Nicorandil is a
drug with both
nitrate-like and
ATP-sensitive potassium-channel (K+
ATP) activating properties. By virtue of this dual mechanism of action, the
drug acts as a balanced coronary and peripheral
vasodilator and reduces both preload and afterload. The K+
ATP channel has been shown to be involved in the phenomenon of myocardial preconditioning, and studies in animal models of ischaemia-reperfusion-induced
myocardial stunning or
infarction indicate that
nicorandil has cardio-protective effects. Studies in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) have shown that the administration of
nicorandil reduces ST-segment elevation during ischaemia.
Nicorandil significantly improved the results of exercise tolerance tests versus baseline in patients with stable effort
angina pectoris in early noncomparative trials. The
drug also improved the results of exercise tolerance tests relative to placebo in early randomised, double-blind, placebo-controlled trials. In randomised, double-blind comparative studies in patients with
angina pectoris,
nicorandil has demonstrated equivalent efficacy, as measured by exercise tolerance testing, to
isosorbide di- and mononitrate,
metoprolol,
propranolol,
atenolol,
diltiazem,
amlodipine and
nifedipine. The effects of
nicorandil on various aspects of myocardial recovery from ischaemic damage caused by acute
myocardial infarction have been investigated in the short term. Regional left ventricular (LV) wall motion, a marker of myocardial function, was significantly improved in
nicorandil recipients relative to control. The main adverse event associated with
nicorandil as treatment for
angina pectoris is
headache. This can be minimised by commencing
nicorandil at a low dose in patients prone to
headache. There have been infrequent case reports of
mouth ulcers in patients receiving
nicorandil; causality has not been conclusively established, but product prescribing information indicates that an alternative treatment should be considered if persistent aphthous or severe mouth ulceration occurs. Thus,
nicorandil remains a useful background
therapy for patients with
angina pectoris. The
drug has also demonstrated potential cardioprotective effects when used as part of an intervention strategy directly after acute
myocardial infarction in high-risk patients. Further large scale longer term studies of
nicorandil in this latter indication are awaited with interest.