Copyright © 1999 by the European Society of Cardiology.
Cardioprotection by opening of the KATPchannel in unstable angina
Is this a clinical manifestation of myocardial preconditioning? Results of a randomized study with nicorandil
Royal Brompton and Harefield NHS Trust, London, U.K.
accepted October 14, 1998
Abstract
Aims
To assess the anti-ischaemic and anti-arrhythmic effects and overall safety of nicorandil, an ATP sensitive potassium (K+) channel opener, with ‘cardioprotective’ effects, in patients with unstable angina.
Methods
In a multicentre, randomized, double-blind, parallel-group, placebo-controlled study, oral nicorandil 20mg twice daily or a matching placebo was administered for a minimum of 48h to patients admitted with unstable angina. Treatment was standardized to include, where tolerated, oral aspirin, a beta-blocker and diltiazem. Continuous Holter ECG monitoring was performed for 48h to assess the frequency and duration of transient myocardial ischaemia and any tachyarrhythmia, as the predefined end-points of the study. A pain chart recorded the inci-dence and severity of chest pain throughout the study period. Patients with myocardial infarction identified retrospectively from troponin-T analysis were excluded.
Results
Two hundred and forty-five patients were recruited into the study. Forty-three patients were excluded with an index diagnosis of myocardial infarction, two were not randomized and 12 had unsatisfactory tape data. In the remaining 188 patients, six out of 89 patients (6·7%) on nicorandil experienced an arrhythmia, compared with 17 out of 99 patients (17·2%) on placebo (P=0·04). Three nicorandil patients experienced three runs of non-sustained ventricular tachycardia compared to 31 runs in 10 patients on placebo (P=0·087 patients;P<0·0001 runs). Three nicorandil patients had four runs of supraventricular tachycardia, compared to 15 runs in nine patients on placebo (P=0·14 patients;P=0·017 runs). Eleven (12·4%) patients on nicorandil had 37 episodes of transient myocardial ischaemia (mostly silent) compared with 74 episodes in 21 (21·2%) patients on placebo (P=0·12 patients;P=0·0028 episodes). In the overall safety analysis, which included all patients who received at least one dose of study medication, there were no significant differences in the rates of myo-cardial infarction or death between the nicorandil or placebo-treated groups.
Conclusions
Nicorandil, added to aggressive anti-anginal treatment for unstable angina, reduces transient myocardial ischaemia, non-sustained ventricular, and supraventricular arrhythmia compared to placebo. The anti-arrhythmic activity with nicorandil is probably a secondary effect resulting from its anti-ischaemic action and we suggest that this may be related to its effect on the ATP sensitive potassium channel causing pharmacological preconditioning.
Key Words: Unstable angina, nicorandil, ischaemic preconditioning
f1 Correspondence: Dr K. M. Fox, Consultant Cardiologist, Royal Brompton & Harefield NHS Trust, Sydney Street, London SW3 6NP, U.K.
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