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Cardiovascular outcomes associated with use of clarithromycin: population based study

BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.h6926 (Published 14 January 2016) Cite this as: BMJ 2016;352:h6926

Re: Cardiovascular outcomes associated with use of clarithromycin: population based study

Dr. Blake helpfully reminds readers that in one of their investigations, Wong and colleagues1 used an H.pylori eradication regimen consisting of three products as their exposure of interest. We are not aware of evidence indicating that the initiation of such treatment commonly precedes myocardial infarction (and indeed the authors posit exactly the opposite). Despite this, there nevertheless remains the concern that rather than examining an exposure to clarithromycin alone, the authors are effectively examining the effects of exposure to the entire H. Pylori eradication regimen which also included a proton pump inhibitor and amoxicillin/metronidazole.

Interestingly, at least two observational studies posit an association between proton pump inhibitors and myocardial infarction.2,3 In addition, Wong et al.’s choice of control for the cohort study raises concerns regarding confounding by indication, although it is not clear that the use of doxycycline as an alternative would obviate such concerns given than many indications for clarithromycin and doxycycline do not overlap.

We believe the totality of published evidence supports an association between clarithromycin and rare but potentially serious cardiovascular events – whether these are sufficient to warrant dialogue in any particular encounter is for an individual clinician and patient to decide.

References
1. Wong AYS, Root A, Douglas IJ, et al. Cardiovascular outcomes associated with use of clarithromycin: population based study. BMJ. 2016;352:h6926.
2. Shah NH, LePendu P, Bauer-Mehren A, et al. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PloS ONE. 2015;10(6):e0124653. doi:10.1371/journal.pone.0124653.
3. Shih CJ, Chen YT, Ou SM, et al. Proton pump inhibitor use represents an independent risk factor for myocardial infarction. International Journal of Cardiology. 2014;177:292-7.

Competing interests: No competing interests

04 February 2016
Geetha Iyer
Student
G Caleb Alexander, Associate Professor, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health
Baltimore, MD, USA