Nicorandil and calcium antagonists: remember oro-anal ulceration and reflux cough too

Editor– Tarkin et al (Clin Med February 2013 pp63–70) have comprehensively reviewed the current drug treatment options in stable angina. With regard to their comment on nicorandil and calcium antagonists, it is worth reminding physicians of other commonly occurring side effects that may limit the ability of patients to take such medications in the long term.

With nicorandil, severe (but reversible on stopping the drug) oral¹ or perianal ulceration are both well described and can significantly impair compliance with the drug. A recent survey estimated 1 in 250 patients get anal ulcers, which requires discontinuing treatment.² In more serious cases, ulcers progress to fistulae into adjacent organs.³ The mechanism is, as yet, unclear but may involve the effects of nicotinic acid on causing ulceration in the epithelium of healing wounds.⁴

With calcium antagonists, an underappreciated problem is reflux cough⁵ due to attenuation of the lower oesophageal sphincter and reduced oesophageal clearance. Discontinuation of the drug for up to 3 months may be necessary. Reflux cough should be particularly suspected with cough on phonation, throat clearing after meals, or cough on rising/stooping (without dyspeptic symptoms).⁶ In studies, verapamil and amlodipine seem to cause more reflux symptoms than diltiazem.⁷

In summary, be aware that a patient on nicorandil may present with unexplained oro-anal ulceration and, unless the offending drug is stopped, the ulcer may worsen and lead to fistulae. Regarding patients on calcium antagonists, discontinuation of the drug may be needed if reflux cough persists.