title: Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies.
abstract: OBJECTIVE
  To study the association of clarithromycin with cardiovascular events in the setting of acute exacerbations of chronic obstructive pulmonary disease and community acquired pneumonia.
  
  
  METHODS
  Analysis of two prospectively collected datasets.
  
  
  METHODS
  Chronic obstructive pulmonary disease dataset including patients admitted to one of 12 hospitals around the United Kingdom between 2009 and 2011; Edinburgh pneumonia study cohort including patients admitted to NHS Lothian Hospitals between 2005 and 2009.
  
  
  METHODS
  1343 patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease and 1631 patients admitted with community acquired pneumonia.
  
  
  METHODS
  Hazard ratios for cardiovascular events at one year (defined as hospital admissions with acute coronary syndrome, decompensated cardiac failure, serious arrhythmia, or sudden cardiac death) and admissions for acute coronary syndrome (acute ST elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina). Secondary outcomes were all cause and cardiovascular mortality at one year.
  
  
  RESULTS
  268 cardiovascular events occurred in the acute exacerbations of chronic obstructive pulmonary disease cohort and 171 in the community acquired pneumonia cohort over one year. After multivariable adjustment, clarithromycin use in acute exacerbations of chronic obstructive pulmonary disease was associated with an increased risk of cardiovascular events and acute coronary syndrome-hazard ratios 1.50 (95% confidence interval 1.13 to 1.97) and 1.67 (1.04 to 2.68). After multivariable adjustment, clarithromycin use in community acquired pneumonia was associated with increased risk of cardiovascular events (hazard ratio 1.68, 1.18 to 2.38) but not acute coronary syndrome (1.65, 0.97 to 2.80). The association between clarithromycin use and cardiovascular events persisted after matching for the propensity to receive clarithromycin. A significant association was found between clarithromycin use and cardiovascular mortality (adjusted hazard ratio 1.52, 1.02 to 2.26) but not all cause mortality (1.16, 0.90 to 1.51) in acute exacerbations of chronic obstructive pulmonary disease. No association was found between clarithromycin use in community acquired pneumonia and all cause mortality or cardiovascular mortality. Longer durations of clarithromycin use were associated with more cardiovascular events. Use of β lactam antibiotics or doxycycline was not associated with increased cardiovascular events in patients with acute exacerbations of chronic obstructive pulmonary disease, suggesting an effect specific to clarithromycin.
  
  
  CONCLUSIONS
  The use of clarithromycin in the setting of acute exacerbations of chronic obstructive pulmonary disease or community acquired pneumonia may be associated with increased cardiovascular events. These findings require confirmation in other datasets.
authors.affiliation: Ninewells Hospital, Dundee DD1 9SY, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Schembri
authors.forename: Peter A
authors.initials: PA
authors.lastname: Williamson
authors.forename: Philip M
authors.initials: PM
authors.lastname: Short
authors.forename: Aran
authors.initials: A
authors.lastname: Singanayagam
authors.forename: Ahsan
authors.initials: A
authors.lastname: Akram
authors.forename: Joanne
authors.initials: J
authors.lastname: Taylor
authors.forename: Anika
authors.initials: A
authors.lastname: Singanayagam
authors.forename: Adam T
authors.initials: AT
authors.lastname: Hill
authors.forename: James D
authors.initials: JD
authors.lastname: Chalmers
mesh_terms: D054058:Acute Coronary Syndrome / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology; D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000494:pharmacology; D017291:Clarithromycin / Q000009:adverse effects* / Q000494:pharmacology; D017714:Community-Acquired Infections / Q000188:drug therapy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D019983:Guideline Adherence; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000401:mortality / Q000503:physiopathology; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin