CardioExchange Archive

Acute use of the popular macrolide antibiotic clarithromycin has been linked to a small but significant increase in cardiac death. In a report in the BMJ, researchers in Denmark analyzed the effects over a 14-year period of the acute use of penicillin V, roxithromycin, and clarithromycin.

Earlier research raised concerns that marcrolide antibiotics in general, and erythromycin and azithromycin in particular, might prolong the QT interval and increase the risk for fatal arrhythmias.

In the new study, clarithromycin was associated with a significant increase in the rate of sudden cardiac death compared with the other two antibiotics: 5.3 per 1000 person years for clarithromycin versus 2.5 per 1000 person-years for penicillin V and roxithromycin. After adjustment for baseline differences, the result remained significant (rate ratio, 1.76, CI  1.08-2.85). The authors calculated that compared with penicillin V, clarithromycin resulted in an absolute risk difference of 37 cardiac deaths per million courses of clarithromycin (CI 4-90). It should be noted, however, that the absolute number of events was quite low: in total there were 285 cardiac deaths that occurred during ongoing use of the study drugs, 18 of which occurred during use of clarithromycin.

The study raised the possibility that the increased risk was stronger in women than in men. “This finding is consistent with female sex being a known risk factor for drug induced cardiac arrhythmia in general and macrolide induced arrhythmia in particular,” the authors wrote.

The authors discussed the practical implications, if any, of their research:

On the one hand, the absolute risk is small, so this finding should probably have limited, if any, effect on prescribing practice in individual patients (with the possible exception of patients who have strong risk factors for drug induced arrhythmia). On the other hand, clarithromycin is one of the more commonly used antibiotics in many countries and many millions of people are prescribed this drug each year; thus, the total number of excess (potentially avoidable) cardiac deaths may not be negligible. These factors need to be considered when assessing the overall benefit/risk profile of macrolides (clarithromycin specifically)…