Fast track — ArticlesEffect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised triala
Introduction
Stable angina affects 2·3–5·1% of men aged 40–59 years, and more than 10% of those older than 60 years.1 In the UK, 25% of all deaths are attributable to coronary heart disease, and 25% of all patients presenting with a first myocardial infarction have a history of stable angina.2 Therefore, stable angina is important, not only as a cause of disability, but also as a frequently observed marker for underlying coronary heart disease. Aspirin, angiotensin converting-enzyme (ACE) inhibitors, and statins reduce the risk of cardiovascular events in subgroups of patients with stable angina;3, 4, 5, 6, 7 however, the effect of specific antianginal treatment on morbidity and mortality in patients with stable angina remains unknown.
Nicorandil is a nicotinamide ester with a dual mechanism of action. Its distinctive pharmacological effect is to open ATP-sensitive potassium channels (KATP), thereby dilating peripheral and coronary resistance arterioles; but it also possesses a nitrate moiety which dilates systemic veins and epicardial coronary arteries. Thus, nicorandil increases coronary blood flow, reduces preload and after-load,8, 9, 10, 11 and has an antianginal efficacy and safety profile similar to that of oral nitrates, β-blockers, and calcium antagonists.12, 13, 14 However, in addition to relieving symptoms of ischaemia, nicorandil has potential cardioprotective effects. These effects are probably due to its ability to mimic the powerful ischaemic preconditioning phenomenon by opening KATP channels, as shown in clinical and preclinical studies.15, 16, 17, 18, 19
The objective of the Impact Of Nicorandil in Angina (IONA) study was to investigate whether or not cardioprotective effects of nicorandil could be shown in a large outcome study in stable angina.
Section snippets
Patients
The design and conduct of the IONA study has been reported in detail previously.20 Briefly, patients with a history of angina were recruited from centres in the UK. Angina could be recently diagnosed, but not unstable or chronic. Standard background antianginal therapy was not specified, but was to be optimum treatment as judged by the investigator for the individual patient. Such treatment could include one or more oral antianginal medications including β-blockers, calcium-channel blockers, or
Results
5126 patients were enrolled from 226 centres in the UK between May, 1998, and August, 2000. 2565 were randomly assigned nicorandil and 2561 placebo (figure 1). Patients were recruited in about equal numbers from primary care and hospital practices. The mean follow-up was 1·6 years (SD 0·5), with the final study visit in August, 2001. The baseline characteristics of randomised participants and the cardiovascular medications being taken at randomisation are listed in Table 1, Table 2,
Discussion
In the IONA study, we report a significant improvement in outcome from antianginal treatment in patients with stable angina. Outcome was defined as a combination of morbidity and mortality by a composite primary endpoint of coronary heart disease death, non-fatal myocardial infarction, or unplanned hospital admission for chest pain. Event rates in all components of the primary endpoint were lower in patients on nicorandil than on placebo and therefore each contributed to the significance of the
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