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Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f1235 (Published 22 March 2013) Cite this as: BMJ 2013;346:f1235
  1. Stuart Schembri, consultant respiratory physician1,
  2. Peter A Williamson, consultant respiratory physician2,
  3. Philip M Short, clinical lecturer in respiratory medicine13,
  4. Aran Singanayagam, clinical research fellow4,
  5. Ahsan Akram, clinical research fellow5,
  6. Joanne Taylor, foundation doctor5,
  7. Anika Singanayagam, clinical research fellow6,
  8. Adam T Hill, consultant respiratory physician5, honorary senior lecturer7,
  9. James D Chalmers, clinical lecturer in respiratory medicine13
  1. 1Ninewells Hospital, Dundee DD1 9SY, UK
  2. 2Perth Royal Infirmary, Perth PH1 1NX, UK
  3. 3University of Dundee, Dundee, UK
  4. 4Imperial College London, London SW7 2AZ, UK
  5. 5Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK
  6. 6Chase Farm and Barnet Hospitals NHS Trust, London E1 1BB, UK
  7. 7University of Edinburgh, Edinburgh, UK
  1. Correspondence to: J D Chalmers jameschalmers1{at}nhs.net
  • Accepted 8 February 2013

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.

Design Analysis of two prospectively collected datasets.

Setting 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.

Population 1343 patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease and 1631 patients admitted with community acquired pneumonia.

Main outcome measures 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.

Footnotes

  • We thank Ross Archibald, University of Dundee; Louise Peet, University of Dundee; Charly Sengheiser, Doncaster Royal Infirmary; Duneesha De Fonseka, Doncaster Royal Infirmary; Gillian B Fleming, Edinburgh Royal Infirmary; Hazel Rooney, Perth Royal Infirmary; Duncan Mills, Royal Infirmary of Edinburgh; Sarah Higgins, Doncaster Royal Infirmary; John Corcoran, John Radcliffe Hospital, Oxford; Joseph Hodgson, NHS Tayside; Martin K Smith, NHS Borders; and Mudher Al-Khairalla, Doncaster Royal Infirmary for their help with data collection.

  • Contributors: All authors were involved in the design of the study, analysis and interpretation of results, and preparation and revision of the manuscript. All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. JDC is the guarantor.

  • Funding: No specific funding.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; 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: Routine collection of clinical data was approved by local Caldicott guardians and the local research ethics committee, with the requirement for informed consent waived (reference number NR/0906AB1). Additional data collection was approved by the South East Scotland research ethics committee (reference numbers S1104/15 and S1103/27).

  • Data sharing: No additional data available.

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