title: Tolerability of beta-blocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF).
abstract: BACKGROUND
  beta-Blockade improves survival when administered over a long period of time to patients with heart failure. However, the time course of any possible deterioration during the titration phase has not been reported.
  
  
  RESULTS
  We looked at evidence of clinical deterioration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) by analyzing events and symptoms during the first 90 days. During titration, the Kaplan-Meier curves for the combined end point of all-cause mortality/all-cause hospitalization were similar in all patients randomized, with no significant difference in favor of placebo at any visit or in any of the analyzed subgroups (New York Heart Association class II, III/IV, or III/IV with ejection fraction <0.25, heart rate less-than-or-equal 76 bpm, and systolic blood pressure less-than-or-equal 120 mm Hg). The curves started to diverge in favor of beta-blockade after 60 days. Low heart rate was the main factor that limited titration. In New York Heart Association class III/IV, 5.9% of the patients receiving placebo discontinued study medicine during the first 90 days compared with 8.1% of those receiving metoprolol CR/XL (P=0.037 unadjusted, P=NS adjusted); corresponding figures in those with New York Heart Association class III/IV and ejection fraction <0.25 were 7.1% and 8.0% (P=NS). From day 90 until the end of the study, more patients in the placebo group discontinued study medicine in all subgroups. There was no change in diuretic or ACE inhibitor dosing with beta-blocker titration. Most patients reported no change in symptoms of breathlessness or fatigue during the titration phase.
  
  
  CONCLUSIONS
  When carefully titrated, metoprolol CR/XL can be given safely to the overwhelming majority of patients with stable mild to moderate heart failure, with minimal side effects or deterioration.
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD 21201, USA. sgottlie@medicine.umaryland.edu
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Gottlieb
authors.forename: Michael L
authors.initials: ML
authors.lastname: Fisher
authors.forename: John
authors.initials: J
authors.lastname: Kjekshus
authors.forename: Prakash
authors.initials: P
authors.lastname: Deedwania
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Jiri
authors.initials: J
authors.lastname: Vitovec
authors.forename: John
authors.initials: J
authors.lastname: Wikstrand
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008875:Middle Aged; D010349:Patient Compliance / Q000706:statistics & numerical data; D010352:Patient Dropouts / Q000706:statistics & numerical data; D012119:Respiration / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D003692:Delayed-Action Preparations; D004232:Diuretics; D008790:Metoprolol