Masafumi Kitakaze, MD, PhD, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, presented the results of the Japanese Working Groups of Acute Myocardial Infarction for the Reduction of Necrotic Damage by Atrial Natriuretic Peptide (ANP) or Nicorandil (J-WIND) trials conducted in Japan from 2001–2006. Carperitide, human recombinant ANP, is approved for the treatment of acute heart failure in Japan. Nicorandil, a nicotinamide nitrate that activates potassium channels in the heart, is used to treat chronic angina. These randomized, double-blind studies evaluated intervention with either carperitide or nicorandil on infarct size, left ventricular function, and associated outcomes.

The study population was patients experiencing their first heart attack. In one trial, patients were given either carperitide (0.025 mcg/kg/min for 3 days) or a 5% glucose solution as a placebo. In the second trial, patients were administered nicorandil (0.067 mg/kg bolus plus 1.67 mcg/kg/min for 24 hours) or a placebo saline infusion. The size of the infarct was determined by measuring the area under the curve (AUC) of creatinine kinase (CK). Chronic left ventricular function (LVEF) was evaluated via ventriculography.

There were no significant differences in demographics of the groups of patients in either trial. The carperitide trial randomized 569 patients, 277 to active treatment and 292 to placebo. Patients were followed for an average of 2.7 years. The CK AUC was 14.7% lower in patients treated with carperitide (p=0.016), and chronic LVEF was 5.1% higher than the control group (p=0.024). The incidence of a reperfusion injury was markedly reduced in the carperitide group (25.9% reduction; p=0.019). In terms of outcomes, carpertide-treated patients had a 73.3% reduction in risk of cardiac death or re-hospitalization for heart failure (HR=0.267; 95% CI [0.089–0.800]; p=0.011).

The nicorandil study randomized 545 patients, 276 to nicorandil and 269 to placebo. Patients were followed for an average of 2.5 years. Nicorandil did not demonstrate an effect on CK AUC, LVEF, or reperfusion injury, although it had a modest decrease in cardiac death and heart failure outcomes (HR=0.779; 95% CI [0.307–1.973]; p=0.597). Nicorandil oral therapy fared better. A subsequent analysis of nicorandil oral administration the chronic phase had positive effects on LVEF (p=0.034) and inhibited new lesions in non-culprit coronary arteries (p=0.010).

“These results will change the strategy of the acute phase treatment of heart attack”, predicted Dr. Kitakaze. Larger prospective randomized trials are needed to confirm these promising results.