Use of nicorandil in cardiovascular disease and its optimization.

Nicorandil, a unique dual pharmacological mechanism anti-anginal agent with adenosine triphosphate sensitive potassium (K(ATP)) channel agonist and nitrate-like properties, provides cardiologists with a means of managing angina pectoris patients effectively and provides long-term cardioprotection. The aim of this review is to provide an update on the efficacy of treatment with nicorandil, which counteracts cardiac damage in patients with acute or chronic ischaemic heart disease, congestive heart failure and arrhythmia, with particular emphasis on that induced by ischaemic preconditioning (in which strong protection against ischaemia-reperfusion injury is afforded by a brief preliminary ischaemic period). First, the rationale for nicorandil treatment and its pharmacological effects on the vasculature and cardiomyocytes are reviewed. The mechanisms underlying ischaemic preconditioning, with a focus on those that involve the K(ATP) channel pathway, such as mitochondrial permeability transition pores, sub-lethal reactive oxygen species generation and nitric oxide production are then discussed. Next, clinical practice related to ischaemic preconditioning and pharmacological preconditioning with nicorandil as well as other favourable mechanisms of improvement of prognosis, in which it plays a role in improving endothelial function, modulating autonomic nervous system activity and stabilizing plaque are summarized. Finally, the tolerability of nicorandil is discussed.