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AHA: Human Atrial Natiuretic Peptide May Reduce Reperfusion Injury


CHICAGO -- Stenting for an acute myocardial infarction has a better outcome when the reperfusion is followed up with an infusion of carperitide, a human atrial natriuretic peptide, Japanese researchers reported here.

CHICAGO, Nov. 15 -- Stenting for an acute myocardial infarction has a better outcome when the reperfusion is followed up with an infusion of carperitide, a human atrial natriuretic peptide, researchers reported here.

Infusion of the investigational compound reduced infarct size by 14.7% (P=0.016) and increased left ventricular ejection fraction by 5.1% (P=0.024) compared with placebo, said Masafumi Kitakaze, M.D., Ph.D., of the National Cardiovascular Center in Suita, Japan.

Carperitide also reduced reperfusion injury by 25.9% compared with placebo (P=0.019), said Dr. Kitakaze, reporting the results of the 65-center J-WIND trial (Japan-Working Groups of Acute Myocardial Infarction for the Reduction of Necrotic Damage by ANP or Nicorandil) at a late-breaking clinical trials session at the American Heart Association meeting.

In a sub-analysis that extrapolated the risk of heart failure and death based on change in ejection fraction and infarct size, caperitide was associated with an HR of 0.267 for either event (95% CI, 0.0l89-0.800, P=0.011).

He said the increase in ejection fraction was enough to move patients from heart failure-meaning an EF less than 40%--to above that threshold.

By contrast a competing strategy using nicorandil, a nicotinamide nitrate that activates potassium channels, did not reduce infarct size or reduce reperfusion injury.

The J-WIND trial was actually two parallel trials of different strategies to reduce infarct size, improve ejection fraction, and reduce revascularization injury.

In the caperitide study, 277 patients who underwent percutaneous coronary intervention for treatment of a first MI were randomized to caperitide infusion at the rate of 0.025 mg/kg/min for three days and 292 patients to 5% glucose infusion.

The competing strategy randomized 276 patients to nicorandil (0.067 mg/kg/bolus + 1.67 mg/kg/min for 24 hours) and 269 patients to saline infusion.

Patients were treated from December 2001 to August 2006 at 65 participating hospitals in Japan.

About 40% of the patients in the nicorandil arm were continued on oral nicorandil and those patients did have improved ventricular function and a reduction of new lesions in non-culprit arteries, he said.

Timothy Gardner, M.D., a cardiothoracic surgeon at the Christiana Care Health Services in Wilmington, Del., who was AHA program chair, said the results were interesting, but he noted that "these are early results from a trial that used very soft endpoints."

He said that measurement of left-ventricular ejection fraction by echocardiography is "a somewhat imprecise marker that varies according to operator."

Robert Harrington, M.D., of Duke in Durham, N.C. agreed that the results should be viewed cautiously.

Dr. Harrington, who served as discussant for the J-WIND trial, noted that about a dozen drugs that were tested for reduction of infarct size and reperfusion injury "all reported early, positive results."

Yet, none of those results was confirmed in larger trials, he said.

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