title: Cardioverter defibrillator implantation without induction of ventricular fibrillation: a single-blind, non-inferiority, randomised controlled trial (SIMPLE).
abstract: BACKGROUND
  Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing.
  
  
  METHODS
  In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation [SIMPLE]), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide. Exclusion criteria included pregnancy, awaiting transplantation, particpation in another randomised trial, unavailability for follow-up, or if it was expected that the ICD would have to be implanted on the right-hand side of the chest. Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned (1:1) using a computer-generated sequence to have either defibrillation testing (testing group) or not (no-testing group). We used random block sizes to conceal treatment allocation from the patients, and randomisation was stratified by clinical centre. Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock (ie, a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation). The non-inferiority margin was a hazard ratio (HR) of 1·5 calculated from a proportional hazards model with no-testing versus testing as the only covariate; if the upper bound of the 95% CI was less than 1·5, we concluded that ICD insertion without testing was non-inferior to ICD with testing. We examined safety with two, 30 day, adverse event outcome clusters. The trial is registered with ClinicalTrials.gov, number NCT00800384.
  
  
  RESULTS
  Between Jan 13, 2009, and April 4, 2011, of 2500 eligible patients, 1253 were randomly assigned to defibrillation testing and 1247 to no-testing, and followed up for a mean of 3·1 years (SD 1·0). The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients (90 [7% per year]) in the no-testing group than patients who did receive it (104 [8% per year]; HR 0·86, 95% CI 0·65-1·14; pnon-inferiority <0·0001). The first safety composite outcome occurred in 69 (5·6%) of 1236 patients with no-testing and in 81 (6·5%) of 1242 patients with defibrillation testing, p=0·33. The second, pre-specified safety composite outcome, which included only events most likely to be directly caused by testing, occurred in 3·2% of patients with no-testing and in 4·5% with defibrillation testing, p=0·08. Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event (in 20 [2%] of 1236 patients in the no-testing group vs 28 [2%] of 1242 patients in the testing group, p=0·25).
  
  
  CONCLUSIONS
  Routine defibrillation testing at the time of ICD implantation is generally well tolerated, but does not improve shock efficacy or reduce arrhythmic death.
  
  
  BACKGROUND
  Boston Scientific and the Heart and Stroke Foundation (Ontario Provincial office).
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada. Electronic address: Jeff.Healey@phri.ca.
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Healey
authors.affiliation: JW Goethe University, Frankfurt, Germany.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.affiliation: Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Glikson
authors.affiliation: Klinikum Kassel, Kassel, Germany.
authors.forename: Jorg
authors.initials: J
authors.lastname: Neuzner
authors.affiliation: Centre Hospitalier Universitaire, Rennes, France.
authors.forename: Phillipe
authors.initials: P
authors.lastname: Mabo
authors.affiliation: Hospital de Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Vinolas
authors.affiliation: Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Kautzner
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, QC, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: O'Hara
authors.affiliation: Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Lieselot
authors.initials: L
authors.lastname: VanErven
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Gadler
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.affiliation: Boston Scientific, Minneapolis MN, USA, and Brussels, Belgium.
authors.forename: Ursula
authors.initials: U
authors.lastname: Appl
authors.affiliation: Boston Scientific, Minneapolis MN, USA, and Brussels, Belgium.
authors.forename: Jim
authors.initials: J
authors.lastname: Gilkerson
authors.affiliation: Boston Scientific, Minneapolis MN, USA, and Brussels, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Pochet
authors.affiliation: Boston Scientific, Minneapolis MN, USA, and Brussels, Belgium.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Stein
authors.affiliation: Semmelweis University, Heart and Vascular Centre, Budapest, Hungary.
authors.forename: Bela
authors.initials: B
authors.lastname: Merkely
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Chrolavicius
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Brandi
authors.initials: B
authors.lastname: Meeks
authors.affiliation: Gottsegen National Institute of Cardiology, Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Foldesi
authors.affiliation: Montreal Heart Institute, Montreal, QC, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thibault
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
mesh_terms: D001145:Arrhythmias, Cardiac / Q000401:mortality / Q000628:therapy*; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000379:methods* / Q000401:mortality; D005260:Female; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011183:Postoperative Complications / Q000209:etiology* / Q000401:mortality; D011379:Prognosis; D019919:Prosthesis Implantation / Q000379:methods* / Q000401:mortality; D018570:Risk Assessment; D016037:Single-Blind Method; D014693:Ventricular Fibrillation / Q000209:etiology