The Analysis Of Risk Factors For Nicorandil-induced Refractory Ulcerations

Aims:Several publications have implicated nicorandil, a third-line drug for the therapy of ischemic heart disease, as a cause of idiopathic refractory ulcerations on different regions of human body. This study aimed to confirm the sites predilection of the ulcers and analyze the related factors for the ulcers in different regions, as well as making a preliminary discussion the mechanism for the development of the ulcer.Methods:Case reports of nicorandil associated ulcers were identified from the database of pubmed and cochrane library, using the key words such as nicorandil, ulcer and ulceration. The information extracted involved the case number, regions and characteristics of the ulcers, the age and gender of patients, the maximal daily dosage, administration time and cumulative dosage of nicorandil before the onset of the ulcer, and the relevant treatments, the effects of those treatments and the outcome for the ulcer. The related statistics were analyzed by using conditional binary logistic regression analysis to confirm the related factors for the ulcers in different regions.Results:Of the 192 cases of nicorandil-induced refractory ulcers (NIRU) documented, the most commonly reported ulcer was perianal ulcer (59.90%), followed by oral ulcer, parastomal ulcer, penile or vulval ulcers, gastric ulcer (jejunoileal and colonic ulcers), cutaneous ulcer consecutively. The conditional logistic regression analysis showed that compared with other ulcers, oral ulcers were negatively correlated with the patient age (odds ratio OR0.942,95%CI0.895,0.991) and the maximal daily dosage(OR0.963,95%CI0.935,0.993); perianal ulcers were positively correlated with the maximal daily dosage (OR1.084,95%CI 1.043,1.126);penile or vulval ulcers were positively correlated with the patient age (OR1.144,95%CI1.019,1.285); cutaneous ulcers were positively correlated with the administration time (OR1.013,95%CI1.001,1.024); female sex was the risk factor for the parastomal ulcers (OR0.103,95%CI0.012,0.859).Conclusion:Of the NIRUs, perianal ulcer was the most common type. The ulcers were resistant to various kinds of local and systemic treatments and the only treatment of value was the discontinuation of the drug. The development of the ulcer was related with the age and maximal daily dosage mainly.