To the Editor: Azithromycin (at a single dose of 1 g) is one of two therapies recommended by the Centers for Disease Control and Prevention (CDC) for the treatment of chlamydia, and it is part of the regimen recommended by the CDC for the treatment of gonorrhea.1 Recently, Ray and colleagues2 reported an increased risk of death from cardiovascular causes associated with a 5-day course of azithromycin. This finding was not confirmed in a subsequent Danish study.3 Data are lacking on the use of azithromycin and the risk of death from cardiovascular causes among patients with sexually transmitted diseases (STDs).
We studied data from the Oregon Public Health Division on cases of chlamydia and gonorrhea in patients who received treatment between 1996 and 2012 and data from Public Health–Seattle and King County on cases of these infections in patients who received treatment between 1993 and 2010. We matched case-report data to death-record data (using Registry Plus Link Plus software4) to determine how many of these patients died within 10 days after treatment.
Cases of gonorrhea, chlamydia, or both in 269,179 patients were reported during the study period; complete treatment information was available for 260,048 of these patients (97%). Among the patients for whom data were available, 162,385 (62%) received azithromycin; among the 97,663 who did not receive azithromycin, the majority (77%) received a tetracycline. The mean age of the patients was 24 years, 65% were female, and 84% had chlamydia. We identified no deaths from cardiovascular causes among patients treated with azithromycin or another drug (Table 1). Five deaths that were not from cardiovascular causes were classified as being due to suicide (2 patients), homicide (1 patient), drug overdose (1 patient), and rectal cancer (1 patient).
Table 1.
Cumulative Incidence of Death among 260,048 Patients with Chlamydia, Gonorrhea, or Both, According to Prescribed Treatment (Oregon, 1996–2012, and King County, Washington, 1993–2010).*
| Deaths | Azithromycin (N = 162,385 |
Other Drug (N = 97,663) |
Relative Risk (95% CI)† |
|---|---|---|---|
| Cardiovascular cause | |||
| No. of deaths | 0 | 0 | Not determined |
| No. of deaths per 1 million doses (95% CI) | 0 (0–18.5) | 0 (0–30.7) | |
| Other cause | |||
| No. of deaths | 3 | 2 | 0.90 |
| No. of deaths per 1 million doses (95% CI) | 18.5 (3.8–54.0) | 20.5 (2.5–74.0) | (0.15–5.40) |
CI denotes confidence interval.
The group of patients who received other treatment was the reference group.
Our findings are consistent with those of the study by Svanström et al.3 that examined the association between azithromycin and the risk of death from cardiovascular causes among Danish adults between 18 to 64 years of age who had a low baseline risk of cardiovascular disease, but they differ from the findings in the study by Ray and colleagues, which included a substantially older population (patients who were 30 to 74 years of age) than patients who are typically treated for an STD (patients between the ages of 15 and 25 years).2 Of note, Ray observed only one death in 144,165 persons in the lowest four deciles of risk scores for cardiovascular disease (Ray W: personal communication). At that low level of risk (seven deaths per 1 million 5-day courses), we would expect only one death from cardiovascular causes associated with azithromycin use in our study population, and our study would have to involve more than 1 million persons to define the upper limit of the 95% confidence interval as being less than seven deaths per 1 million doses.
Our findings should be reassuring to health care providers who prescribe azithromycin to treat gonorrhea and chlamydia, and they support the conclusion of the CDC that research related to possible cardiac toxicity associated with azithromycin should not lead to a change in current treatment guidelines for STDs.5
Acknowledgments
Supported by grants from Public Health–Seattle and King County, the Oregon Public Health Division, and the National Institutes of Health (K23MH090923, to Dr. Dombrowski; and T32 AI07140, to Dr. Khosropour).
Footnotes
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.
Contributor Information
Christine M. Khosropour, University of Washington, Seattle, WA, ckhosro@uw.edu
Jeffrey D. Capizzi, Oregon Public Health Division, Portland, OR
Sean D. Schafer, Oregon Public Health Division, Portland, OR
James B. Kent, Michigan Department of Community Health, Lansing, MI
Julia C. Dombrowski, University of Washington, Seattle, WA
Matthew R. Golden, Public Health–Seattle and King County, Seattle, WA
References
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