title: Use of clarithromycin and roxithromycin and risk of cardiac death: cohort study.
abstract: OBJECTIVE
  To assess the risk of cardiac death associated with the use of clarithromycin and roxithromycin.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Denmark, 1997-2011.
  
  
  METHODS
  Danish adults, 40-74 years of age, who received seven day treatment courses with clarithromycin (n = 160,297), roxithromycin (n = 588,988), and penicillin V (n = 4,355,309).
  
  
  METHODS
  The main outcome was risk of cardiac death associated with clarithromycin and roxithromycin, compared with penicillin V. Subgroup analyses were conducted according to sex, age, risk score, and concomitant use of drugs that inhibit the cytochrome P450 3A enzyme, which metabolises macrolides.
  
  
  RESULTS
  A total of 285 cardiac deaths were observed. Compared with use of penicillin V (incidence rate 2.5 per 1000 person years), use of clarithromycin was associated with a significantly increased risk of cardiac death (5.3 per 1000 person years; adjusted rate ratio 1.76, 95% confidence interval 1.08 to 2.85) but use of roxithromycin was not (2.5 per 1000 person years; adjusted rate ratio 1.04, 0.72 to 1.51). The association with clarithromycin was most pronounced among women (adjusted rate ratios 2.83 (1.50 to 5.36) in women and 1.09 (0.51 to 2.35) in men). Compared with penicillin V, the adjusted absolute risk difference was 37 (95% confidence interval 4 to 90) cardiac deaths per 1 million courses with clarithromycin and 2 (-14 to 25) cardiac deaths per 1 million courses with roxithromycin.
  
  
  CONCLUSIONS
  This large cohort study found a significantly increased risk of cardiac death associated with clarithromycin. No increased risk was seen with roxithromycin. Given the widespread use of clarithromycin, these findings call for confirmation in independent populations.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen S, Denmark htr@ssi.dk.
authors.forename: Henrik
authors.initials: H
authors.lastname: Svanström
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen S, Denmark.
authors.forename: Björn
authors.initials: B
authors.lastname: Pasternak
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen S, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Hviid
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000401:mortality*; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D065692:Cytochrome P-450 CYP3A Inhibitors; D003718:Denmark / Q000453:epidemiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010404:Penicillin V / Q000008:administration & dosage / Q000009:adverse effects; D057216:Propensity Score; D012042:Registries; D015575:Roxithromycin / Q000008:administration & dosage / Q000009:adverse effects; D012737:Sex Factors
chemical_list: D000900:Anti-Bacterial Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D015575:Roxithromycin; D017291:Clarithromycin; D010404:Penicillin V