Clarithromycin may be associated with increased risk for cardiac death

Clarithromycin may be associated with increased risk for cardiac death, although the absolute risk appears small, according to a new study.

Researchers in Denmark performed a nationwide cohort study using registry data to examine whether clarithromycin and roxithromycin were associated with cardiac death risk. (Both drugs are macrolide antibiotics, but only clarithromycin is available in the United States.) The study's main outcome measure was risk of cardiac death associated with each drug in comparison with penicillin V, which has no known relation to cardiac risk. The authors also conducted subgroup analyses by sex, age, risk score, and concomitant therapy with drugs that inhibit the cytochrome P450 3A enzyme and could therefore affect the way the body metabolizes macrolides. The study results were published online Aug. 19 by The BMJ.

A total of 5,104,594 treatment courses were included in the study, involving Danish adults from 40 to 74 years of age who were treated between 1997 and 2011. There were 160,297 courses of clarithromycin, 588,988 courses of roxithromycin, and 4,355,309 courses of penicillin V.

Overall, 285 patients died of cardiac causes, 18 during clarithromycin use, 32 during roxithromycin use, and 235 during penicillin use. The incidence rates for each drug were 5.3 per 1,000 person-years for clarithromycin, 2.5 per 1,000 person-years for roxithromycin, and 2.5 per 1,000 person-years for penicillin V. Adjusted rate ratios for clarithromycin and roxithromycin were 1.76 (95% CI, 1.08 to 2.85) and 1.04 (95% CI, 0.72 to 1.51), respectively. The association between clarithromycin and cardiac risk was stronger in women than in men (adjusted rate ratios, 2.83 [95% CI, 1.50 to 5.36] and 1.09 [95% CI, 0.51 to 2.35], respectively; P=0.07 for homogeneity). The adjusted absolute risk difference was 37 cardiac deaths (95% CI, 4 to 90) per 1 million treatment courses for clarithromycin and 2 cardiac deaths (95% CI, −14 to 25) per 1 million treatment courses with roxithromycin compared with penicillin V.

The authors acknowledged that they had no data on patients' lifestyle factors that would affect cardiac risk, such as body mass index and smoking status, as well as no information about the reasons why the drugs may have been prescribed, among other limitations. They also stressed that the clinical implications of their findings for individual patients are uncertain and that the absolute risk in their study was small.

“On the other hand, clarithromycin is one of the more commonly used antibiotics in many countries and many millions of people are prescribed this drug each year; thus, the total number of excess (potentially avoidable) cardiac deaths may not be negligible,” the authors wrote. “These factors need to be considered when assessing the overall benefit/risk profile of macrolides (clarithromycin specifically), an important area for future work by, for example, regulatory agencies and other public health officials.”