title: Efficacy of medical therapy for the reduction of heart failure events in patients with implanted cardioverter defibrillators.
abstract: BACKGROUND
  Prophylactic therapy with the implantable cardioverter defibrillator (ICD) reduces the mortality among patients with left ventricular dysfunction; however, life-prolonging device therapy has been shown to be associated with an increased risk for subsequent heart failure (HF) events. There are limited data on the effect of the primary types of HF medications, angiotensin converting enzyme inhibitors (ACE-I), and beta-blockers on HF progression in ICD-treated patients.
  
  
  METHODS
  Multivariate Cox proportional hazards regression analysis was used to assess the effect of time-dependent medical therapy with ACE-I and beta-blockers on the development of HF in patients with an ICD in the Multicenter Automatic Defibrillator Trail (MADIT) II.
  
  
  RESULTS
  In multivariate analysis, ICD therapy was associated with a significant 39% increase in the risk of HF as compared with conventional medical therapy. ACE-I and beta-blockers exhibited a graded efficacy for the reduction in the risk of HF events in ICD-treated patients: the greatest risk reduction of HF was seen in patients taking combination therapy (HR = 0.36, P < 0.001), followed by patients using beta-blockers only (HR = 0.51, P = 0.017) and ACE-I only (HR = 0.64, P = 0.071). Beta-blocker subtypes (metoprolol [HR = 0.49, P = 0.001] and carvedilol [HR = 0.58, P = 0.004]) exhibited similar efficacy. Consistent results were demonstrated when the combined endpoint of HF or death was assessed.
  
  
  CONCLUSIONS
  ICD-treated patients experience an increased risk for HF events that can be significantly attenuated by medical therapy with beta-blockers and ACE-inhibitors.
authors.affiliation: Heart Research Follow-up Program, Cardiology Division, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Pietrasik
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Bronislava
authors.initials: B
authors.lastname: Polonsky
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D017147:Defibrillators, Implantable; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000209:etiology / Q000401:mortality / Q000628:therapy*
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors