Should We Stop Prescribing Azithromycin?

In 2011, Azithromycin was the seventh most prescribed (55.3 million prescriptions) medication according to IMS Health. There have been several publications indicating that the use of macrolide antibiotics increase risk of serious ventricular arrhythmias and sudden cardiac death (FDA Adverse Event Reporting System). Specifically, two recent studies in NEJM were published looking at the risk of Azithromycin with cardiovascular death and received lots of press recently.

Azithromycin and the Risk of Cardiovascular Death

What They Did:

Retrospective, Observational Cohort Study
Tennessee Medicaid Cohort
Compared

1. No antibiotics (1,391,180 prescriptions)
2. Azithromycin (347,795 prescriptions)
3. Amoxicillin (1,348,672 prescriptions)

Detected an increased risk of death

Primary Outcomes:

Cardiovascular death
Death from any cause

Results:

Cardiovascular Risk Factors in This Study: Smoking, high BMI, poor diet, and low physical activity
NO statistically significant risk of death after the 5 day course of azithromycin completed

Limitation:

Observational, non-randomized clinical trial

Conclusion:

During 5 days of azithromycin therapy, there is a small absolute increase in cardiovascular deaths and most pronounced in patients with a high baseline risk of cardiovascular disease.

What They Did:

Retrospective, Observational Cohort Study
Danish Adults
Compared
- No antibiotics vs Azithromycin (1,102050 prescriptions compared in 1:1 ratio)
- Azithromycin vs Pencillin V (1,102,419 prescriptions vs 7,364,292 prescriptions)

Primary Outcomes:

Cardiovascular Death

Results:

No increase in cardiovascular death with recent or past use of azithromycin
No increase in cardiovascular death in patients with no history of cardiovascular disease
There is an increase in cardiovascular death in patients with a history of cardiovascular disease

Limitations:

Did not have information of known risk factors for cardiovascular disease (smoking and BMI)
Number of events in the subgroup analysis is low

Conclusion:

Azithromycin use is not associated with an increased risk of death from cardiovascular causes in a general population of young and middle-aged adults

In my opinion, how will this affect your practice?

In the second study the patient population had better cardiovascular health than the first study
The increased cardiovascular risk may be from the systemic infectious process and not azithromycin itself
You can still prescribe azithromycin, but remember the small increased risk of death in patients with cardiovascular disease

References:

1. Ray WA et al. Azithromycin and the Risk of Cardiovascular Death. NEJM 2012: 366 (20); 1881 – 90. PMID: 22592294

2. Svanstrom H et al. Use of Azithromycin and Death from Cardiovascular Causes. NEJM 2013 May; 368 (18); 1704 – 1712. PMID: 23635050 _______________________________________________________________________________

Dr. Salim R. Rezaie is a physician at the University of Texas Health Science Center at San Antonio. He is double board-certified in Emergency Medicine and Internal Medicine.