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Cardiovascular outcomes associated with use of clarithromycin: population based study

BMJ 2016; 352 doi: (Published 14 January 2016) Cite this as: BMJ 2016;352:h6926
  1. Angel Y S Wong, PhD student1,
  2. Adrian Root, academic general practitioner2,
  3. Ian J Douglas, senior lecturer2,
  4. Celine S L Chui, PhD student1,
  5. Esther W Chan, assistant professor1,
  6. Yonas Ghebremichael-Weldeselassie, research associate3,
  7. Chung-Wah Siu, associate professor4,
  8. Liam Smeeth, professor2,
  9. Ian C K Wong, professor1 5
  1. 1Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
  2. 2Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
  3. 3Department of Mathematics and Statistics, Open University, Milton Keynes, UK
  4. 4Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
  5. 5Research Department of Practice and Policy, UCL School of Pharmacy, London, UK
  1. Correspondence to: I C K Wong, Research Department of Practice and Policy, UCL School of Pharmacy, London WC1N 1AX, UK i.wong{at}
  • Accepted 13 November 2015


Study question 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.

Study answer and limitations 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.

What this study adds 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.

Funding, competing interests, data sharing 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.


  • We thank the Hong Kong Hospital Authority for access to data and Michael Mok and Martijn Schuemie for their advice and contribution to our study.

  • Contributors: AYSW, AR, ID, and ICKW conceived and designed the study. AYSW and AR had principal responsibility for data analysis, drafting and revising the manuscript, and final approval. All authors contributed to the analysis, were responsible for the interpretation of the data, and drafted, revised, and gave final approval of the manuscript. AYSW and AR are the guarantors.

  • Funding: During the conduct of the study, ID was funded by grants from the Medical Research Council for this project. LS was funded by a grant from the Wellcome Trust. The sponsors had no role in the study design; collection, analysis, and interpretation of the data; the writing of the article; or the decision to submit the manuscript for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the institutional review board of the University of Hong Kong/Hospital Authority Hong Kong west cluster (UW 14-032). Informed consent was not required for research based on routine data.

  • Data sharing: No additional data available.

  • Transparency: AYSW and AR affirm that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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