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antibiotics and risk of cardiac deaths

A paper in the British Medical Journal reported an association between use of the antibiotic clarithromycin and a small increased risk of cardiac deaths. The authors suggest that more research should be carried out before changing prescription practices. Roundup comments accompanied this before the headlines analysis.


Title, Date of Publication & Journal

Use of clarithromycin and roxithromycin and risk of cardiac death: cohort study

August 19th 2014

British Medical Journal


Claim supported by evidence?

Clarithromycin is a common antibiotic, used in a range of similar settings to penicillin. This paper identifies an apparent small but significant increase in the risk of cardiac death in a historical cohort study of Danish adults (40—74 years). There is no suggestion that current prescribing practice should change other than perhaps among those at high risk.



  • This is a well organised and implemented study of historical data (1997-2011) specifically chosen (age and previous medical history) to help identify any difference in cardiac death rate.
  • Evidence was found for an increased risk of cardiac death associated with the use of clarithromycin but not roxithromycin.
  • Comparison to penicillin (which is used to treat similar conditions as both clarithromycin and roxithromycin) as the reference group helps to reduce the potential for systematic differences between the groups with respect to underlying cardiac risk.
  • This paper is mainly of interest and importance to the medical research community, as it points to the need for further research, rather than being of public interest, since no changes in prescribing are currently recommending.


Study Conclusions

This study supports previous research indicating an increased risk of cardiac death for this class of drug (the absolute risk difference is 37 cardiac deaths per 1 million courses for clarithromycin compared to penicillin; equivalent 95% confidence interval is 4 to 90), as evidenced by QT prolongation.

The authors highlighted the weaknesses of their study and are suitably cautious in their conclusions, emphasising the need for further research to confirm these findings.



Detecting potential differences in low risk requires large studies such as this. Even then there is potential for such findings to be due to unidentified cofounders. For an excellent summary of strengths and limitations read this section of the paper. In brief:


  • This is a large study with nationwide coverage.
  • The authors have taken various measures to take account of potential confounding: (a) they excluded people with serious disease, who may have already been at higher risk of death; (b) the comparison group was those taking penicillin, making the groups more similar with respect to health status; and (c) they adjusted for a range of potential confounders by using a propensity score.



  • Despite the measures taken to adjust for confounding factors, residual confounding (confounding that has not been taken into account) cannot be ruled out since data on some factors that are related to cardiac death such as smoking status and BMI were not available. However, it is important to note that this could have lead to either an overestimate or an underestimate of the association between clarithromycin and cardiac mortality.


Before The Headlines is a service provided to the SMC by volunteer statisticians: members of the Royal Statistical Society (RSS), Statisticians in the Pharmaceutical Industry (PSI) and experienced statisticians in academia and research.  A list of contributors, including affiliations, is available here.

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