Japan Working Groups of Acute Myocardial Infarction for the Reduction of Necrotic Damage by Atrial Natriuretic Peptide or Nicorandil - J-WIND – Presented at AHA 2006

Description:

The goal of these two trials was to evaluate the effect of the human atrial natriuretic peptide (hANP) carperitide and nicorandil, compared with control, among patients with ST elevation myocardial infarction (MI) treated with percutaneous coronary intervention (PCI).

Study Design

Study Design:

Patients Enrolled: 1,114
Mean Follow Up: Median follow-up, 2.6 years
Mean Patient Age: Mean age, 63 years
Female: 18

Patient Populations:

Age 20-79 years with first acute MI to be treated with PCI, chest pain lasting >30 minutes, and hospital admission within 12 hours of symptom onset

Exclusions:

Left main disease

Primary Endpoints:

1) Infarct size estimated by area under the curve of CK, and 2) LVEF

Secondary Endpoints:

All-cause mortality; cardiovascular events, including cardiac death, acute coronary syndrome, heart failure, and revascularization; and incidence of reperfusion injury, defined as malignant ventricular arrhythmia, recurrent ST elevation MI, or worsening chest pain

Drug/Procedures Used:

The J-WIND studies were comprised of two individual trials. In one trial, patients were randomized in a double-blind manner to hANP carperitide (0.025 µg/kg/min for 3 days; n = 277) or 5% glucose control (n = 292). In the other trial, patients were randomized in a double-blind manner to nicorandil (0.067 mg/kg bolus plus 1.67 µg/kg/min for 24 hours; n = 276) or saline control (n = 269). The trials were conducted in 65 hospitals in Japan.

Principal Findings:

At study entry, diabetes was present in 35% of patients and hyperlipidemia in 50%. Two-thirds of patients were current smokers. Infarct artery was the left anterior descending in 51% of patients.

The primary endpoint of infarct size as assessed by area under the curve of creatine kinase (CK) was 14.7% lower with carperitide compared with control (p = 0.016), but there was no difference between nicorandil and control (p = NS). Likewise, the co-primary endpoint of left ventricular ejection fraction (LVEF) was increased 5.1% with carperitide compared with control, but there was no difference between nicorandil and control (p = NS). Results were consistent in key subgroups. Among the secondary endpoints, reperfusion injury was reduced 25.9% with carperitide compared with control, but did not differ between nicorandil and control. There was no difference in mortality or the composite clinical endpoint between active treatment and control in either trial. The composite of cardiac death or heart failure was lower with carperitide than control (hazard ratio [HR] 0.27, p = 0.011), but did not differ for nicorandil versus control (HR 0.78, p = 0.60).

Interpretation:

Among patients with ST elevation MI treated with PCI, treatment with the hANP carperitide was associated with reductions in infarct size and increases in LVEF compared with control. Treatment with nicorandil was not associated with differences in infarct size or LVEF compared with control.

Also noteworthy was the more than 70% reduction in cardiac death or heart failure with the hANP carperitide over control. However, it should be noted that the present trial was small and larger trials would be needed to verify these findings for clinical events. No benefit was observed in any of the reported endpoints for nicorandil, a nicotinamide nitrate that activates potassium channels.

References:

Presented by Dr. Masafumi Kitakaze at the American Heart Association Annual Scientific Sessions, Chicago, IL, November 2006.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, EP Basic Science, Lipid Metabolism, Acute Heart Failure, Interventions and Vascular Medicine

Keywords: Myocardial Infarction, Potassium Channels, Creatine Kinase, Hyperlipidemias, Nicorandil, Percutaneous Coronary Intervention, Glucose, Reperfusion Injury, Chest Pain, Heart Failure, Stroke Volume, Atrial Natriuretic Factor, Diabetes Mellitus


< Back to Listings