Nicorandil: a drug for many purposes: too good to be true?

Nicorandil, a drug approved for the treatment of ischaemic heart disease, is believed to have a dual properties. The intrinsic mechanism of the drug (selective activation of KATP channels at the sarcolemmal and mitrochondrial level) allows coronary and peripheral vasodilatation with subsequent reduction of preload and afterload. Secondly, because of the role KATP channels in ischaemic preconditioning, nicorandil has been attributed cardioprotective effects. The drug has been available in Europe for years, classified as a new class of therapy for coronary artery disease, but failed till now to truly penetrate on the ‘European market’. The large scaled, randomized IONA trial evaluated the efficacy of nicorandil on top of ‘conventional’ antianginal drugs for the treatment of stable angina pectoris. The primary end-point (a composite of cardiac death, myocardial infarction, unplanned hospital admission for chest pain) occurred significantly less in the nicorandil (13.1%) then in the placebo group (15.5%, P=0.014). Nevertheless, only about half of patients were on -blockers and ‘unplanned hospital admission for chest pain’ is a very weak endpoint despite the randomized character of the trial. Inherent of these limitations, nicorandil may be considered as a safe additional drug to -blockers for angina relief in patients with stable angina pectoris. Weather, it may be an alternative to -blockers in post myocardial infarction patients remains to be established. Nicorandil has a long tradition in Japan, where it has been studied extensively. The present issue of the journal publishes two papers from Japan. The first study by Matsuo et al. evaluates again the efficacy of nicorandil in ischaemic preconditioning in the human angioplasty model while the second paper by Izawa et al. investigates the impact of the drug on left ventricular filling pressures in exercising patients with hypertrophic cardiomyopathy. A potential benefit of the drug is demonstrated in both trials, characterized by a heavy, ‘high-tech’ methodology applied to small study cohort. Nevertheless, they merit our consideration as both authors have improved and extended prior research in the field, providing thereby relatively solid data. Matsuo et al. previously demonstrated by simple ST-segment analysis that nicorandil enhances preconditioning in the human PTCA model. However, the potential contribution of collateral blood flow was not adequately assessed. In the present study, a homogeneous group of 44 patients with isolated proximal LAD stenosis and normal left ventricular function, was randomized to intravenous nicorandil or saline prior to angioplasty. In addition to STsegment analysis, Tc tetrofosmin SPECT acquisition was performed at the end of the PCTA as a surrogate for myocardial perfusion to the related myocardium. A trend but no significant flow increase to the ischemic bed was demonstrated together with a significant attenuation of STsegment elevation in the nicorandil group. This implies that nicorandil seems to possess a cardioprotective effect independent of myocardial * Corresponding author: Tel.: +41/21-3140-012; fax: +41/213-140-067 E-mail address: [email protected] (E. Eeckhout). European Heart Journal (2003) 24, 1282–1284