The issue of clarithromycin and increased cardiac deaths

Just this last week I was discussing with my students, the various factors contributing to variable drug response, and possible differences in the risk-benefit ratios for the same drug in different individuals. The recent publicity about increased cardiac death risks associated with clarithromycin provides a useful case study for many of these issues. Follow these posts for a discussion about this interesting issue.

The original publication about this can be found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138354/

Essentially, this Danish study looked at a large sample (n=160,297) of patients treated with a 7-day course of clarithromycin. The control groups were patients who been treated with roxithromycin and penicillin V. They found an excess of 37 deaths per million doses of clarithromycin compared to penicillinV. This is a very small though statistically significant increase in risk. The risk appeared to be contributed largely by an increased risk primarily among women. No increased risk was observed for roxithromycin.

As in many epidemiological studies of this sort, the design is far from perfect and there are always ways to cast doubt on the significance of the findings. It is not necessary for this discussion to arbitrate on this matter. Rather, this report serve as a context for us to consider the various mechanisms that may contribute to inter-individual variability in the risk-benefit ratio for a drug such as clarithromycin.

(To be continued)