As noted previously in this blog (New FDA warning for azithromycin (Zithromax) | gutsandgrowth), there have been concerns raised about the risk of cardiovascular death due to the use of azithromycin. An editorial and new study indicate that this risk is mainly confined to patients at high cardiovascular risk (NEJM 2013; 1665-67 [editorial], 1704-12 [study]).
Background: in 2011, “approximately 40.3 million people in the United States (roughly one eighth of the population) received an outpatient prescription for the macrolide azithromycin.”
In an observational study published last year (NEJM 2012; 366: 1881-90), azithromycin resulted in one death for every 21,000 outpatient prescriptions in comparison to amoxicillin. Among those with high cardiovascular risk factors, this number was much higher: one in 4100; whereas in those with no risk factors, it was less than one per 100,000. The risks also corresponded to peak drug levels as the increase in events took place during the 5-day course and an increased risk was not evident subsequently.
The newest study, referenced above. used data from a Danish national health care registry (18-64 year olds). These patients had a lower cardiovascular risk profile. More than one million prescriptions were studied. They found no difference in cardiovascular deaths between azithromycin and penicillin. In a subgroup analysis of patients with a history of cardiovascular disease, the risk ratio was 1.35 though this did not reach statistical significance.
The editorial notes that azithromycin has been shown to reduce deaths in patients treated for community-acquired pneumonia. However, the two most common indications for treatment remain bronchitis and sinusitis.
Bottom-line: The risks of azithromycin in young and middle-aged persons is exceedingly low or nonexistent. In individuals with cardiovascular risk factors, azithromycin, other macrolides and fluoroquinolones could trigger a lethal arrhythmia.