title: Cardiovascular outcomes associated with use of clarithromycin: population based study.
abstract: OBJECTIVE
  What is the association between clarithromycin use and cardiovascular outcomes?
  
  
  METHODS
  In this population based study the authors compared cardiovascular outcomes in adults aged 18 or more receiving oral clarithromycin or amoxicillin during 2005-09 in Hong Kong. Based on age within five years, sex, and calendar year at use, each clarithromycin user was matched to one or two amoxicillin users. The cohort analysis included patients who received clarithromycin (n=108,988) or amoxicillin (n=217,793). The self controlled case series and case crossover analysis included those who received Helicobacter pylori eradication treatment containing clarithromycin. The primary outcome was myocardial infarction. Secondary outcomes were all cause, cardiac, or non-cardiac mortality, arrhythmia, and stroke.
  
  
  CONCLUSIONS
  The propensity score adjusted rate ratio of myocardial infarction 14 days after the start of antibiotic treatment was 3.66 (95% confidence interval 2.82 to 4.76) comparing clarithromycin use (132 events, rate 44.4 per 1000 person years) with amoxicillin use (149 events, 19.2 per 1000 person years), but no long term increased risk was observed. Similarly, rate ratios of secondary outcomes increased significantly only with current use of clarithromycin versus amoxicillin, except for stroke. In the self controlled case analysis, there was an association between current use of H pylori eradication treatment containing clarithromycin and cardiovascular events. The risk returned to baseline after treatment had ended. The case crossover analysis also showed an increased risk of cardiovascular events during current use of H pylori eradication treatment containing clarithromycin. The adjusted absolute risk difference for current use of clarithromycin versus amoxicillin was 1.90 excess myocardial infarction events (95% confidence interval 1.30 to 2.68) per 1000 patients.
  
  
  CONCLUSIONS
  Current use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia, and cardiac mortality short term but no association with long term cardiovascular risks among the Hong Kong population.
  
  
  BACKGROUND
  ID was funded by grants from the Medical Research Council for this project. LS was funded by a grant from the Wellcome Trust. The authors have no competing interests. No additional data are available.
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China i.wong@ucl.ac.uk.
authors.forename: Angel Y S
authors.initials: AY
authors.lastname: Wong
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Root
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Douglas
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Celine S L
authors.initials: CS
authors.lastname: Chui
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Chan
authors.affiliation: Department of Mathematics and Statistics, Open University, Milton Keynes, UK.
authors.forename: Yonas
authors.initials: Y
authors.lastname: Ghebremichael-Weldeselassie
authors.affiliation: Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Liam
authors.initials: L
authors.lastname: Smeeth
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China Research Department of Practice and Policy, UCL School of Pharmacy, London, UK i.wong@ucl.ac.uk.
authors.forename: Ian C K
authors.initials: IC
authors.lastname: Wong
mesh_terms: D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects*; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D057216:Propensity Score; D016032:Randomized Controlled Trials as Topic; D012141:Respiratory Tract Infections / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D000658:Amoxicillin; D017291:Clarithromycin