title: Risk of non-fatal cardiac failure and ischaemic heart disease with long acting beta 2 agonists.
abstract: BACKGROUND
  The long term safety of beta agonists, particularly in patients with heart disease, has not been fully established.
  
  
  METHODS
  This study accessed the results of three cohort studies involving: 12,294 patients receiving at least one prescription for nedocromil between November 1986 and September 1988; 15,407 patients prescribed salmeterol between December 1990 and May 1991; and 8098 patients prescribed bambuterol between February 1993 and December 1995. Details of all dispensed prescriptions for these drugs prescribed by general practitioners in England soon after their launch were provided in confidence by the Prescription Pricing Authority. Questionnaires were sent to the prescriber asking for details of events occurring after the first prescription (prescription event monitoring). Rates and relative risks of non-fatal cardiac failure and ischaemic heart disease were calculated, comparing bambuterol and salmeterol with the reference drug nedocromil.
  
  
  RESULTS
  The age and sex adjusted relative risk of non-fatal cardiac failure associated with bambuterol was 3.41 (95% confidence limits (CL) 1.99 to 5.86) when compared with nedocromil. When salmeterol was compared with nedocromil the adjusted relative risk of non-fatal cardiac failure was 1.10 (95% CL 0.63 to 1.91). The adjusted relative risk of non-fatal ischaemic heart disease was 1.23 (95% CL 0.73 to 2.08) and 1.07 (95% CL 0.69 to 1.66) for bambuterol and salmeterol, compared with nedocromil, respectively. However, in the first month of exposure the adjusted relative risk of non-fatal ischaemic heart disease was 3.95 (95% CL 1.38 to 11.31) when bambuterol was compared with nedocromil.
  
  
  CONCLUSIONS
  Caution should be exercised when prescribing long acting oral beta agonists to patients at risk of cardiac failure. More definitive evidence would come from prospective randomised trials.
authors.affiliation: School of Medicine, Faculty of Medicine, Health and Biological Sciences, University of Southampton.
authors.forename: R M
authors.initials: RM
authors.lastname: Martin
authors.forename: N R
authors.initials: NR
authors.lastname: Dunn
authors.forename: S N
authors.initials: SN
authors.lastname: Freemantle
authors.forename: R D
authors.initials: RD
authors.lastname: Mann
mesh_terms: D000318:Adrenergic beta-Agonists / Q000009:adverse effects*; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives*; D018927:Anti-Asthmatic Agents / Q000009:adverse effects; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000139:chemically induced*; D017835:Nedocromil / Q000009:adverse effects; D012306:Risk; D000068299:Salmeterol Xinafoate; D013726:Terbutaline / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors
chemical_list: D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D017835:Nedocromil; D000068299:Salmeterol Xinafoate; D013726:Terbutaline; D000420:Albuterol; C047766:bambuterol