title: Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial.
abstract: OBJECTIVE
  We studied the influence of heart rate (HR), systolic blood pressure (SBP), and beta-blocker dose on outcome in the 2599 out of 3029 patients in Carvedilol Or Metoprolol European Trial (COMET) who were alive and on study drug at 4 months after randomization (time of first visit on maintenance therapy).
  
  
  RESULTS
  By multivariable analysis, baseline HR, baseline SBP, and their change after 4 months were not independently related to subsequent outcome. In a multivariable analysis including clinical variables, HR above and SBP below the median value achieved at 4 months predicted subsequent increased mortality [relative risk (RR) for HR>68 b.p.m. 1.333; 95% confidence intervals (CI) 1.152-1.542; P<0.0001 and RR for SBP>120 mmHg 0.78; 95% CI 0.671-0.907; P<0.0013]. Achieving target beta-blocker dose was associated with a better outcome (RR 0.779; 95% CI 0.662-0.916; P<0.0025). The superiority of carvedilol as compared to metoprolol tartrate was maintained in a multivariable model (RR 0.767; 95% CI 0.663-0.887; P=0.0004) and there was no interaction with HR, SBP, or beta-blocker dose.
  
  
  CONCLUSIONS
  Beta-blocker dose, HR, and SBP achieved during beta-blocker therapy have independent prognostic value in heart failure. None of these factors influenced the beneficial effects of carvedilol when compared with metoprolol tartrate at the pre-defined target doses used in COMET.
authors.affiliation: Cattedra di Cardiologia, Università di Brescia, Italy. metramarco@libero.it
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Lenarda
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.forename: Willem J
authors.initials: WJ
authors.lastname: Remme
authors.forename: Beatrix
authors.initials: B
authors.lastname: Lutiger
authors.forename: Armin
authors.initials: A
authors.lastname: Scherhag
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Lukas
authors.forename: Andrew
authors.initials: A
authors.lastname: Charlesworth
authors.forename: Philip A
authors.initials: PA
authors.lastname: Poole-Wilson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D001794:Blood Pressure / Q000502:physiology*; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol