Effect of Nicorandil on Coronary Events in Patients with Stable - IONA

Description:

Does nicorandil reduce the frequency of coronary events in men and women with stable angina?

Hypothesis:

Nicorandil will reduce the frequency of coronary events in patients with stable angina.

Study Design

Study Design:

Primary Endpoints:

The frequency of primary composite endpoint (coronary heart disease death, nonfatal myocardial infarction, or unplanned hospital admission for cardiac chest pain)

Secondary Endpoints:

Secondary composite end-point event was coronary heart disease death or nonfatal myocardial infarction

Drug/Procedures Used:

Patients with stable angina were randomly assigned 20 mg nicorandil twice daily (n=2565) or placebo twice daily (n=2561) in addition to standard antianginal therapy and followed for a mean duration of 1.6 +/- 0.5 years. Analysis was by intention to treat.

Principal Findings:

The frequency of primary composite endpoint (coronary heart disease death, nonfatal myocardial infarction, or unplanned hospital admission for cardiac chest pain) was significantly lower in the nicorandil group than in the placebo group (15.5% versus 13.1%, hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.72–0.97; p=0.014). There was no significant difference in the secondary composite end-point event (coronary heart disease death or nonfatal myocardial infarction; 4.2% vs. 5.2%, HR 0.79, 95% CI 0.61–1.02; p=0.068). While all cause mortality was similar between nicorandil group and the placebo group (4.3% vs. 5.0%, HR 0.85, 95% CI 0.66-1.10; p=0.222), the rate of acute cornary syndromes (6.1% vs 7.6%, HR 0.79, 95% CI 0.64–0.98; p=0.028), and the rates for all cardiovascular events (14.7% vs. 17.4%, HR 0.86, 95% CI 0.75–0.98; p=0.027) favored nicoranil.

Interpretation:

Among patients with stable angina, antianginal therapy with nicorandil results in significant improvement in outcome due to a reduction in the composite endpoint of death, non-fatal myocardial infarction or unplanned admission for cardiac chest pain. Nicorandil is a nicotinamide ester that opens potassium/ATP channels and its administration is associated with a decrease in both pre-load and after load, and an improvement in coronary blood flow. In addition, it has a cardioprotective effect due to its ability to mimic ischemic preconditioning phenomena as a result of opening potassium ATP channels. Although this trial supports the beneficial effect of nicorandil in reducing coronary events in patients with stable angina, beta-blockers were utilized only in about 57% of these patients and no information was provided regarding the frequency of revascularization in the two groups of patients. More information and analysis from this study is required before the use of nicorandil can be broadly recommended in patients with stable angina who are being treated with standard anti-anginal therapy.

References:

The IONA Study Group: Effect of Nicorandil on Coronary Events in Patients with Stable Angina: The Impact of Nicorandil in Angina (IONA) Randomised Trial. Lancet 2002;359:1269-75.

Clinical Topics: Prevention, Stable Ischemic Heart Disease, Hypertension, Chronic Angina

Keywords: Myocardial Infarction, Potassium, Angina, Stable, Nicorandil, Confidence Intervals, Hypertension, Ischemic Preconditioning, Calcium Channel Blockers, Vasodilator Agents


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