Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials.
BACKGROUND
Patients who have acute myocardial infarction remain at major risk of cardiovascular events. We aimed to assess the effects of either human atrial natriuretic peptide or nicorandil on infarct size and cardiovascular outcome.


METHODS
We enrolled 1216 patients who had acute myocardial infarction and were undergoing reperfusion treatment in two prospective, single-blind trials at 65 hospitals in Japan. We randomly assigned 277 patients to receive intravenous atrial natriuretic peptide (0.025 microg/kg per min for 3 days) and 292 the same dose of placebo. 276 patients were assigned to receive intravenous nicorandil (0.067 mg/kg as a bolus, followed by 1.67 microg/kg per min as a 24-h continuous infusion), and 269 the same dose of placebo. Median follow-up was 2.7 (IQR 1.5-3.6) years for patients in the atrial natriuretic peptide trial and 2.5 (1.5-3.7) years for those in the nicorandil trial. Primary endpoints were infarct size (estimated from creatine kinase) and left ventricular ejection fraction (gauged by angiography of the left ventricle).


RESULTS
43 patients withdrew consent after randomisation, and 59 did not have acute myocardial infarction. We did not assess infarct size in 50 patients for whom we had fewer than six samples of blood. We did not have angiographs of left ventricles in 383 patients. Total creatine kinase was 66,459.9 IU/mL per h in patients given atrial natriuretic peptide, compared with 77,878.9 IU/mL per h in controls, with a ratio of 0.85 between these groups (95% CI 0.75-0.97, p=0.016), which indicated a reduction of 14.7% in infarct size (95% CI 3.0-24.9%). The left ventricular ejection fraction at 6-12 months increased in the atrial natriuretic peptide group (ratio 1.05, 95% CI 1.01-1.10, p=0.024). Total activity of creatine kinase did not differ between patients given nicorandil (70 520.5 IU/mL per h) and controls (70 852.7 IU/mL per h) (ratio 0.995, 95% CI 0.878-1.138, p=0.94). Intravenous nicorandil did not affect the size of the left ventricular ejection fraction, although oral administration of nicorandil during follow-up increased the left ventricular ejection fraction between the chronic and acute phases. 29 patients in the atrial natriuretic peptide group had severe hypotension, compared with one in the corresponding placebo group.


CONCLUSIONS
Patients with acute myocardial infarction who were given atrial natriuretic peptide had lower infarct size, fewer reperfusion injuries, and better outcomes than controls. We believe that atrial natriuretic peptide could be a safe and effective adjunctive treatment in patients with acute myocardial infarction who receive percutaneous coronary intervention.
Kitakaze
Masafumi
M
Cardiovascular Division of Medicine, National Cardiovascular Centre, Suita, Osaka, Japan. kitakaze@hsp.ncvc.go.jp
Asakura
Masanori
M
Kim
Jiyoong
J
Shintani
Yasunori
Y
Asanuma
Hiroshi
H
Hamasaki
Toshimitsu
T
Seguchi
Osamu
O
Myoishi
Masafumi
M
Minamino
Tetsuo
T
Ohara
Takahiro
T
Nagai
Yoshiyuki
Y
Nanto
Shinsuke
S
Watanabe
Kouki
K
Fukuzawa
Shigeru
S
Hirayama
Atsushi
A
Nakamura
Natsuki
N
Kimura
Kazuo
K
Fujii
Kenshi
K
Ishihara
Masaharu
M
Saito
Yoshihiko
Y
Tomoike
Hitonobu
H
Kitamura
Soichiro
S
D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D020108:Nicorandil / Q000008:administration & dosage / Q000627:therapeutic use*; D015427:Reperfusion Injury; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D014665:Vasodilator Agents; D020108:Nicorandil; D009320:Atrial Natriuretic Factor; D003402:Creatine Kinase