Human Atrial Natriuretic Peptide Given After Heart-Attack Reduces Infarct Size And Produces Better Outcomes
Professor Masafumi Kitakaze, National Cardiovascular Centre Suita, Osaka, Japan, and team carried out two randomized trials -the J-WIND studies. One study assessed the effect of ANP, while the other looked at the effect of nicroandil on infarct size and cardiovascular outcomes.
The ANP trial involved 277 acute heart-attack patients who were randomly selected to receive intravenous ANP at a dose of 0•025μg/ kg per min for three days, while 292 patients were randomly given the same dose of placebo.
The nicroandil trial involved 276 patients who were randomly selected to receive intravenous nicroandil (0•067 mg/kg as a bolus, followed by 1•67 μg/kg as a 24-hour continuous infusion), while 269 patients received the same dose of placebo. They were all followed up for 2.7 years (median) in the ANP trial and 2.5 years in the nicroandil trial.
The ANP Trial (compared to placebo patients)
-- Infarct size was reduced by approximately 15%
-- LVEF (left-ventricular ejection fraction) increased by 5% (average)
The Nicroandil trial (compared to placebo patients)
-- Nicroandil administration did not lower infarct size
-- Oral administration of nicroandil during follow-up increased LVEF between the chronic and acute phases
Authors' hypothesis regarding ANP results:
"The reduction of infarct size and the improvement of LVEF might decrease mechanical stress on the non-infarcted myocardium, which might decrease hypertrophy and dilation of the non-infarcted myocardium. Since cardiac hypertrophy and dilation cause diastolic and systolic heart failure, a reduction of infarct size and an increase of LVEF could mediate beneficial clinical outcomes. However, we need to do another large-scale clinical trial to target clinical outcomes such as cardiovascular death, because our primary aim here was to test the reduction of infarct size."
Conclusion of the authors
"Our finding that treatment with ANP in the acute phase reduced the incidence or readmission to hospital for chronic heart failure, could help to reduce the physical, medical, and economic burdens on people around the world," the writers conclude.
Accompanying Comment
"Use of ANP as a treatment for acute myocardial infarction needs further investigation in a double-blind study, to assess the dose-response association, to test the robustness of the findings, and to further evaluate the mechanism of action before exposing many patients to this treatment," Dr Richard Bogle and Dr Martin Wilkins, Imperial College London and Hammersmith Hospital, London, UK, wrote in an Accompanying Comment.
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Written by: Christian Nordqvist
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