title: Effect of metoprolol versus carvedilol on outcomes in MADIT-CRT (multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy).
abstract: OBJECTIVE
  This study sought to compare the effects of metoprolol and carvedilol in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study.
  
  
  BACKGROUND
  The impact of beta-blockers in heart failure (HF) patients with devices is uninvestigated.
  
  
  METHODS
  All patients receiving either metoprolol or carvedilol in the MADIT-CRT study were identified and compared. Time-dependent Cox proportional hazard regression analyses were performed to assess differences in hospitalization for HF or death and ventricular arrhythmias.
  
  
  RESULTS
  Hospitalization for HF or death occurred in 30% of the patients on metoprolol and in 23% on carvedilol. Treatment with carvedilol was associated with a significantly decreased risk of hospitalization for HF or death when compared with metoprolol (hazard ratio [HR]: 0.70, [95% confidence interval (CI): 0.57 to 0.87], p = 0.001). This reduction in risk was further attenuated in the subgroup of cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) patients (HR: 0.61 [95% CI: 0.46 to 0.82], p = 0.001) and CRT-D patients with left bundle branch block (LBBB) (HR: 0.51 [95% CI: 0.35 to 0.76], p < 0.001). Ventricular arrhythmias occurred in 26% and in 22%, respectively, of the patients receiving metoprolol or carvedilol (HR: 0.80 [95% CI: 0.63 to 1.00], p = 0.050). General use of beta-blockers and adherence in this study was high, and a clear dose-dependent relationship was found in carvedilol, but not in metoprolol.
  
  
  CONCLUSIONS
  In HF patients in New York Heart Association functional class I and II and with wide QRS complexes, carvedilol was associated with a 30% reduction in hospitalizations for HF or death when compared with metoprolol. A novel beneficial and synergistic effect of carvedilol was seen in patients with CRT-D and LBBB. Furthermore, we found a pronounced dose-dependent relationship in carvedilol, but not in metoprolol.
authors.affiliation: Heart Research Follow-up Program, Cardiology Division, University of Rochester Medical Center, Rochester, NY 14642, USA. mruwald@hotmail.com
authors.forename: Martin H
authors.initials: MH
authors.lastname: Ruwald
authors.forename: Anne-Christine H
authors.initials: AC
authors.lastname: Ruwald
authors.forename: Christian
authors.initials: C
authors.lastname: Jons
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Alexis
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D002227:Carbazoles / Q000008:administration & dosage*; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D000077261:Carvedilol; D003131:Combined Modality Therapy; D017147:Defibrillators, Implantable; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011412:Propanolamines / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013318:Stroke Volume; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol