Azithromycin Benefits Outweigh MI Risks in Older Pneumonia Patients

Marlene Busko

June 04, 2014

DALLAS, TX — Among elderly, mainly male veterans hospitalized with community-acquired pneumonia, early survival benefits with azithromycin greatly exceeded risk of nonfatal MI, in a new study[1]. Specifically, within the first 90 days of hospitalization, treatment with azithromycin averted seven deaths for every nonfatal MI.

"This study supports the current Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines for community-acquired pneumonia that recommend the use of azithromycin as part of combination therapy for patients hospitalized with pneumonia," Dr Eric M Mortensen (Dallas VA Medical Center, TX) and colleagues write.

The findings confirmed that "there's definitely an advantage [with azithromycin] in terms of preventing death in community-acquired pneumonia, which is an often lethal condition," Dr Scott M Strayer (University of South Carolina School of Medicine, Columbia) agreed, in a comment to heartwire . The clinical implications are to "[make] sure that [patients] really do have a clear diagnosis of community-acquired pneumonia, and if they do have a history of cardiac disease or if they're sicker patients, really [make] sure that you are monitoring for any of these potential cardiac events and, if there are any alternative antibiotics that may be helpful, to consider them."

As reported by heartwire , Strayer and colleagues recently published a study from a cohort of veterans that showed that azithromycin significantly increased the risk of death and cardiac arrhythmia in the first five days of treatment. But in addition to the different timeframe, those veterans were slightly younger outpatients who were prescribed azithromycin for multiple indications, possibly inappropriately, since other studies have documented antibiotic overuse. The risk/benefit profile for azithromycin in the current study, which focused on this common, approved indication, is "reassuring," he noted.

The study was published in the June 4, 2014 issue of the Journal of the American Medical Association.

"Patients With the Most to Gain or Lose"

Pneumonia and influenza together are the eighth leading cause of death and the leading causes of infectious death in the US, the authors write. Macrolides are associated with improved survival after pneumonia, but they have been linked with CV risk. A 2012 study in a Medicaid population reported that azithromycin was associated with increased risk of cardiovascular and all-cause mortality within five days compared with amoxicillin or ciprofloxacin treatment—but that study did not document what azithromycin was prescribed for. In March 2013, the US Food and Drug Administration warned that azithromycin could potentially cause sudden death in people vulnerable to ventricular arrhythmia, such as those with preexisting QT prolongation, bradycardia, hypokalemia, or hypomagnesemia.

"Further research is critically needed to examine the safety of azithromycin inpatients hospitalized with community-acquired pneumonia, a group with potentially the most to gain or lose from its use," Mortensen and colleagues write.

Using data from the national Department of Veterans Affairs databases, they identified 73 690 patients from 118 hospitals who were 65 and older from 2002 to 2012 when they were admitted to the hospital for community-acquired pneumonia and received guideline-recommended combination antibiotic therapy—such as a fluoroquinolone or an appropriate beta-lactam, with or without azithromycin.

Primary outcomes were 30-day and 90-day mortality and cardiovascular events—MI, heart failure, and cardiac arrhythmia—within 90 days of admission.

The patients had a mean age of 77.8 years, and almost all (98.3%) were male.

The researchers analyzed outcomes in a propensity-matched cohort of 31 864 patients who had received combination therapy including azithromycin and 31 863 patients who had received other guideline-recommended therapy.

Ninety-day mortality was significantly lower in the veterans who received azithromycin compared with the others (17.4% vs 22.3%).

The veterans treated with azithromycin had a small, significantly increased odds of MI compared with those treated with other drugs (5.1% vs 4.4%). But they did not have a significantly increased risk of having any cardiac event (43.0% vs 42.7%), cardiac arrhythmias (25.8% vs 26.0%), or heart failure (26.3% vs 26.2%).

Positive Balance of Benefits vs Harms

"To put the balance of benefits and harms in context, based on the propensity-matched analysis, the number needed to treat with azithromycin was 21 to prevent one death within 90 days, compared with a number needed to harm of 144 for myocardial infarction," Mortensen and colleagues write. "This corresponds to a net benefit of around seven deaths averted for one nonfatal myocardial infarction induced."

Despite a potential increased risk of arrhythmias and MI, azithromycin lacks the appreciable drug-drug interactions seen with other macrolide antibiotics, and it is considered the safest of all macrolide antibiotics from a cardiac perspective, the authors write.

The beneficial effects of azithromycin and of macrolides in general for pneumonia may be due to their effect on immune function, they suggest.

Mortensen had no conflicts of interest. Disclosures for the coauthors are listed in the paper.

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