title: Results of a curtailed randomized controlled trial, evaluating the efficacy and safety of azimilide in patients with implantable cardioverter-defibrillators: The SHIELD-2 trial.
abstract: BACKGROUND
  Frequent hospital attendances in patients with implantable cardioverter-defibrillators (ICDs) result in significant morbidity and health care costs. Current drugs to reduce ICD shocks and hospital visits have limited efficacy and considerable toxicity. We evaluated the efficacy and safety of azimilide, a novel oral class III antiarrhythmic, for use in ICD patients.
  
  
  METHODS
  A total of 240 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled trial to evaluate the effect of oral azimilide 75 mg daily in ICD patients with previously documented ventricular tachycardia or ventricular fibrillation, and a left ventricular ejection fraction ≤40%. The primary outcome metric was the adjudicated time-to-first unplanned cardiovascular (CV) hospitalization, or CV emergency department (ED) visit, or CV death. The trial was prematurely discontinued due to withdrawal of study sponsorship.
  
  
  RESULTS
  Azimilide demonstrated numerical but statistically nonsignificant reductions in the primary composite outcome (odds ratio [OR] 0.79, 95% CI 0.44-1.44), unplanned CV hospitalizations (OR 0.75, 95% CI 0.41-1.38), ED visits (OR 0.68, 95% CI 0.35-1.31), and all-cause shocks (OR 0.58, 95% CI 0.32-1.05). The incidence of adverse events was lower in the azimilide group. Neutropenia was not observed (absolute neutrophil count <1000 μ/L), and there was one possible torsade de pointes case that led to a successful ICD discharge.
  
  
  CONCLUSIONS
  The SHIELD-2 trial was statistically underpowered due to early trial termination and did not meet its primary objective. Despite this limitation, azimilide showed promise as a safe and effective drug in reducing all-cause shocks, unplanned hospitalizations, and ED visits in ICD patients.
authors.affiliation: Lankenau Medical Center and Lankenau Institute for Medical Research, Wynnewood, PA.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Robinson
authors.affiliation: Allergan plc. (Forest Laboratories), Jersey City, NJ.
authors.forename: David B
authors.initials: DB
authors.lastname: Bharucha
authors.affiliation: Stanford University School of Medicine, Stanford, CA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: University of Toronto and St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
authors.affiliation: Lankenau Medical Center and Lankenau Institute for Medical Research, Wynnewood, PA; Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA. Electronic address: koweyp@mlhs.org.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kowey
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D004554:Electric Countershock; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D006827:Hydantoins / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010879:Piperazines / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D013318:Stroke Volume; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000628:therapy*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000628:therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D010879:Piperazines; C086123:azimilide