Azithromycin not associated with increased cardiovascular risk in the general population

Azithromycin was not associated with an increased risk of death from cardiovascular causes in a general population of young and middle-aged adults, a Danish study found.

Researchers conducted a nationwide historical cohort study involving Danish adults in a registry database, ages 18 to 64, from 1997 through 2010. They estimated rate ratios for death from cardiovascular causes, comparing 1,102,050 uses of azithromycin to no use of antibiotic agents (matched in a 1:1 ratio according to propensity score) and 1,102,419 uses of azithromycin to 7,364,292 uses of penicillin V.

Results appeared in the May 2 New England Journal of Medicine.

Risk of death from cardiovascular causes significantly increased with current use of azithromycin compared to no antibiotic use (rate ratio [RR], 2.85; 95% CI, 1.13 to 7.24). There was no significantly increased risk with recent or past use. The risk of noncardiovascular death was also higher with current use of azithromycin compared to no antibiotic (RR, 1.60; 95% CI, 1.00 to 2.54).

However, when compared to penicillin V in an unadjusted analysis, azithromycin was not significantly associated with an increased risk of death from cardiovascular causes during current use (RR, 0.78; 95% CI, 0.47 to 1.28) or recent or past use. In an analysis adjusted for propensity scores, azithromycin was not associated with a significantly increased risk of death from cardiovascular causes during current use (RR, 0.93; 95% CI, 0.56 to 1.55), recent use (RR, 0.75; 95% CI, 0.34 to 1.62) or past use (RR, 0.92; 95% CI, 0.60 to 1.42) compared with penicillin V.

Researchers wrote, "[O]ur findings indicate that the risk of cardiac toxic effects associated with azithromycin may not be generalizable but may rather be limited to high-risk populations. The implications of these findings for clinical decision making are reassuring; they indicate that for the general population of patients seen in office practice, azithromycin can be prescribed without concern about an increased risk of death from cardiovascular causes, whereas the benefits of therapy need to be weighed against the risk of death from cardiovascular causes among patients with a high baseline risk of cardiovascular disease."

An accompanying editorial from the FDA noted that in March the agency revised the azithromycin product labels to reflect other study results that showed azithromycin can prolong the QT interval.

"Pharmacologic and epidemiologic data point to lethal arrhythmias as a potential consequence of QT-interval prolongation with use of azithromycin, other macrolides, and fluoroquinolones," the researchers wrote. "This possibility should give clinicians pause when they're considering prescribing antibacterial drugs, especially for patients with preexisting cardiovascular risk factors or clinical conditions in which antibacterial drug therapy has limited benefits."