The antibiotic azithromycin, better known as the five-day “Z-pak,” typically does a great, and fast, job of combating such bacterial illnesses as sinus infections and bronchitis. But research published Wednesday evening in the May 17 issue of the New England Journal of Medicine finds that the drug is associated an increased risk of cardiovascular death.

The study notes that azithromycin has long been believed to pose no risk to the heart. But researchers at Vanderbilt University and the Nashville Veterans Administration Medical Center had seen a handful of reports of heart arrhythmias occurring among people taking the drug. To examine that potential link, they analyzed Tennessee Medicaid patient records from1992 – the year azithromycin was prescribed in the United States – to 2006. 

The study compared records for nearly 348,000 people who took azithromycin with records for people who took other antibiotics (including amoxicillin, which is used to treat the same infections azithromycin treats but is thought to pose no cardiac risk) and those who took no antibiotics at all. After controlling for confounding factors that might have contributed to cardiovascular problems, the researchers found a clear increase in risk of cardiovascular death among the Z-pak users compared to those on amoxicillin and those taking no antibiotics.

Folks taking azithromycin were at 2.5 times greater risk of cardiovascular death than those taking amoxicillin or those taking no antibiotic. That risk was elevated only during the five-day treatment period.

The overall risk of cardiac death was very small. Still, there were 47 more cardiovascular deaths per million courses of treatment among people taking azithromycin compared to the amoxicillin-taking group. And among people already at high risk for cardiovascular problems, that number rose to 245 added cardiovascular deaths per million.