosphorylates myosin and so hinders the actin filament contraction that is necessary for cell migration, as would be required to repair mucosal microtrauma and surgical wounds.…”

“…Mosley et al 8 describe a patient who almost died from haemorrhage as a consequence of progressive peri-anal mucosal ulceration induced by nicorandil. Riddell et al 9 show for the first time that nicorandil can also prevent the healing of surgical wounds, one case involving otherwise normal non-mucosal tissue. While these reports are of interest, the potential for nicorandil to prevent wound healing is noteworthy, as this extends the association beyond the mucosae.…”

Authors' reply to Herxheimer

“…7 Wound healing may also be delayed in patients taking this drug. 8 These multiple reports, from the UK and around the world, cannot be discounted as chance associations. As dermatologists, we do not feel qualified to comment on whether we can do without nicorandil.…”