title: Risk of mortality and heart failure exacerbations associated with inhaled beta-adrenoceptor agonists among patients with known left ventricular systolic dysfunction.
abstract: OBJECTIVE
  Recent studies suggest that myocardial beta(2)-adrenoceptors may be important in chronic heart failure. We sought to determine if use of selective beta(2)-agonists was associated with hospitalization for heart failure and all-cause mortality.
  
  
  METHODS
  We studied a cohort of patients with left ventricular systolic dysfunction (LVSD). The outcome was the first hospitalization with a primary diagnosis of chronic heart failure or death from any cause. The exposure was the average number of beta-agonist canisters filled per month in the 90 days prior to and 15 days after enrollment.
  
  
  RESULTS
  Among 1,529 subjects, the relative risk (RR) of chronic heart failure hospital admission associated with inhaled beta-agonists followed a dose-response relationship: RR for one canister per month, 1.4 (95% confidence interval [CI], 0.9 to 2.0), RR for two canisters per month, 1.7 (95% CI, 1.2 to 2.5), and RR for three canisters per month, 2.1 (95% CI, 1.4 to 3.1). The RR of death demonstrated a similar finding: RR for one canister per month, 0.9 (95% CI, 0.5 to 1.5), RR for two canisters per month, 1.3 (95% CI, 0.9 to 2.1), and RR for three canisters per month, 2.0 (95% CI, 1.3 to 3.1). Adjusting for potential confounding factors did not affect the estimates.
  
  
  CONCLUSIONS
  Among subjects with LVSD, inhaled beta-agonists were associated with an increased risk of heart failure hospitalization, and all-cause mortality. Clinicians should carefully consider the etiology of dyspnea when prescribing beta-agonists to patients with LVSD.
authors.affiliation: Health Services Research and Development, Northwest Center of Excellence, VA Puget Sound Health Care System, Department of Veterans Affairs, Seattle, WA 98108, USA. dau@u.washington.edu
authors.forename: David H
authors.initials: DH
authors.lastname: Au
authors.forename: Edmunds M
authors.initials: EM
authors.lastname: Udris
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Fan
authors.forename: J Randall
authors.initials: JR
authors.lastname: Curtis
authors.forename: Mary B
authors.initials: MB
authors.lastname: McDonell
authors.forename: Stephan D
authors.initials: SD
authors.lastname: Fihn
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000368:Aged; D004417:Dyspnea / Q000139:chemically induced; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
chemical_list: D000318:Adrenergic beta-Agonists