Takeaway
- Outpatient azithromycin vs amoxicillin is linked to increased risk for cardiovascular (CV) death.
- Risk faded at 6-10 days after index date in this study of more than 7.8 million antibiotic exposures.
- The authors were puzzled by an additional association with short-term non-CV mortality, which, unlike the CV link, has no obvious mechanistic explanation.
Why this matters
- Azithromycin has made recent news for its use in combination with hydroxychloroquine for COVID-19, with the latter already implicated in CV problems.
Key results
- Within 5 days of the index date, azithromycin was tied to increased risk for CV death:
- HR, 1.82 (95% CI, 1.23-2.67).
- Adjusted risk difference for CV death:
- 12.79 (95% CI, 3.66-26.21) per 1,000,000 prescriptions.
- Risk for sudden cardiac death was not increased, however.
- At 5 days, azithromycin was also linked to increased risk (HRs) for:
- All-cause death: 2.17 (95% CI, 1.44-3.26).
- Non-CV death: 2.00 (95% CI, 1.51-2.63).
- These associations faded at 6-10 days.
Study design
- Retrospective analysis of 7,824,681 antibiotic exposures among 2,929,008 unique patients (mean age, 50.7 years) in 2 cohorts, from 1998 to 2014.
- Primary outcomes: CV death, sudden cardiac death.
- Funding: Pfizer.
Limitations
- Observational.
- Uncontrolled confounding likely.
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