title: Outcomes of implantable cardioverter-defibrillator use in patients with comorbidities: results from a combined analysis of 4 randomized clinical trials.
abstract: OBJECTIVE
  The aim of this study was to determine if the benefit of implantable cardioverter-defibrillators (ICDs) is modulated by medical comorbidity.
  
  
  BACKGROUND
  Primary prevention ICDs improve survival in patients at risk for sudden cardiac death. Their benefit in patients with significant comorbid illness has not been demonstrated.
  
  
  METHODS
  Original, patient-level datasets from MADIT I (Multicenter Automatic Defibrillator Implantation Trial I), MADIT II, DEFINITE (Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation), and SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) were combined. Patients in the combined population (N = 3,348) were assessed with respect to the following comorbidities: smoking, pulmonary disease, diabetes, peripheral vascular disease, atrial fibrillation, ischemic heart disease, and chronic kidney disease. The primary outcome was overall mortality, using the hazard ratio (HR) of time to death for patients receiving an ICD versus no ICD by extent of medical comorbidity, and adjusted for age, sex, race, left ventricular ejection fraction, use of antiarrhythmic drugs, beta-blockers, and angiotensin-converting enzyme inhibitors.
  
  
  RESULTS
  Overall, 25% of patients (n = 830) had <2 comorbid conditions versus 75% (n = 2,518) with significant comorbidity (≥2). The unadjusted hazard of death for patients with an ICD versus no ICD was significantly lower, but this effect was less for patients with ≥2 comorbidities (unadjusted HR: 0.71; 95% confidence interval: 0.61 to 0.84) compared with those with <2 comorbidities (unadjusted HR: 0.59; 95% confidence interval: 0.40 to 0.87). After adjustment, the benefit of an ICD decreased with increasing number of comorbidities (p = 0.004).
  
  
  CONCLUSIONS
  Patients with extensive comorbid medical illnesses may experience less benefit from primary prevention ICDs than those with less comorbidity; implantation should be carefully considered in sick patients. Further study of ICDs in medically complex patients is warranted.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Steinberg
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Sana M
authors.initials: SM
authors.lastname: Al-Khatib
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Rex
authors.initials: R
authors.lastname: Edwards
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: JooYoon
authors.initials: J
authors.lastname: Han
authors.affiliation: Seattle Institute for Cardiac Research, Seattle, Washington; Division of Cardiology, University of Washington, Seattle, Washington.
authors.forename: Gust H
authors.initials: GH
authors.lastname: Bardy
authors.affiliation: Department of Medicine, Columbia University, New York, New York.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Bigger
authors.affiliation: Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Buxton
authors.affiliation: Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, Minnesota.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Irving Institute for Clinical and Translational Research, Columbia University, New York, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Steinman
authors.affiliation: Departments of Medicine and Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Alfred
authors.initials: A
authors.lastname: Hallstrom
authors.affiliation: I.R.C.C.S. Policlinico San Donato, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cappato
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Kadish
authors.affiliation: Division of Cardiology, University of Washington, Seattle, Washington.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kudenchuk
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Mark
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Lurdes Y T
authors.initials: LY
authors.lastname: Inoue
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina. Electronic address: gillian.sanders@duke.edu.
authors.forename: Gillian D
authors.initials: GD
authors.lastname: Sanders
mesh_terms: D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D017147:Defibrillators, Implantable; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011322:Primary Prevention; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D013318:Stroke Volume; D016896:Treatment Outcome
keywords: comorbid illness; implantable cardioverter-defibrillator; outcomes; randomized trials