title: Intravenous nicorandil for treatment of the urgent phase acute heart failure syndromes: A randomized, controlled trial.
abstract: BACKGROUND
  Vasodilators, such as nitroglycerin, have long been first-line treatments for acute heart failure syndromes (AHFS). Nicorandil is a vasodilator with dual potassium channel opening and nitrate properties. However, there are no randomized controlled studies of intravenous nicorandil safety and efficacy in the urgent phase AHFS. We examined the symptomatic, hemodynamic, and echocardiographic effects and safety, and 60-day clinical outcomes of intravenous nicorandil, in addition to standard therapy, in patients with AHFS in the urgent phase.
  
  
  METHODS
  In this prospective, randomized controlled trial, 106 AHFS patients were randomized within one hour of arrival to receive either standard therapy (control group, n=56) or standard therapy plus simultaneous intravenous nicorandil (0.2 mg/kg bolus followed by 0.2 mg/kg/h for 24 h; nicorandil group, n=50). Outcomes were assessed at 60 days.
  
  
  RESULTS
  Patients in the nicorandil group exhibited greater improvement of dyspnea as measured by change in a five-point Likert scale compared to those in the control group (after 1 h infusion: p=0.006, 6 h; p<0.001). The nicorandil group also showed significantly improved E/e', an estimate of left ventricular filling pressure, at 1 and 24 h ( p=0.001 and p=0.004, respectively). In addition, intravenous nicorandil therapy was safe and did not cause side effects such as excessive hypotension or reflex tachycardia. However, it did not reduce all-cause mortality and readmission rates at 60 days.
  
  
  CONCLUSIONS
  Addition of intravenous nicorandil to standard therapy for urgent phase AHFS improved dyspnea and left ventricular diastolic function but not 60-day outcome.
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Harada
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shigekiyo
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Naho
authors.initials: N
authors.lastname: Terada
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Okada
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawata
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Iima
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Fujisawa
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Kageyama
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Cardiovascular Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujinaga
mesh_terms: D061605:Administration, Intravenous / Q000379:methods*; D000368:Aged; D000369:Aged, 80 and over; D003971:Diastole / Q000187:drug effects; D004417:Dyspnea / Q000188:drug therapy; D004452:Echocardiography / Q000187:drug effects / Q000295:instrumentation; D004636:Emergency Service, Hospital; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020108:Nicorandil / Q000008:administration & dosage* / Q000494:pharmacology; D005996:Nitroglycerin / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D014665:Vasodilator Agents; D020108:Nicorandil; D005996:Nitroglycerin
keywords: Acute heart failure syndromes; dyspnea; echocardiography; nicorandil