title: Additive beneficial effects of beta-blockers to angiotensin-converting enzyme inhibitors in the Survival and Ventricular Enlargement (SAVE) Study. SAVE Investigators.
abstract: OBJECTIVE
  This study assessed whether treatment with a beta-adrenergic blocking agent in addition to the use of the angiotensin-converting enzyme (ACE) inhibitor captopril decreases cardiovascular mortality and morbidity in patients with asymptomatic left ventricular dysfunction after myocardial infarction (MI) and whether the presence of neurohumoral activation at the time of hospital discharge predicts the effects of beta-blocker treatment in these patients.
  
  
  BACKGROUND
  Both beta-blockers and ACE inhibitors have been shown to have beneficial effects in patients with left ventricular dysfunction but no overt heart failure after MI. These patients often have persistent neurohumoral activation at the time of hospital discharge, and one would expect that patients with activation of the sympathetic nervous system derive the most benefit from treatment with beta-blockers. However, beta-blockers are underutilized in this high risk group of patients, and it is unknown whether their beneficial effects are additive to those of ACE inhibitors.
  
  
  METHODS
  We performed a retrospective analysis of data from the Survival and Ventricular Enlargement (SAVE) study and its neurohumoral substudy. The relations between beta-blocker use at the time of randomization and neurohumoral activation and the subsequent development of cardiovascular events were analyzed by use of Cox proportional hazards models controlling for covariates.
  
  
  RESULTS
  After adjustment for baseline imbalances, beta-blocker use was associated with a significant reduction in risk of cardiovascular death (30%, 95% confidence interval [CI] 12% to 44%) and development of heart failure (21%, 95% CI 3% to 36%), but the reduction in recurrent MI (11%, 95% CI 13% to 31%) was not significant. These reductions were independent of the use of captopril. Beta-blockers were not found to have a greater effect in patients with neurohumoral activation at the time of hospital discharge.
  
  
  CONCLUSIONS
  The beneficial effects of beta-blocker use at the time of hospital discharge in patients with asymptomatic left ventricular dysfunction after MI appear to be additive to those of captopril and other interventions known to improve prognosis. Neurohumoral activation at the time of hospital discharge fails to identify those patients who will derive the greatest benefit from treatment with beta-blockers.
authors.affiliation: Department of Medicine, Montreal Heart Institute, Quebec, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Vantrimpont
authors.forename: J L
authors.initials: JL
authors.lastname: Rouleau
authors.forename: C C
authors.initials: CC
authors.lastname: Wun
authors.forename: A
authors.initials: A
authors.lastname: Ciampi
authors.forename: M
authors.initials: M
authors.lastname: Klein
authors.forename: B
authors.initials: B
authors.lastname: Sussex
authors.forename: J M
authors.initials: JM
authors.lastname: Arnold
authors.forename: L
authors.initials: L
authors.lastname: Moyé
authors.forename: M
authors.initials: M
authors.lastname: Pfeffer
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D018377:Neurotransmitter Agents; D002216:Captopril