Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation.
BACKGROUND
Early reperfusion therapy improves the clinical outcomes of patients with acute myocardial infarction (AMI), but benefits are limited by reperfusion injury in some patients. We examined the effect of nicorandil, a hybrid of K(ATP) channel opener and nicotinamide nitrate, on reactive oxygen species (ROS) formation and clinical outcomes after primary percutaneous coronary intervention (PCI) for AMI.


METHODS
Fifty-eight patients with AMI were randomized into control (n = 25) and nicorandil pretreatment groups (n = 33). In the nicorandil group, nicorandil (4 mg as a bolus injection followed by constant infusion at 8 mg/hour for 24 hours) was administered just after admission. ROS formation was assessed by measuring urinary excretion of 8-epi-prostaglandin F2alpha (PGF2alpha) and compared between the 2 groups. Cardiac function and the incidence of reperfusion injury and cardiac events were also compared.


RESULTS
Urinary 8-epi-PGF2alpha excretion was increased 2-fold at 60 to 90 minutes after PCI in the control group, whereas it was unchanged after PCI in the nicorandil group (P <.0001 between the 2 groups). The incidence of no-reflow phenomenon was lower in the nicorandil group than in the control group. Left ventricular ejection fraction and cardiac index at 6 months were greater in the nicorandil group than in controls. Plasma brain natriuretic peptide level at 6 months was lower in the nicorandil group. Incidences of inhospital cardiac events and rehospitalization were lower in the nicorandil group than in controls.


CONCLUSIONS
Nicorandil improves cardiac function and clinical outcomes in patients with AMI. Suppression of ROS formation may be involved in the mechanism.
Ono
Hirotsugu
H
The Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.
Osanai
Tomohiro
T
Ishizaka
Hiroshi
H
Hanada
Hiroyuki
H
Kamada
Takaatsu
T
Onodera
Hiroyuki
H
Fujita
Norio
N
Sasaki
Shingo
S
Matsunaga
Toshiro
T
Okumura
Ken
K
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D003131:Combined Modality Therapy; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D020108:Nicorandil / Q000494:pharmacology / Q000627:therapeutic use*; D011292:Premedication; D011669:Pulmonary Wedge Pressure; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013318:Stroke Volume; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects*
D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D020108:Nicorandil; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost