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Azithromycin and the risk of cardiovascular death

Wayne A Ray1, Katherine T Murray, Kathi Hall

  • 1Division of Pharmacoepidemiology, Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. cindy.naron@vanderbilt.edu

The New England Journal of Medicine
|May 18, 2012
PubMed
Abstract

Insights

Azithromycin use, particularly in high-risk patients, is associated with a small but significant increase in cardiovascular deaths. This finding contrasts with the perception of azithromycin having minimal cardiotoxicity.

Area of Science:

  • Pharmacology
  • Cardiology
  • Public Health

Background:

  • Macrolide antibiotics, except azithromycin, are known to be proarrhythmic.
  • Published data suggest azithromycin may increase cardiovascular death risk, contrary to its perceived minimal cardiotoxicity.

Purpose of the Study:

  • To investigate the cardiovascular safety of azithromycin compared to other antibiotics and no antibiotic use.
  • To quantify the risk of death associated with short-term azithromycin therapy.

Main Methods:

  • A Tennessee Medicaid cohort study was conducted, excluding patients with severe non-cardiovascular illness.
  • Azithromycin users were propensity-score-matched with controls (no antibiotics), amoxicillin, ciprofloxacin, and levofloxacin users.
  • The study analyzed short-term cardiac effects and mortality risk.

Main Results:

  • Azithromycin use was linked to an increased risk of cardiovascular death (HR, 2.88) and all-cause mortality (HR, 1.85) compared to no antibiotic use.
  • Compared to amoxicillin, azithromycin showed increased cardiovascular death risk, with an estimated 47 additional deaths per million courses.
  • The risk was highest in patients with pre-existing cardiovascular disease.

Conclusions:

  • Short-term azithromycin therapy is associated with a small absolute increase in cardiovascular deaths.
  • This increased risk is most significant in patients with a high baseline risk of cardiovascular disease.

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